Source: UNIV OF MARYLAND submitted to NRP
PREVENTION AND CONTROL OF AVIAN INFLUENZA IN THE U.S.
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
NRI COMPETITIVE GRANT
Reporting Frequency
Annual
Accession No.
0202495
Grant No.
2005-35605-15388
Cumulative Award Amt.
(N/A)
Proposal No.
2006-02748
Multistate No.
(N/A)
Project Start Date
Jan 15, 2005
Project End Date
Jan 14, 2010
Grant Year
2007
Program Code
[20.0]- Animal and Plant Biosecurity
Recipient Organization
UNIV OF MARYLAND
(N/A)
COLLEGE PARK,MD 20742
Performing Department
VETERINARY MEDICINE
Non Technical Summary
Waterfowl are the natural reservoir of influenza A viruses. Often, some of these viruses cross the species barrier infecting non-natural hosts such as land-based poultry, where they can increase their virulence and cause important economic losses due to mortality and trade restrictions. The molecular mechanisms that lead to the emergence of influenza viruses in land-based poultry are poorly defined, however their consequences are well known by all, e.g. farmers, the poultry industry, government officials, and scientists. Poultry production in the US amounts to approximately 18% of total world production and poultry has become the primary source of meat protein in the human diet in many countries. Effective detection and prevention of avian influenza are of the utmost importance to maintain the US leadership in world poultry product markets and such efforts will make a significant contribution towards national food security. These goals cannot be accomplished without solid scientific knowledge of the molecular and epizootiological bases for cross species transmission of influenza A viruses. To be useful this knowledge needs to be developed in the context of the actual production scenarios. We propose to develop reagents, technologies, and human resources aimed at detection and eradication of influenza from economically important poultry species. Furthermore, highly pathogenic avian influenza may pose a threat to public health. Thus, our efforts will also have a major impact on the prevention and control of zoonotic outbreaks of avian influenza.
Animal Health Component
40%
Research Effort Categories
Basic
40%
Applied
40%
Developmental
20%
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
3110820110110%
3113210110110%
3113220110110%
3113230110110%
3113599110110%
3114030110110%
3114030302010%
7224030110110%
7224030302010%
7234030302010%
Knowledge Area
311 - Animal Diseases; 722 - Zoonotic Diseases and Parasites Affecting Humans; 723 - Hazards to Human Health and Safety;

Subject Of Investigation
0820 - Wild birds; 3210 - Egg-type chicken, live animal; 3220 - Meat-type chicken, live animal; 3599 - Swine, general/other; 4030 - Viruses; 3230 - Turkey, live animal;

Field Of Science
1101 - Virology; 3020 - Education;
Goals / Objectives
2004-05523. Our long-term goal is to develop knowledge-based integrated approaches to detect, control and prevent the emergence of influenza viruses in avian species of economic importance. Aquatic birds are the primary reservoir of influenza A viruses. Often, some of these viruses cross the species barrier infecting non-natural hosts such as land-based poultry, without overt clinical signs. For reasons that are still poorly understood, influenza viruses circulating in land-based poultry can increase their virulence and cause important economic losses due to mortality and trade restrictions. The molecular mechanisms that lead to the emergence of influenza viruses in land-based poultry are poorly defined, however their consequences are well known by all, e.g. farmers, the poultry industry, government officials, and scientists. Poultry production in the US amounts to approximately 18% of total world production and poultry has become the most important source of meat protein in the human diet in many countries. Effective detection, control and prevention of avian influenza are of the utmost importance to maintain the US leadership in world poultry product markets and such efforts will make a significant contribution towards national food security. These goals cannot be accomplished without solid scientific knowledge of the molecular and epizootiological bases for the interspecies transmission of influenza A viruses including the factors contributing to high virulence in poultry. We propose to develop reagents, technologies, and human resources aimed at detection and eradication of influenza from economically important poultry species. Highly pathogenic avian influenza may pose a threat to public health, as evidenced by the transmission of avian influenza viruses from poultry to humans in Asia and the Netherlands. Thus, our efforts will also have a major impact on the prevention and control of zoonotic outbreaks of avian influenza. In this application, the efforts of several institutions across the country will concentrate on three major aims: Aim 1: 1) To determine the molecular basis for adaptation of influenza A viruses from wild aquatic birds and/or intermediate hosts to land-based poultry (chickens and turkeys). 2) To determine the molecular parameters for diagnosing avian influenza viruses in chickens and turkeys affected by co-infections by other respiratory and immunosuppressive viruses. Aim 2: 3) To determine the dynamics and evolution of influenza A viruses in live bird market systems (LBMs) in three areas of the United States. 4) To determine the dynamics and evolution of influenza A viruses in waterfowl of the four major flyways of the U.S to understand the contribution of these species to the emergence and perpetuation of avian influenza in land-based poultry. 5) To build effective education and biosecurity programs. 6) To deliver an educational program on in house euthanasia and composting methods for use in the case of catastrophic mortality or depopulation. Aim 3: 7) To develop critical diagnostic tests and, 8) vaccines for avian influenza control.
