NC_old229: Detection and Control of Porcine Reproductive and Respiratory Syndrome Virus and Emerging Viral Diseases of Swine

(Multistate Research Project)

Status: Active

NC_old229: Detection and Control of Porcine Reproductive and Respiratory Syndrome Virus and Emerging Viral Diseases of Swine

Duration: 10/01/2019 to 09/30/2024

Administrative Advisor(s):

NIFA Reps:

Non-Technical Summary

Statement of Issues and Justification

History of the group’s activities and its outcomes: Rationale for renewing this project for the period 2019-2024

When started in 1999, the newly formed NC 229 Multistate Committee first addressed the topic “Porcine Reproductive and Respiratory Disease Syndrome: Methods for the integrated control, prevention and elimination of PRRS in United States Swine Herds”. Since its very onset, the group has used a novel "consortium" approach to pursue stakeholder-driven major scientific goals on the virology, immunology, epidemiology, diagnostics and control of PRRSV, combining National Pork Board (NPB), industry and USDA funds.

Close to a decade later (on November 2008, on its way to this NC project’s third renewal), the NC 229 Committee was awarded the first annual Experiment Station Award for Excellence in Multistate Research by the Experiment Station Committee On Organization And Policy, conferred by The Board on Agriculture Assembly, of the National Association of State Universities and Land-Grant Colleges. The NC229 committee was commended because it has been a model of multistate collaboration between institutions, working with stakeholders and providing leadership in partnering with private organizations such as swine breeding companies, diagnostic and vaccine companies and the National Pork Board. (sic)  Typically this committee has been continuously very connected to stakeholders in the swine industry and stakeholder concerns are consistently addressed in the objectives of this project. The main reasons for such noteworthy distinction can be summarized as follows:

Throughout its existence, the NC-229 Multistate Committee has consisted of an important body of researchers that provides a forum for discussion and think-tank capabilities essential to coordinate strategies towards the control of PRRS and other major emerging diseases of swine, for example:

1. The NC-229 group of researchers has been the main driving force for the preparation and successful award of an initial USDA’s Coordinated Agricultural Project (CAP) in 2004-2008, which, following its renewal in 2010, led to the overall record achievement of almost $10 million dollars available for research, extension and education in PRRS and related diseases. The extraordinary significance of the NC-229-originated PRRS CAPs I and II , becomes clearly evident when it is taken into account that, combined with Check off funding provided by swine industry (NPB), brought a total dedicated to PRRS research to more than $34 million dollars distributed for creative research and extension within the last 19 years.

2. The NC-229 scientific meetings offered the appropriate forum and the foundation for the organization of an Annual PRRS Scientific Symposium that, although initiated first at a national level, grew to become a yearly event of major international scope known as the North American PRRSV Symposium. Such Symposium soon became also international in nature with two off-US venues already held in Asia, the first in 2013 and most recently 2018. To this end, the basic scientific organizational capacity of NC-229 was energized and materialized thanks to the financial backing secured through the CAP funds and later continued through support received from the swine, pharmaceutical and biologics related industries, to an extent such that in the most recent several years the NA PRRS Symposium became an event independent from NC229 and fully self-sustained at an exemplary level.

3. Since 2009, the NC-229 group expanded its goals beyond the topic of PRRSV to include other important swine emerging diseases. These additional important topics became an integral part of the program of annual symposiums of the NC-229 group, and proved to be of critical importance for those moments requiring making critical decisions, such as the successful realization that porcine circovirus associated diseases (PCVAD) can be controlled by effective vaccination, the identification/characterization of swine influenza isolates of importance to public health, and later on, the identification and quick adoption of diagnostic tools and appropriate disease management know-how in order to face the ongoing outbreak of porcine epidemic diarrhea virus (PEDV) in May 2013.

As an important spin-off of the increased awareness and expanded know-how on overall emerging swine diseases promoted by the scientific activity of NC229 group throughout the years, a very significant development took place in 2015 [during the lifespan of the ongoing NC229 project (2014-2019)] : the creation of The Swine Health Information Center (SHIC). Located in Des Moines Iowa the SHIC responds to a board of directors that represents the major commodity and swine practitioner organizations: NPPC and NPB as well as the AASV plus swine producers at large. The virtual initiator and current SHIC executive director is Dr. Paul Sundberg. The mission of SHIC is to protect and enhance the health of the United States swine herd through analysis of swine health data that would lead to coordinated global disease monitoring, preparedness and response. In other words the SHIC provides a systematic platform to approach the major viral disease threats affecting swine industry. Central to the preparedness proposed by the SHIC is the swine viral disease matrix developed by the SHIC. (see appendix A under attachments to this project). Such matrix is a dynamic and continuously updated list of major swine viral diseases ranked on average risk score based on 3 main criteria: 1) Likelihood of entry in the US 2) Economic effects on production post entry and 3) Effects on domestic and international markets. Undoubtedly, the research outcomes contributed by the NC229 community since its creation in 1999 have been central to the development of the SHIC swine viral disease matrix.  Likewise, such important tool should then constitute the actual road map for research work for the upcoming NC229 project for the next five years (2019-2024) which will be key for fulfillment of supreme goals set by SHIC for the swine industry: “monitoring, preparedness and response” (6)

Significance of the diseases we propose to study following the SHIC Swine Viral Disease Matrix:  

The overriding economic importance of PRRSV to North American agriculture, plus the significance of other emerging diseases represented for example by the permanent concern posed by swine influenza, the actual domestic threat presented by PEDV and other swine enteric coronavirues (SEDCV) or the very serious hazard represented by the presence of ASFV at the very doors of Europe and the Western Hemisphere while simultaneously expanding east bound in Asia thus threatening to become a globally expended disease (7), justify the continuation of this NC-229 multistate project. The intriguing and complex field of emerging viral diseases of swine surging and expanding in a planet with an ever-globalized economy does not allow us to let our guard down. Therefore, the designation of Detection and Control of Porcine Reproductive and Respiratory Syndrome Virus and Emerging Viral Diseases of Swine continues to be very current and appropriate for this project.

The need as indicated by stakeholders:

PRRS continues to be the most devastating disease of swine in the USA . While important advances have been achieved in control of this disease, some important obstacles still exist due to the unique immuno-pathogenic characteristics of this virus(5).  At the time the NC-229 2009 renewal, the swine industry remained burdened with the staggering $560-million price tag for production losses associated with PRRS calculated in 2005(3). In 2013, a more comprehensive and by now broadly accepted (and extensively cited) study (2) estimated that the total PRRSV tab to the industry was at $664 million annually, based on a review of production records from 80 breeding herds and grower pig closeout data on more than 600 groups of pigs over the past 3-5 years. Most importantly, the most current analyses also include expert opinions from more than 26 swine veterinarians who provide services to 2.4 million U.S. sows, which roughly represent 45% of the Nation’s sow herd. In addition, based on these experts opinion survey, animal health costs tack on another $140 million annually due to PRRS. The annual biosecurity and other outbreak-related costs attributed to PRRS were estimated to be $191.86 million and $145.82 million, respectively. Biosecurity costs include installation of air filtration systems, truck washes and other changes to transportation, added showers, changes in pig flow, etc. Total additional costs were pegged at $477.79 million annually, putting the cumulative cost of the disease at more than $1 billion/year when added to production-related losses. In addition, multiple sectorial studies in the US, Europe and Asia have further confirmed that infections by both types of PRRSV of different industry segments sustain the major important detriment of the global swine industry. Since its discovery in 1991, the PRRS virus has proven itself as a significant pathogen of swine in nearly all production areas of the world  (1). In 2006 it became apparent that strains of extraordinary virulence had surfaced in China, causing a major blow to the world’s largest swine herd. This threat and the general concern about virulence exacerbation by intense genome mutations in the field has reemphasized the need for effective PRRS control and the importance of finding predictably successful tools for managing or eliminating the virus from farms. The NPB, for the last 16 years, has been engaged in PRRSV area control and elimination efforts through research and education efforts that support and continue to develop tools and strategies to better manage the virus. The Swine Health Committee of the NPB has developed the following statement to help guide PRRS research and outreach efforts: By 2020, the National pork Board will deploy tools and programs to decrease the annual economic impact of PRRS by 20 percent, as adjusted for inflation and measured against the 2012 PRRS economic impact baseline study :

The national priorities for swine health research established by NPPC, NPB and American Association of swine Veterinarians (AASV), clearly characterized through the studies periodically released by the SHIC, constitute an accurate gauge of the stakeholder needs in the area of other important emerging diseases of swine of interest for the NC-229 committee. The NPB has announced, that there is an extreme need to assess the interspecies transfer of influenza virus (human to pig and vice-versa) and to assess the impact of vaccine interventions, such as vaccine use in people and pigs on the curtailment of transmission of influenza in farms and in exhibition settings and other points of concentration, with special emphasis on strategies to immunize young piglets that would circumvent the blocking caused by maternal antibodies(4). The NPB, and the AASV, backed by USDA/ APHIS have been following up the PEDV epizootics literally since the emergence of the index case and substantial emergency funds to support the most immediate needs in research have already been made available. Since then much has been learned about PEDV and other swine enteric coronaviruses in a relatively short amount of time. Additional questions remain about gilt development, potential long term effects of exposure and why some herds break back to active infection following a period of stability(4) . Regarding swine FAD particularly remarkable are the initiatives taken by stakeholders though NPB, SHIC  and USDA continuously since 2012 to respond to the threat posed by the extensive dissemination through Eastern Europe and China of African Swine Fever Virus (ASFV), The ASFV is considered by the US swine industry to be a major threat, to the point that the NPB and the competitive programs of USDA-AFRI, in a notable turning point, have been consistently funding projects based in local universities and other US academic laboratories associated with NC-229 in order to conduct investigations in this foreign disease. In the case of ASFV, the most recent priorities established by the US swine industry include  diagnaotics, disease mitigation, biosecurity, disinfection, and feed risk (4).

The technical feasibility of the research:

Successful realization of the study objectives requires basic and applied research studies, including immunology, functional genomics, epidemiology, genetics, and molecular biology. Within this framework, NC-229 has the capacity to coordinate ideas and resources, focus on specific problems and projects, and respond immediately to new information related to virus control and elimination. It has also provided a method of dissemination through coordinated national and international meeting forums. A well-documented record of such capacity of the group is represented by having attained and successfully managed two major CAP grants in PRRS and contributed to major international symposia in the US and overseas. This achievement attests to the expert technical know-how of the group. A remarkable spin off of the seminal funding obtained through the CAPs and post-CAPs federal and commodity group funding is represented by the continuous utilization by the group of CAP-generated results to amplify and leverage further funding through USDA NIFA competitive grants, NPB research grant program and industry funds.

The advantages of a multi-state research effort:

The NPB, NC-229 and other swine health experts have concluded that effective control of swine viruses will not rely on a single technology or solution, but on multiple strategies applied to all levels in the swine production system. While there is much expertise available from single entities, the best hope for the control and elimination of PRRSV and swine viral infections is a collaborative, multidisciplinary research program that focuses on specific aspects of the diseases. Progressively since 2008,  the NC-229 has been expanded to 14 stations (CT, GA, IA, IL, KS, MD, MO, MN, NC, NE, OH, IN, SD, and VA), 3 ARS labs (USDA-BARC, USDA-MARC, USDA-NADC), and importantly, international groups in China, Cuba, Russia, Mexico and Spain.

Likely impact of successfully completing the work: 

The greatest impact of the successful conclusion of this research will be new paradigms for the control of PRRS and other swine viral emerging diseases. Progress toward this goal will proceed through the successful accomplishment of specific aims and milestones described later in this proposal. The creation and operation of a virtual university environment where investigators share data and ideas has been effected by the previous PRRS CAP programs. A major milestone for this NC229 renewal will be to expand this network to address the real industry problem of complex swine viral diseases. A second milestone will be risk assessment projects that will demonstrate new protocols and management techniques for the control and elimination from the US Having multiple stations and researchers involved, will provide expertise in the vast array of viral diseases where knowledge in one area may translate to control in another. Therefore, not only is the NC229 consortium a multi-state multi-country multi-university group, but also a multi-pathogen related group. Communication across these collaborations will help in not only helping solve the current infectious disease problems, but also in being ready for the next emerging disease.

  1. Benfield, D. A., E. Nelson, J. E. Collins, L. Harris, S. M. Goyal, D. Robison, W. T. Christianson, R. B. Morrison, D. Gorcyca, and D. Chladek. 1992. Characterization of swine infertility and respiratory syndrome (SIRS) virus (isolate ATCC VR-2332). J Vet Diagn Invest 4:127-33.

  2. Holtkamp, D. J., J. B. Kliebenstein, and Collab. 2013. Assessment of the economic impact of porcine reproductive and respiratory syndrome virus on United States pork producers. . J. Swine Health Prod. 21:72-84.

  3. Neumann, E. J., J. B. Kliebenstein, C. D. Johnson, J. W. Mabry, E. J. Bush, A. H. Seitzinger, A. L. Green, and J. J. Zimmerman. 2005. Assessment of the economic impact of porcine reproductive and respiratory syndrome on swine production in the United States. J Am Vet Med Assoc 227:385-92.

  4. PorkCheckoff.b. 2018. Request for Proposals Swine Health -General Call – 2019.

  5. Rowland, R. R., and R. B. Morrison. 2012. Challenges and opportunities for the control and elimination of porcine reproductive and respiratory syndrome virus. Transbound Emerg Dis 59 Suppl 1:55-9.

  6. SHIC.a. 2018. Swine Health Information Center Progress Report 2017.

  7. SHIC.b. 2018. U.S. Pork Response African Swine Fever Prevention (September 10 2018).


Related, Current and Previous Work

Contributions of NC-229 investigators.

NC-229 was founded in 1999 as a vehicle to facilitate progress in Porcine Reproductive and Respiratory Syndrome (PRRS) virus research and promote collaboration and communication. During its first five years of existence, NC229 originally increased the participation of 8 state universities and USDA ARS labs, growing to 11 and 15 for the 2003/2008 renewals, while at the same time expanding the NC229 program ‘s research in order to include other emerging viruses of swine. For the 2014 renewal the number of units increased to 18 and finally now in 2018 we increase to  22 units, counting with the additional inclusion of several international sites (see updated Appendix E -2018) . Current participating institutions include 16 land grant universities plus other organizations such as ARS-BARC, ARS-NADC, ARS-MARC and foreign institutions in China, Cuba, Mexico and Spain. Scientists at the National Pork Board, USDA CSREES, and USDA APHIS are active participants. Representatives from a variety of industries (animal health and vaccine and diagnostic companies) and institutions continue to participate in NC-229 activities and meetings. The NC229 annual (public) meeting is being held in December of each year immediately prior to the Conference of Research Workers in Animal Diseases (CRWAD) to discuss research findings and plan future collaborative activities. Dr. David Benfield, Ohio State Univ., a pioneer in PRRSV research, continues to serve as the Project’s Administrative Advisor while also being Executive Director of CRWAD.