Project Methods
Aim 1: The critical first event in the development of HPAI is efficient replication of a LPAI. We will study the molecular basis that allows the transmission and perpetuation of AI from wild waterfowl to land-based poultry. We will use reverse genetics and classical virology to dissect the molecular events that take place for AI viruses to become endemic in land-based poultry. We propose to determine whether H5, H6, and H7 subtypes of influenza viruses present in wild aquatic birds can replicate in chickens and quail and whether quail enhance transmission to other bird species, particularly chickens and turkeys. We will determine the effect of other viral diseases such as NDV, IBDV, CIAV or HE viruses, on factors influencing the diagnosis of AI in poultry. Aim 2: We will investigate the risk factors associated with the emergence and perpetuation of AI in bird species in the LBM systems across the country. We will characterize AI circulating in wild waterfowl and their captive raised counterparts. Antigenic, molecular and in vivo characterizations will be performed to understand the movement of viruses across different bird species, the level of reassortment taking place and whether novel variants are generated. Surveillance activities will include collection of ground-truth data using GPS data collection systems. Educational programs and materials will be developed on avian influenza control including stand-up presentations, printed and on-line fact sheets, and CDs will be generated and delivered to targeted audiences including integrated and semi-integrated poultry meat and egg industry, allied industry representatives, independent poultry producers, poultry dealers and distributors, live bird market owners and workers, gamebird producers, poultry and waterfowl fanciers and 4-H club members. Aim 3: This objective addresses two key high priority needs: 1) Development of highly sensitive and rapid diagnostic tests for avian influenza during surveillance and outbreaks capable of discriminating between non-vaccinated and vaccinated birds as well as infected birds. 2) Development of alternative strategies for vaccination against avian influenza exploiting the latest molecular approaches available including reverse genetics and recombinant expression vectors. We propose to develop a rapid diagnostic test that is sensitive, inexpensive, and can be performed penside. The methods to be evaluated include an optical interferometric biosensor, serologic tests for different NA subtypes, a DNA microarray test, an Antibody-based Virus Concentrator, and microsphere -based multiplex immunoassays. Alternative vaccines strategies will include the evaluation of LPAI H5 and H7 strains as vaccine seeds for emergency vaccine stockpiles, the evaluation of antigenic drift in Mexican AI viruses using DNA vaccines, and the evaluation of six alternative strategies for vaccination against HPAI (and LPAI) using 1) a recombinant adenovirus vector, 2) a recombinant live lentogenic NDV vector, 3) a recombinant MDV vector, 4) a recombinant SFV suicide replicon, 5) a recombinant IBV vector, and 6) a whole RG AI vaccine.

Progress 01/15/05 to 01/14/10

Outputs
OUTPUTS: AICAP provided young investigators with opportunity to establish research on influenza. First, nationwide educational effort on mass euthanasia and composting methods for catastrophic diseases. First program on training and certification of gamebird producers and poultry handlers for prevention and control of avian influenza and Newcastle disease virus. First nationwide effort to explore the ecology of avian influenza in wild birds. Provided better understanding of the factors involved in transmission and perpetuation of avian influenza viruses in poultry and swine. Alternative vaccine vectors and diagnostic tools have been developed to prevent and detect avian influenza, respectively. PARTICIPANTS: Nothing significant to report during this reporting period. TARGET AUDIENCES: Commercial and small poultry producers, swine producers, avian ecologists, virologists, vaccine manufacturers and diagnostic companies PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
Programs on mass euthanasia and composting were successful in the US and requested and implemented in Brazil and Canada. Gamebird producer training sessions were implemented in more states than initially planned due to demand. Alternative vaccine vectors (NDV, adenovirus and live attenuated influenza) have attracted the attention of the poultry industry and potential commercialization in various stages of development depending on the approach. A diagnostic kit is commercially available (FluDetect).