The NC-229 philosophy and approach to the topics of PRRS, other emerging viral infections of swine and respiratory disease issues is to address research problems that cannot be answered through traditional, single-investigator-initiated grants. The complexities of the problems addressed by NC-229 require a multi-state, multi-disciplinary, and multi-investigator research approach. The same philosophy and approach initially used to tackle PRRS is now transferred to the other urgent swine emerging infections, as a real threat (i.e.  PCV3, influenza, diverse emerging RNA viruses) or as an impending threat of monumental proportions (AFSV). In 2008 the National Association of State Universities and Land-Grant Colleges recognized NC-229 as the recipient of its first annual national multi-state research award, “for a project that best exhibits the ideals of multi-state research, such as high standards of scientific quality, relevance to a regional priority, multi-state collaboration, and professional leadership”. The Experiment Station Section Committee on Organization and Policy (ESCOP) Science and Technology committee served as the review panel. In essence, NC-229 activities are an embodiment of progress made towards understanding and eliminating PRRS and other major swine viral infections.

Examples of sustained endeavors by NC-229 participants include:

1. A history of extensive publication in the scientific literature on PRRS active until today. Since the time of the submission of most current NC229 renewal (Dec 2014) a search in PubMed indicates approximately a total of new 1030 PRRS-related publications. In all likelihood a substantial number of these publications were written by members of NC-229 institutions. A compelling proof of the current role of NC229 in producing new knowledge for the academic and professional community is represented by the sizable number of scientific reviews on the subject of PRRSV that have written by the NC-229 group within the last 4 years (2014-2018). Out of a total of 39 reviews written worldwide and covering different aspects of PRRSV, 27 of them have been written by researchers who have participated in NC229 in the immediate past and continue as participants in this renewal (1-23).

  1. Success with joint multistate proposals whenever made available by USDA or other agencies: The NC-229 group has been the generating and driving force behind the successful preparation of two multimillion dollar Coordinated Agricultural Projects (CAP) : 1) PRRSV CAP1: $4.4 million USDA NRI grant #2003-05164 on the Integrated Control and Elimination of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) in the U.S. and 2) the $4.8 million USDA NRI CAPs renewal grant #2008-55620-19132 on the Integrated strategies to control and reduce the impact of PRRS [PRRS CAP2]. Both PRRS CAP proposals dealt with complex collaborative research, education, and outreach plans via the coordinated efforts of the NC-229 multi-state consortium of PRRS researchers, academic institutions, USDA ARS labs, USDA-APHIS experts, the NPB, the American Association of Swine Veterinarians (AASV), and private industry.

  2. Collaboration with the swine industry in producer education and other special publications. The PRRS Compendium (ISBN 0-9722877-1-X), published in 2003 by the NPB, in two versions: one directed to researchers and another for industry and stakeholders. Includes chapters written by 12 authors from 5 NC-229 institutions. The NC-229 coordinated a special issue of the Journal of Veterinary Immunology and Immunopathology (volume 102 #3) on PRRS immunology and Immunopathology and the 2010 special issue of Virus Research on Progress in PRRS biology and control. More recently, the NC-229 edited, coordinated and provided authors for most of the chapters on swine viral vaccinology for a special issue of Veterinary Microbiology entitled “Advances in Vaccine Research against Economically Important viral Diseases (vol 206, July 2017 ISSN 0378-1135). In addition, it should be mentioned here that following the successful funding of CAP1 and CAP2, a PRRS CAP website was created which was later transferred to NPB; and NC-229 participants have been assisting in the sites management since then for many years. Such continuous drive to this type of multi-state/multi-investigator collaborative undertakings maintained by this NC229 group throughout the years should ensure the group’s readiness towards the CAPs RFP recently announced by NIFA for FY 2019 (24) It should be mentioned too that the NC229 research findings and outcomes has been a crucial support for the establishment of the Swine Health Information Center (SHIC). Located in Des Moines Iowa the SHIC responds to a board of directors that represents the major commodity and swine practitioner organizations: NPPC and NPB as well as the AASV plus swine producers at large. The mission of SHIC is to protect and enhance the health of the United States swine herd through analysis of swine health data that would lead to coordinated global disease monitoring, preparedness and response. (25) Finally Interactions with professional organizations, such as the AASV, and with scientists at the 1890s and 1994 land-grant institutions are permanent and enhanced through NPB outreach activities.

  3. The North American/International PRRS symposium constitutes a significant spinoff directly derived from the NC229. As a direct continuation of the initial NC229 meetings held around the CAP I, The North-American PRRS Symposia became an essential scientific communication instrument that complemented the basic research produced by NC229 with fundamental translational technology messages targeted to field practitioners, animal health decision makers and biologics companies Through the direct coordination of KSU by means of its faculty and continuing education division and in coordination with several other NC229 participating stations , the annual PRRS symposia became not only the most important annual national forums for the topics on swine virology but also acquired significant international projection, having successfully translocated the meeting overseas ( China) in two occasions : 2013 and 2018.

  4. Role of NC229 in other important forums for discussion of swine virology research: In addition of participating of the North American PRRS and Emerging Viral Diseases Symposium, the NC229 members have had active participation in the organization and delivery of highly successful scientific and continuing education events of significance for swine industry and US and international practitioners as well. Three major events should be mentioned in this respect: ISU’s swine conference John McKean Swine Disease Conference Symposium, the U MN Allen D. Leman Swine Conference Lehman, and its international counterpart: Leman China. Leman China deserves a particular comment, as it is an international event that has involved not UMN faculty but also multiple members of NC229 group. The Leman China Conference started in 2012 and this year was offered it 7th version. The conference presents the latest development on swine research and production, disease surveillance and control, integration of production and public health, and their impacts on the global economy to China, which is the world's biggest pork-producing country.

  5. Successful pursuit of competitive grants to support PRRSV and swine respiratory disease research in general. In addition to the PRRS CAP I & II grants (which served for many as actual seed funding for future competitive successful research funds) , numerous industry grants and contracts have been awarded to NC-229 participants for pig respiratory disease research (not only for PRRSV but also including other infections such as swine influenza virus, PCV2, PEDV) for the last 15 years . Likewise, several laboratories were awarded competitive funds made available by NPB to respond to the emergency posed by the appearance in the US, during the spring 2013, of PEDV. Likewise selected laboratories located in Mid-West (and other non-PIADC areas of mainland US) have received funding for ASFV. A particular mention deserves KSU where the presence of a BSL3 facility for large animals has been implemented, thus allowing for experiments with foreign swine pathogens as ASFV and CSFV. All those labs recently awarded funding on emerging viruses of swine are herein represented in this submission for renewal. Most importantly, it should be mentioned that during the last five years different participants of NC229 were awarded 28 competitive USDA-AFRI-NIFA grants or NIH R21, amounting to a total of $ 10,698,120, thus exceedingly more than triplicating the amount granted to the entire last CAPII during the same period of time. Listing of the federal competitive funding (USDAAFRI NIFA or NIH) awards received by the NC-229 community during the last five years is attached as Appendix A.

How Hatch funds assigned to experimental stations participating of NC229 help to leverage the above external competitive funds obtained by NC229: Over the twenty-year history of NC229 there has been a perceptible change in how experiment stations have assigned Hatch funds to promote multi-station research through NC229. Before, a vast majority of participating stations followed a traditional model for fund distribution basing allocations on university-based strategic goals and needs, and were split among departments, farm/animal research units, and other field stations using a formula-based approach. This distribution method typically provided for a discrete funding amount per investigator or station representative to cover travel costs for participation in the annual NC229 meeting. Now, as NC229 started producing major external competitive research grants (i.e. CAP I awarded in 2004), many of the participating stations have switched to more competitive internal allocation methods with the goals of promoting research excellence , generating high quality preliminary results and securing  competitive federal research funding. The approaches taken have varied broadly amongst stations. For example, at the U of MD proposals are encouraged to focus on and specifically address NIFA’s priority areas, under both Foundational and other AFRI programs. In some cases, the RFPs for internal competition for Hatch funds are targeted on promoting interdisciplinary teams that will be competitive for federal funding (U of NE). In other cases such as U of MN, funding is targeted toward generating high quality results to enhance opportunities for external funding coming from federal, foundation or industry. In many cases like U of NE the RFP specifically requires participation by the PI in one NC project. In all cases, funding selection depends on rigorous scientific review accomplished by internal faculty of the respective universities or by scientific reviewers from external institutions.

  1. Successful Outcomes in Intellectual Property that have derived from NC229 research: Patents and intellectual property claims constitute a significant parameter to gage the long term impact of the scientific innovation produced by the NC229 group. Collectively the group produces, year after year, a number of intellectual property claims and patents which are currently at different levels of approvals. For a complete list of these achievements we refer the reader to the attached copies of the NC229 annual reports for the last 5 years (See annual progress reports in NIMSS). Nonetheless it is particularly important to mention here a few examples of patents representing inventions carried out by NC229 researchers that currently have reached the stage of being implemented, marketed or firmly explored by industry such as:

1) US Patent # 9457074 granted on April 14, 2015. “Compositions and methods for treating and preventing Porcine Reproductive and Respiratory Syndrome.”  Inventors : Renukaradhya, G J, Dwivedi, V, Binjawadagi, B, and Torrelles, J B. (OSU) Technology licensed to company for manufacturing a novel mucosal vaccine that has been in the market since February 2017 ; 2) Provisional US patent application, #62/166,344, filed on June 2016"Nanoparticle based vaccine strategy against swine influenza virus." Inventors: Renukaradhya G J, Dhakal, S, Hiremath, J, and Lee, C W.(OSU)  Technology licensed to a company3) US Patents: 8,663,984; 9,149,518 “ZMAC technology (porcine alveolar macrophage cell line)” inventor: Zuckermann F (UIUC) technology licensed to a company to manufacture the mucosal vaccine cited above, 4)  US patent 10,072,046, issued Sept 11, 2018. “A non-naturally occurring porcine reproductive and respiratory syndrome virus (PRRSV) and methods of using” Inventors: Vu, H, Osorio F, Pattnaik AK, Fa, M (UNL) technology licensed to vaccine company that is exploring its use in a new live attenuated vaccine

NC229 Project Current Research Background: Many of the important challenges that PRRSV presents to the animal health community are based on the unique biology of the infection that this virus establishes in a pig. Many of the pathogenic events that occur during a swine infection by PRRSV have been characterized by NC-229 participants. After exposure to PRRSV, a prolonged, acute productive infection takes place, characterized by viremia that may last up to 30 days post-infection or more. PRRSV begins to be (slowly) eliminated from the host when PRRSV-neutralizing antibodies and cell-mediated immunity appear. Remarkably at odds with the kinetics of host response observed in the case of other swine viral infections, this incipient anti-PRRSV protective immunity begins not earlier than 4 weeks p.i. and meagerly builds up during the ensuing weeks. There is an evident inability of the host to clear PRRSV, likely explained by the different mechanisms that PRRSV employs to evade the immune response. Those mechanisms may include: replication and destruction of the cell that is main viral target : the macrophage, a major player within the immune system, ensuing cytokine storms, selective destruction of innate immunity mediators, display of decoy epitopes in structural proteins, shielding by glycans of meaningful neutralizing epitopes, and significant genetic variation, that translates into significant antigenic variation. As a consequence of these viral strategies, a persistent phase of infection follows the acute period of infection. In this late infectious phase, PRRSV persists at lower load levels in selected sites of the body, primarily lymphoid tissue. The persistence of PRRSV involves a continuous low level of viral replication but not as a true steady-state persistent infection. Indeed, the PRRSV persistent infection is eventually cleared (after several months), implying an eventual recovery of immune competence and establishment of a robust immunological memory, which is effective in preventing re-infection by homologous or closely related PRRSV strains but that can be circumvented by less cross-protective, more heterologous PRRSV strains. The most common approach to control PRRSV infections has been the use of vaccines. Different types of vaccines are in use, with the modified live strains being considered the best standard of efficacy at this time. However, the significant antigenic variation exhibited by the multiple strains of PRRSV translates in a moderate to poor efficacy in preventing infection with strains that are less related to the vaccine strain. Therefore, an effective heterologous protection to broaden the protective spectrum of vaccines is the foremost challenge to be resolved in PRRSV vaccinology research, whatever the type of vaccine or platform.

A major new approach to control PRRS infections has been proposed now based on studies of genetic resistance to disease through the continuous study of the swine genome that has been concluded and perfected thanks to a large team of researchers including many participants of NC229. The objective of this novel line of studies is now to identify genes, mutations and pathways that could predict genetic susceptibility to PRRSV. A very compelling proof of success in controlling PRRSV following genetics has been the extraordinary advance produced through genetic modification of the swine germ line and creation of PRRSV resistant pigs by ablation of expression of the main receptor that permits entry of PRRSV in swine macrophages: CD163. Several NC229 labs, led by the group at KSU, are actively approaching this route, by studying not only the optimization of the genetic manipulation of the genome to ensure strict resistance to PRRSV but also to study the impact that this modification may have on the pig’s homeostasis seeking an harmonization of disease resistance status with high production profile of the pig. 

Throughout the life of NC-229, the NC229 researchers have been tackling these and other fundamental problems posed by PRRSV to better understand the mechanisms and tools required to efficiently control PRRSV infections in the field. Since the expansion, a decade ago, of the scope or research conducted by NC229 researchers to other emerging and re-emerging viral infections of swine, the research agenda of the group became more dynamic, complex and diversified to respond to the urgent animal health needs related to important infections in the swine industry (both endemic and exotic threats). Such diversification can be appreciated in the assembly of the second objective of this new proposal which has now has been divided in eight different sub-aims related to the diversity of viruses impacting the swine industry. (See Objective 2.1 to 2.8)

By way of example of current and ongoing productivity of NC-229 we can list the following outcomes reported by different laboratories within the NC-229 in their search for solutions for PRRSV and other viral infections. These should not be envisaged as a complete list of achievements made by NC-229 in the last 5 years. The following topics, instead are individual examples taken from the most recent NC229 annual report (December 2017) which currently (NC229 2014-2019) includes only two objectives.