Publications

  • Yassine HM, Khatri M, Zhang YJ, Lee CW, Byrum BA, O'Quin J, Smith KA, Saif YM. Characterization of triple reassortant H1N1 influenza A viruses from swine in Ohio. Vet Microbiol. 20;139(1-2):132-9. 2009.
  • Yassine YM, Lee CW, D.L. Suarez, Y.M. Saif. Genetic and Antigenic Relatedness of H3 Subtype Influenza A Viruses Isolated from Avian and Mammalian Species. Vaccine. 26(7):966-77. 2008.
  • Benson, E.R. To Cover or Not to Cover, That is the Question. Delmarva Farmer. February, 2010.
  • Benson, E.R. In search of a silver bullet Improving in house composting. Delmarva Farmer. August, 2009.
  • Benson, E.R. 2009. Should we vaccinate for Avian Influenza Delmarva Farmer. February, 2009.
  • R.L. Alphin, C. Ciaverelli, D.P. Hougentogler, K.J. Johnson, M.K. Rankin, and E.R. Benson. 2010. Post Outbreak Disinfection of Mobile Equipment. Avian Diseases. Accepted for publication.
  • R.L. Alphin, K.J. Johnson, B.S. Ladman, and E.R. Benson. 2009. Inactivation of Avian Influenza Virus Using Five Common Chemicals and One Detergent. Poultry Science. 88: 1181-1185.
  • Liu, Y., E. Mundt, A. Mundt, M. Sylte, D. Swayne, and M. Garcia. Development and evaluation of an avian influenza (AI) neuraminidase subtype 1 (N1) based serological ELISA for poultry using the differentiation of infected and vaccinated animals (DIVA) control strategy. Avian Dis. 2010, In Press.
  • Wang L, Yassine H, Saif YM, Lee CW. 2009. Developing live attenuated avian influenza virus in ovo vaccines forpoultry. Avian Diseases, no. In press.
  • L. Wang, DL Suarez, M Pantin-Jackwood, M Mibayashi, A Garcia-Sastre, YM Saif, Lee CW. Characterization of Influenza Virus Variants with Different Sizes of the Non-structural (NS) Genes and Their Potential as a Live Influenza Vaccine in Poultry. Vaccine. Vaccine. 26:3580-3586. 2008.
  • Lupiani B. Mozisek B., Mason P.W., Lamichhane C. and Reddy S.M. 2010. Simultaneous detection of avian influenza virus (AIV) NP and H5 antibodies in chicken sera using a fluorescence microsphere immunoassay (FMIA). Avian Diseases [Epub ahead of print] doi: 10.1637/9176-881809-DIGEST.1
  • Watson D.S., Reddy S.M., Brahmakshatriya V. and Lupiani B. 2009. A multiplexed immunoassay for detection of antibodies against avian influenzavirus. Journal of Immunological Methods. 340 (2): 123-131. Epub 2008 Nov 8
  • Dlugolenski, D., Hauck, R., Hogan, J.R., Michel, F. and E. Mundt (2009). Establishment of H5 specific monoclonal antibodies and the development of a competitive ELISA for detection of H5 antibodies in multiple species. Avian Diseases, in press.