  1. Objective 1: The first overall objective for this five-year NC-229 project (2019-2024) is to reduce the impact PRRS has on producers, and to assess the feasibility and financial acceptability of PRRS area control and/or elimination for producers. To that end, we commit to focus on at least the following 3 firstpoints, which represent the current research priorities of the US swine industry as defined by the NPB 2018 call for research priorities.
    Comments: 1.1. PRRS immunology/vaccinology: Swine industry views as significant impediments to achieving the PRRS reduction goal being : the frequent re-breaks of clinical disease in PRRS Stable Farms,” and the constant need for safer and more efficacious vaccines. Central to this problem is the perfection of current vaccine towards broader antigenic coverage of the diverse strain circulating in the field. Likewise reduction in disease incidence will be dependent in part on highly sensitive diagnostic assays/methods . 1.2. PRRS epidemiology: Developing an understanding of the epidemiology of contemporary viral strains circulating in the field is critical to reduce between-herd transmission and minimize the average time-to-stability of herds following outbreaks. Current herd closure and management recommendations affecting average herd time-to-stability needs to be evaluated through a coordinated investigation of the relationships between the characteristics of the contemporary PRRSV strains, the host response and environmental factors. Central to these studies are perfected rational biosecurity measures including studies drivers of PRRSV circulation to be enhanced through data-mining large datasets. 1.3. PRRS Surveillance and Diagnostics: The development of effective testing and surveillance strategies supports the goal of reducing the impact of PRRS by 20% as well as support the future programs for the elimination of the virus. New tools and strategies are needed in order to effectively reach this goal. Accurately defining the true PRRS status of a site will have greater importance as the incidence of PRRSV decreases with success of the 2020 program and beyond. Novel cost effective ways to monitor populations should be considered in terms of sample types, procedures and target populations . 1.4. PRRSV Genomics: The genome varies considerably between and within Type 1 (European-like) and Type 2 (North American-like) PRRSV. The continued discovery of new viral strains and their genetic components, how these components vary, and the cellular functions associated with this variation is crucial to unraveling this complex pathogen and providing improved diagnostics, surveillance and vaccines.
  2. Objective 2 Developing effective and efficient approaches for detection, prevention and control of pressing viral diseases of swine of recent emergence.
    Comments: Pestiviruses: CSFV DIVA tests are pursued at UCONN for new live attenuated vaccine developed at PIADC and at KSU for E2 subunit vaccine and for pigs vaccinated with CSFV China strain. Senecavirus and other newly emerging pathogens: Several diagnostic tests for new emerging pathogens such as atypical pestiviruses, Seneca virus, porcine circovirus 3 have been developed (KSU, SDSU, and ISU). New monoclonal antibody-based reagents for Senecavirus A and a fluorescence-based virus neutralization assay for the detection of neutralizing antibodies is now offered as a diagnostic service (SDSU). ASFV: A systematic immunogenic study of different ASFV antigens cloned in adenovirus vectors are being evaluated in pursuit of developing a protective ASFV subunit vaccine (KSU). This is crucial for protection of the US swine population given the rather rapid spread of ASFV in China and the risk of introduction into the US through world trade. Foreign Animal Disease (FAD) import risk: An exemplary multi-laboratory collaboration that responds to the true essence of NC229 group, Pipestone Applied Research (MN) ISU, SDSU, KSU have jointly undertaken, with collaboration with SHIC and support of NPB, a significant experiment to test the risk of importing FAD through contaminated feed ingredients, using high consequence pathogens and surrogate viruses and simulating shipment conditions from China to the US. Results demonstrate the ability of multiple viral pathogens to survive in certain feed ingredients, including soybean meal. This study suggests that contaminated feed ingredients could present transboundary risk factors for high consequence pathogens. A major outcome of this project has been the resulting publication (27) that is being highly cited. Swine Influenza Virus: Epidemiology studies based in UMN , NADC, ISU focus on studies of the seasonality of influenza A in farms, impact of climactic conditions on infection at weaning, co-circulation of multiple genome constellations, routes for virus introduction and persistence in pigs, studies centering primarily on piglets as a source of diversity


Objective 1 (Control of PRRSV)

Sub objective 1.1) PRRSV Immunity and Vaccinology: The strategy in PRRSV vaccinology should continue to be centered, during the next five years, on increasing the understanding of correlates of immunity and mechanisms to broaden protection (UMd, Ohio, UNL, VTech, UConn , UMN, UIUC, SDSU,BARC/ARS,NADC/ARS, ISU, KSU). This objective addresses PRRSV vaccinology research related to development of new generation vaccine formulations, and their evaluation in pigs based on understanding the immune correlates. Particular emphasis is being given (UNL, KSU, UMD, UCONN) to how PRRSV immunization can stimulate innate immunity (i.e. IFN), early in infection, to consequently secure a stronger acquired immunity. Identifying the strategies by which the efficacy of modified live (PRRSV-MLV) and inactivated PRRS virus vaccines induced immune responses can be improved, and in design of alternate approaches to effectively control PRRS and reduce its transmission in swine herds:  (i) Identification of ideal PRRSV strains to use in new generation vaccines. Since 1991 strain VR2332 is commonly used in the production of PRRSV-MLV vaccine, but a compelling need felt by producers and practitioners is to produce vaccines that correspond to PRRSV strains circulating in the field. Further research is warranted to evaluate other available PRRSV strains to use in the design of better vaccine candidates. An ideal strategy appears to be the design of genetically modified PRRSV vaccine by reverse genetics, which is devoid of immunosuppressive properties and can elicit enhanced cross-protective immunity in pigs. The methods adapted to evaluate the ideal PRRSV strains to use in future vaccine formulations include, both in vivo studies in pigs and in vitro studies using appropriate cell lines and primary target cells. As the PRRSV basically has inherent immune modulating properties, generation of a genetically modified virus which overcomes the immunosuppressive properties appears to be advantageous: (ii) Development of stable pig cell lines for vaccine development and immunological studies. Lack of a stable permissive pig cell line to propagate PRRSV in vitro in a more natural atmosphere was overcome with the development of a porcine alveolar macrophage cell line, ZMAC. This cell line could serve as a platform to develop more successful vaccines. Currently ZMAC is being explored by biologics companies as to its utilization as a platform for virus production.  It is very important to develop multiple PRRSV permissive cell lines, either through transfection of virus receptive receptors on existing pig cell lines or through immortalizing the permissive pig macrophages. This is important because, PRRSV infects only a particular subset of macrophages. There are several methods to immortalize cells, such as chemicals, viruses, genetic manipulations etc. (iii) Detection of tools to rapidly measure the degree of antigenic diversity in field PRRSV isolates in relation to current vaccine strains, and identification of immunodominant PRRSV T and B cell epitopes of both structural and non-structural viral proteins. The identified epitopes may be important for the formulation of immunogens (i.e. peptide vaccines) to provide broad cross-protection against diverse PRRSV strains. To make steady progress in development of innovative PRRSV vaccines, we need to have a cost-effective tool to constantly monitor the genetic diversity of new PRRSV field isolates, especially detected in vaccinated swine herds. A recently reported alternative (UNL) to develop synthetic consensus strains by alignment and analysis of multiple full genome sequences has been successful and continues to be explored and transferred also to the swine influenza model. Interestingly, the consensus attenuated vaccine is one of the strains that are used as proof-of-concept of the ability of PRRSV immunogens to induce IFN resulting in a broader solid protection. Several studies on virulence markers for PRRSV (KSU) have derived interesting concepts that can be applied to the creation of new attenuated vaccines. Particularly important is the mechanism of replication causing -2/-1 ribosome frameshifting of the NSP2 nonstructural viral gene that has proved to be a principal marker of virulence and at the same time provide the key for rational attenuation of selected strains thus leading to a rapid development of new vaccines. Discovery of T and B cell epitopes on PRRSV predicted using computer based logarithmic approaches should be confirmed in functional studies using pig immune cells isolated from repeatedly vaccinated and/or infected adult pigs. Generation of CD163 receptor knockout pigs by genetic modification of the germline (U of Mo/KSU) provided a formidable tool to unequivocally demonstrate genetic resistance to PRRSV and at the same time provides a useful tool to better understand which PRRSV proteins moieties interact with CD163 and which are good candidates to be broadly protective epitopes on PRRSV.  Advancement in the understanding of neutralizing antibody responses of swine to PRRSV and variation in individual animal responses is expected to provide new opportunities for genetic improvement of resistance to PRRSV as well as in the area of mechanisms of protective immunity (UMN). While live attenuated vaccines seem to be so far the most effective means to immunize against PRRSV, the concern of reversion always exists. It is important to develop innovative killed PRRSV vaccine delivery system which elicits enhanced and heterologous cross-protection Thus, considering the widespread prevalence of PRRS virus in the US, developing an innovative inactivated PRRSV vaccine using the alternate delivery methods should be a priority. In that direction, nanotechnology based inactivated PRRSV vaccine has showed good promise. Additional promising tools that will be tested are new viral vectors (U of GA/KSU) such as swine parainfluenza PIV5 to produce effective subunit vaccines. 

Sub-objective 1.2) PRRSV Epidemiology: Developing an understanding of the epidemiology of contemporary PRRSV strains circulating in the field is critical to be able to minimize the average time-to-stability (stabilizing the spread of PRRSV within a herd and increasing the time to clearance of the virus in the herd) of herds following outbreaks. Current herd closure and management recommendations affecting average herd time-to-stability need to be evaluated through a coordinated investigation of the relationships between the characteristics of the contemporary PRRSV strains, the host response and environmental factors.

Quantifying the association between epidemiological factors and PRRSV incidence is prerequisite for developing predictive models of PRRSV spread through systems and regions (UMN).   Molecular understanding of age-dependent resistance to PRRSV may lead to improved immunological tools for stimulation of PRRSV resistance and improved vaccine prevention. Improved methods forecasting outbreaks of PRRS related to movement of swine between and within herds using dynamic network analysis to identify the farms that are super-spreaders. Following the method to apply data on pig movements, geolocation of farms, environmental and weather factors, machine-learning algorithms to forecast the probability that a sow farm will become infected with PRRSV. Identifying and targeting super-spreader farms allows to prioritize resources to control disease. 

Sub-objective 1.3) PRRS surveillance and diagnosis:  The development of effective testing and surveillance strategies should support the goal of reducing the impact of PRRS by 20% a goal set by NPB’s swine health committee for the year 2020, as well as support the future programs for the elimination of the virus. New tools and strategies are needed in order to effectively reach this goal. Accurately defining the true PRRS status on a farm site will have greater importance as the incidence of PRRSV decreases with success of the 2020 program and beyond.  Simpler faster more accurate tests are required. Rapid point of care test may become very useful sometime in the near future. Amplification at point of care will be tested (ISU, KSU, UMN) using an rRT-PCR system as the gold standard to compare new nucleic acid analyzer PCKIT with the goal of adopting it as a test that can be used at or near points of need (farms). KSU already promotes the use of a Luminex for PRRSV strain differentiation by a colorimetric assay, which should constitute information of the upmost importance. Beyond control, the only way that vaccination could become compatible with eradication is by developing a vaccine compatible with a DIVA (differentiating infected from vaccinated animals). DIVA marker development is ongoing at several stations (UNL,NDSU,KSU): In the case of living, replicating vaccines, the methodology to follow will likely concentrate on finding ideal serologic markers that would be: 1) frankly immunodominant, 2) a peptide or part of protein that is not involved in protective immunity, 3)negligible without compromising virus viability ( in order to fulfill the requirement of being amenable to deletion, thus empowering the vaccine with negative marker potential) and 4) to be extremely well conserved so that most if not all the animals infected with the vast majority of wt PRRSV strains can develop antibodies to these candidate serologic markers. The experiments will, in the case of live virus vaccines, be based mainly on reverse genetics methodologies. Stability of the DIVA strain developed this way should be measured in vivo and by means of virological and serological parameters. The regular N antigen ELISA will be considered the default DIVA markers in the case of all the possible sub-structural (subunit) vaccines, which most likely will be formulated with one or more glycoproteins or other PRRSV envelope proteins.

Objective 2. Developing effective and efficient approaches for detection, prevention and control of pressing viral diseases of swine of recent emergence.


Sub objective 2.1 ASFV: Vaccine Design and Development - (UIUC, KSU, CT, Plum Island Animal Disease Center, ARS, USDA and National Research Institute for Veterinary Virology and Microbiology, Pokrov, Russian Federation). ASF is arguably the most significant emerging disease threat for the swine industry worldwide. Devastating ASF disease outbreaks and the continuing disease epidemic in the Caucasus region, Russia, Eastern Europe and most recently overall China and Western Europe (Belgium 2007 to date) highlight the significance of the threat. There is no available vaccine for ASF, however, it is clear that vaccination is possible since protection against homologous re-infection has been definitively demonstrated. Vaccine progress is hindered by the fact that the extent of ASFV strain variation and variability and the viral antigens responsible for protective immunity remain unknown The overall goal of work outlined in this objective is to provide critical foundational information on ASFV strain variation and identify viral protein(s) associated with protective immunity, thus enabling rationale for ASFV vaccine design/development. The availability of effective ASF vaccines will significantly reduce the disease risk for US agriculture and food systems. Define ASFV strain diversity and identify genetic signature(s) for ASFV serologic group specificity/cross protective immunity - Knowledge of ASFV strain diversity and the breadth of strain variation in nature, and notably diversity of relevant protective antigens, will enable development of rapid genotyping methods capable of discriminating among viruses of specific serotype and predicting efficacy of a given vaccine for an outbreak field strain. Better understanding of diversity among protective antigens will also facilitate design and development of more efficacious immunogens. Comparative ASFV genomic analysis will be used to identify genetic signatures of viral proteins that correlate with the serogroup/cross protective immunity and signatures modeled to provide power in prediction of biological serotype specificity based on sequence information alone (KSU). Available collections of ASFV isolates will be evaluated to better define the extent of virus variation in nature. Identify ASF viral protein(s) responsible for protective immunity: Identification and prioritization of ASFV protective antigens will permit development of subunit-vectored vaccines and rationally engineered live-attenuated vaccine candidates that will be DIVA compatible and suitable for use under emergency conditions in non-endemic countries such as the United States. Putative ASFV protective antigens (PA) will be identified and evaluated using ASFV chimeric and/or gene-deleted viruses or other gene delivery vectors in vaccination/challenge experiments in pigs. Host responses correlated with protection will be identified. PAs will be prioritized and the most promising candidates evaluated further as vectored subunit antigens in vaccination/challenge experiments in pigs.


Sub-objective 2.2: Swine Influenza Virus: (UMN, UGA, IA, IL, KS, OSU, SDSU, USDA/ARS-NADC) In this objective, factors influencing influenza virus transmission within and between swine farms will be determined to reduce economic losses caused by this disease. Identifying the mechanisms by which these pathogens enter, circulate and persist in swine herds is a critical step to devising methods that effectively prevent, control and/or eliminate this virus. The relationships between virus diversity and evolution with the ecology, epidemiology, and virulence properties of influenza A (IAV) virus in swine will be investigated, including viruses from under-sampled pig populations in North America, at local, regional or national scales. Epidemiologic and ecologic factors such as production system type, population immunity, age of susceptibility, seasonality, and polymicrobial interactions will be assessed to determine how influenza viruses are introduced and persist on farms and how are they moved within and between production systems and globally. The genetic or genomic bases for viral fitness or virulence will be investigated.  The effectiveness of current and novel practices for preventing IAV infection will be evaluated, identifying immune parameters that are correlates of heterologous protection with traditional and/or new vaccine platforms or evaluating new vaccine strategies such as those targeting different age groups or seasonal whole-herd vaccinations versus vaccinating breeding animals on production schedules. Proof of principle that centralized antigen concept can be applied to develop a protective vaccine against SIV: The extent that genetic diversity impacts antigenic diversity and suboptimal immunity contributes to evolution of influenza viruses in swine will be evaluated. Alternative interventions to prevent new introductions to swine herds will be investigated. Impact of influenza A at the human-animal interface: The impact of human to swine, swine to human or other risk of interspecies transmission of IAV to swine will be assessed to define the ecological and genetic determinants for human seasonal viruses to periodically transmit to swine, the adaptations required for sustained transmission of human or avian viruses in swine, if humans can be asymptomatic carriers of swine influenza and contribute to the movement of swine influenza viruses, the risk factors for zoonotic transmission of influenza from swine to humans, and the genetic determinants or adaptations required for sustained transmission of swine viruses in humans.

Population studies in different age groups will be conducted to explain the transmission and control of swine influenza virus under the hypothesis that the piglet plays a central role in this transmission (UMN), because weaned piglets are the source of strain diversity reservoirs of influenza at a subclinical level. The goal in this study should derive a combination of practices that increase the resistance of pigs from getting infected and practices that decrease risk of exposure to SIV, which is an essential part of influenza control prior to weaning.



Sub-objective 2.3 Porcine Circovirus:  Porcine Circovirus 2 serves as a well-known model of an efficient non-replicating immunogen for swine. The first successful vaccine against PCV2 was a chimeric construct between the non-pathogenic PCV1 and the pathogenic PCV2. The lead laboratory in this research (VTECH) will now evaluate the potential use of the non-pathogenic PCV1 as a vaccine delivery vector against other swine pathogens such as PRRSV and also a dual vaccine anti PRRSV and PCV2. Extensive evaluation of cross protection in vivo should be conducted to ascertain if it is necessary to vaccinate against the new genotype PCV3.


Sub-objective 2.4 Swine Pestiviruses: Emphasis will be on developing DIVA vaccines for CSFV:  either as a subunit (E2) vaccine (KSU) or by deletion of peptide marker in E2 to provide a marker candidate live attenuated vaccine (developed at PIADC) with a DIVA assay (UCONN).



Sub-objective 2.5: Senecavirus:  Comprehensive studies to characterize the pathogenesis and immunity to SVA infection will be conducted (SDSU). Additionally, diagnostic assays and reagents (a new monoclonal antibody-based reagent for Senecavirus A and a fluorescence-based virus neutralization assay for the detection of neutralizing antibodies) in progress (SDSU).  ISU is investigating Seneca virus immunopathogenesis, specifically the upregulation of pro-inflammatory cytokines in in cell culture and in vivo.


Subobjective 2.6:  Sapelovirus:  The goal of these studies is to determine whether astrovirus or sapelovirus each alone or in association are etiologic agents of polyencephalomyelitis of swine (see sub-objective 2.6 also, ISU).


Sub-objective 2.7: Viruses with potential interest to Xeno-transplantation science: Pathogenesis of Torque teno virus, a swine model for human infection with TTV (ISU, NDSU).  The prevalence of porcine torque teno virus (TTV) in the worldwide swine population is high and most farms are TTV positive. Evidence from the field indicates that TTV infection may be linked to multisystemic disease processes in swine as the incidence of TTV DNA in sick pigs is higher compared to that of healthy pigs. It is known, that TTV can be demonstrated in bone marrow of infected pigs; however, the exact role of TTV in swine disease pathogenesis remains to be determined. Recently, the TTV DNA positive status of pigs has been linked to reduced vaccine efficacy (particularly PRRSV vaccine) under field conditions. If this is true, TTV could be having more of an impact on swine health than currently thought. The role of TTV needs to be further investigated (ISU)  


Measurement of Progress and Results


  • Data published in peer-reviewed scientific literature, as well as data and interpretations published in industry newsletters and other publications targeted to the swine industry and allied providers. Given the significance of the focused objectives adopted by NC-229 in this proposal we anticipate that the rate of data produced will be consistent with or even higher than the productivity demonstrated by NC229 throughout the last 15 years.
  • Continue the number and quality presentations at meetings, workshops, and symposia attended by swine veterinarians and members of the swine industry. These include the annual International/North American PRRS Symposium, the Annual NC229 meeting and CRWAD swine diseases and viral pathogenesis sessions, as well as meetings of the American Association of Swine Veterinarians, the International Pig Veterinary Society, the Iowa State University Swine Health Conference, the Allen D. Leman Swine Conference and Leman China
  • Maintain cross-talk and increase partnership with NC-229 equivalent groups in other countries and continents ( i.e. COST Action network, Simposio Internacional PRRS Mexico, AMVEC Mexico etc.)
  • Continue expansion of standard methods, protocols, and reagents for serological, immunological, and virological assessments of virus-host swine interactions.
  • Continue educational and training manuals, CDs, pamphlets and literature related to biosecurity, biosecurity implementation and biosecurity monitoring.

Outcomes or Projected Impacts

  • Production of value-added swine and pork products through the diagnosis and control of PRRSV and emerging viral disease in breeding herds and genetic stocks
  • Increased global competitiveness of the U.S. swine industry by eliminating the cost of PRRS and by producing PRRS-free pigs.
  • Lead the worldwide research community towards the concept of a feasible immunization strategy against ASFV targeted to endemic areas of the world.
  • Prevent the introduction of ASFV in North America. Develop and increase preparedness.
  • Improved food safety by elimination of disease agents most impactful on health in swine, including PEDV and influenza.
  • Outcome/impact 6: Promotion of greater harmony between agriculture and the environment by the development of more efficient and sustainable swine production practices through elimination of the most significant health hazard to swine.
  • Sustainable swine production through improved disease prevention and control strategies.
  • Promote food security through prevention and control of viral disease pathogens that pose significant burden to the industry.
  • Increased preparedness of the industry to emerging swine diseases circulating worldwide.


(2019):Please refer to attached Appendix B for milestones document.

Projected Participation

View Appendix E: Participation

Outreach Plan

Outreach Plan: The NC229 Committee members will develop educational outreach tools for disseminating information through established outreach and extension networks to producers, veterinarians, educators, and researchers. These will be coordinated and directed through the NPB. As specific knowledge is acquired on topics of PRRS and other swine viral diseases elimination, diagnosis and prevention, educational materials and operation manuals will be prepared and distributed via print and electronic media under the direction and coordination of the NPB and/or SHIC. Scientific communication will be managed by the NC-229 committee to assure full reporting of research findings in peer-reviewed scientific literature, abstracts and proceedings of relevant meetings and symposia, book chapters, and review articles. Timely communication will occur through the annual NC229 meeting and affiliated international/national symposia, particularly at the International/North American PRRS Symposia and CRWAD. The NC 229includes, since the renewal of 2014, international participants in China, Mexico, Spain and Russia. This expansion helps to increase opportunities for material interchanges, research planning a sharing of resources, and outreach.

Lists, descriptions, and sources of control standards, assay protocols, planned experiments, critical reagents, clones, and so forth will be permanently available for PRRS virus researchers on an NPB server. Further outreach will be achieved by continued participation of NC229 members in the academic swine conferences at the national (Allen Leman and John McKean Swine Disease Conference Symposium) and international (China Leman) levels


The program will be directed by the chair of NC-229 working with an executive committee comprising the chair, the past chair, and the secretary. Elections for chair and secretary are held every two years. The validity of NC-229 research objectives during the lifespan of this project will be gagged by input received from the National Pork Board ( their swine health committee or other ad hoc groups composed by NPB) and the American Association of Swine Veterinarians AASV at least once a year at the time of their annual meetings.

Literature Cited

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2: Popescu LN, Trible BR, Chen N, Rowland RRR. GP5 of porcine reproductive and respiratory syndrome virus (PRRSV) as a target for homologous and broadly neutralizing antibodies. Vet Microbiol. 2017 Sep;209:90-96. doi: 10.1016/j.vetmic.2017.04.016. Epub 2017 Apr 29. Review. PubMed PMID: 28528961. 

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4: Ke H, Yoo D. The viral innate immune antagonism and an alternative vaccine design for PRRS virus. Vet Microbiol. 2017 Sep;209:75-89. doi: 10.1016/j.vetmic.2017.03.014. Epub 2017 Mar 18. Review. PubMed PMID: 28341332. 

5: Harding JCS, Ladinig A, Novakovic P, Detmer SE, Wilkinson JM, Yang T, Lunney JK, Plastow GS. Novel insights into host responses and reproductive pathophysiology of porcine reproductive and respiratory syndrome caused by PRRSV-2. Vet Microbiol. 2017 Sep;209:114-123. doi: 10.1016/j.vetmic.2017.02.019. Epub 2017 Mar 2. Review. PubMed PMID: 28292546. 

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8: Vilalta C, Arruda AG, Tousignant SJP, Valdes-Donoso P, Muellner P, Muellner U,  Alkhamis MA, Morrison RB, Perez AM. A Review of Quantitative Tools Used to Assess the Epidemiology of Porcine Reproductive and Respiratory Syndrome in U.S. Swine Farms Using Dr. Morrison's Swine Health Monitoring Program Data. Front Vet Sci. 2017 Jun 27;4:94. doi: 10.3389/fvets.2017.00094. eCollection 2017. Review. PubMed PMID: 28702459; PubMed Central PMCID: PMC5484771. 

9: Rahe MC, Murtaugh MP. Mechanisms of Adaptive Immunity to Porcine Reproductive and Respiratory Syndrome Virus. Viruses. 2017 Jun 13;9(6). pii: E148. doi:10.3390/v9060148. Review. PubMed PMID: 28608816; PubMed Central PMCID: PMC5490824. 

10: Rahe MC, Murtaugh MP. Effector mechanisms of humoral immunity to porcine reproductive and respiratory syndrome virus. Vet Immunol Immunopathol. 2017 Apr;186:15-18. doi: 10.1016/j.vetimm.2017.02.002. Epub 2017 Feb 20. Review. PubMed PMID: 28413045; PubMed Central PMCID: PMC5398761. 

11: Niederwerder MC, Rowland RR. Is There a Risk for Introducing Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Through the Legal Importation of Pork? Food Environ Virol. 2017 Mar;9(1):1-13. doi: 10.1007/s12560-016-9259-z. Epub 2016 Sep 2. Review. PubMed PMID: 27590771. 

12: Alvarez J, Valdes-Donoso P, Tousignant S, Alkhamis M, Morrison R, Perez A. Novel analytic tools for the study of porcine reproductive and respiratory syndrome virus (PRRSv) in endemic settings: lessons learned in the U.S. Porcine Health Manag. 2016 Jan 21;2:3. doi: 10.1186/s40813-016-0019-0. eCollection 2016. Review. PubMed PMID: 28405429; PubMed Central PMCID: PMC5382381. 

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16: Brar MS, Shi M, Murtaugh MP, Leung FC. Evolutionary diversification of type 2 porcine reproductive and respiratory syndrome virus. J Gen Virol. 2015 Jul;96(Pt7):1570-80. doi: 10.1099/vir.0.000104. Epub 2015 Feb 24. Review. PubMed PMID: 25711962. 

17: Renukaradhya GJ, Meng XJ, Calvert JG, Roof M, Lager KM. Inactivated and subunit vaccines against porcine  reproductive and respiratory syndrome: Current status and future direction. Vaccine. 2015 Jun 17;33(27):3065-72. doi: 10.1016/j.vaccine.2015.04.102. Epub 2015 May 14. Review. PubMed PMID: 25980425. 

18: Zhang Q, Yoo D. PRRS virus receptors and their role for pathogenesis. Vet Microbiol. 2015 Jun 12;177(3-4):229-41. doi: 10.1016/j.vetmic.2015.04.002. Epub 2015 Apr 13. Review. PubMed PMID: 25912022. 

19: Kappes MA, Faaberg KS. PRRSV structure, replication and recombination: Origin of phenotype and genotype diversity. Virology. 2015 May;479-480:475-86. doi: 10.1016/j.virol.2015.02.012. Epub 2015 Mar 7. Review. PubMed PMID: 25759097. 

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21: Lu ZH, Archibald AL, Ait-Ali T. Beyond the whole genome consensus: unravelling of PRRSV phylogenomics using next generation sequencing technologies.Virus Res. 2014 Dec 19;194:167-74. doi: 10.1016/j.virusres.2014.10.004. Epub 2014 Oct 12. Review. PubMed PMID: 25312450; PubMed Central PMCID: PMC4275598. 

22: Han M, Yoo D. Modulation of innate immune signaling by nonstructural protein 1 (nsp1) in the family Arteriviridae. Virus Res. 2014 Dec 19;194:100-9. doi:10.1016/j.virusres.2014.09.007. Epub 2014 Sep 28. Review. PubMed PMID: 25262851. 

23: Han M, Yoo D. Engineering the PRRS virus genome: updates and perspectives. Vet Microbiol. 2014 Dec 5;174(3-4):279-295. doi: 10.1016/j.vetmic.2014.10.007. Epub 2014 Oct 23. Review. PubMed PMID: 25458419. 

24: USDA- NIFA request for proposals Sustainable Agricultural Systems( copy of 2018 RFP is shown,  call for FY 2019 is currently impending, Occurrence of future 2019 RFP has been confirmed by verbal communication of Dr Peter Johnson )

25. SHIC. 2018. Swine Health Information Center Progress Report 2017.

26. Dee SA, Bauermann FV, Niederwerder MC, Singrey A, Clement T, de Lima M, Long C, Patterson G, Sheahan MA, Stoian AMM, Petrovan V, Jones CK, De Jong J, Ji J, Spronk GD, Minion L, Christopher-Hennings J, Zimmerman JJ, Rowland RRR, Nelson E, Sundberg P, Diel DG. Survival of viral pathogens in animal feed ingredients under transboundary shipping models. PLoS One. 2018 Mar 20;13(3):e0194509. doi:10.1371/journal.pone.0194509. PubMed PMID: 29558524


Land Grant Participating States/Institutions


Non Land Grant Participating States/Institutions

Centro Nacional de Sanidad Agropecuaria CENSA, Iowa State University - College of Vet Med, Russia, Spain, University of Montreal, University of Wisconsin-Madison, USDA-ARS Beltsville Agricultural Resarch Center, USDA-ARS/Iowa, USDA-ARS/KS
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