  • Brahmakshatriya V., Lupiani B. and Reddy S.M. 2010. Characterization and evaluation of avian influenza NS1 mutant virus as a potential live and killed DIVA (differentiating between infected and vaccinated animals) vaccine for chickens. Vaccine (doi:10.1016/j.vaccine.2009.12.074). [Epub ahead of print]
  • Lupiani B. Mozisek B., Mason P.W., Lamichhane C. and Reddy S.M. 2010. Simultaneous detection of avian influenza virus (AIV) NP and H5 antibodies in chicken sera using a fluorescence microsphere immunoassay (FMIA). Avian Diseases [Epub ahead of print] doi: 10.1637/9176-881809-DIGEST.1
  • Brahmakshatriya V., Lupiani B., Brinlee J.L., Cepeda M., Pillai S.D., and Reddy S.M. 2009. Preliminary studies for inactivation of avian influenza virus (AIV) in poultry products using electron beam (E-beam) irradiation. Avian Pathology 38(3):245-250.
  • Watson D.S., Reddy S.M., Brahmakshatriya V. and Lupiani B. 2009. A multiplexed immunoassay for detection of antibodies against avian influenzavirus. Journal of Immunological Methods. 340 (2): 123-131. Epub 2008 Nov 8
  • Nayak B, Kumar S, Dinapoli JM, Paldurai A, Perez DR, Collins PL, Samal SK. Contributions of the Avian Influenza Virus HA, NA, and M2 Surface Proteins to the Induction of Neutralizing Antibodies and Protective Immunity. J Virol. 2010 Mar;84(5):2408-20. Epub 2009 Dec 23.
  • Yassine YM, M.Q. Al-Natour, Lee CW, and Y.M. Saif. Interspecies and Intraspecies Transmission of Triple Reassortant H3N2 Influenza A Viruses. Virology J. 28;4:129. 2007.
  • Nayak B, Rout SN, Kumar S, Khalil MS, Fouda MM, Ahmed LE, Earhart KC, Perez DR, Collins PL, Samal SK. Immunization of chickens with Newcastle disease virus expressing H5 hemagglutinin protects against highly pathogenic H5N1 avian influenza viruses. PLoS One. 2009 Aug 5;4(8):e6509.
  • Nayak B, Rout SN, Kumar S, Khalil MS, Fouda MM, Ahmed LE, Earhart KC, Perez DR, Collins PL, Samal SK. Immunization of chickens with Newcastle disease virus expressing H5 hemagglutinin protects against highly pathogenic H5N1 avian influenza viruses. PLoS One. 2009 Aug 5;4(8):e6509.
  • Ruixue Wang, Lindsey Soll, Vivien Dugan, Jonathan Runstadler, George Happ, Richard D. Slemons and Jeffery K. Taubenberger. Examining the hemagglutinin subtype diversity among wild duck-origin influenza A viruses using ethanol-fixed cloacal swabs and a novel RT-PCR method. Virology 375: 182-189, 2008.
  • Vivien G. Dugan, Rubin Chen, David J. Spiro, Naomi Sengamalay, Jennifer Zaborsky, Elodie Ghedin, Jacqueline Nolting, David E. Swayne, Jonathan A. Runstadler, George M. Happ, Dennis A. Senne, Ruixue Wang, Richard D. Slemons, Edward C. Holmes and Jeffery K. Taubenberger. The evolutionary genetics and emergence of avian influenza viruses in wild birds. PLoS Pathogens Vol 4, Issue 5, e1000076, pp 1-9, 2008.
  • Erica Spackman, Hon S. Ip, David L. Suarez, Richard Slemons, David Stallknecht. Analytical validation of a realtime reverse transcription polymerase chain reaction test for Pan-American lineage H7 subtype avian influenza viruses. J Vet Diag. Invest. 2008 Sep; 20(5):612-6.
  • David E. Swayne and R. D. Slemons. Using mean infectious dose of high- and low-pathogenicity avian influenza viruses originating from wild duck and poultry as one measure of infectivity and adaptation to poultry. Avian Dis. 2008 Sep; 52(3):455-60.
  • Carol Cardona, Richard Slemons, Daniel Perez. Overview of the USDA CSREES NRI Coordinated Agriculture Project for the Prevention and Control of Avian Influenza. Poultry Sci. 88: 837-841, 2009.
  • Toro, H., D. C. Tang, D. L. Suarez, M. J. Sylte, J. Pfeiffer, K. R. van Kampen (2007). Protective avian influenza in ovo vaccination with non-replicating human adenovirus vector. Vaccine 25: 2886-2891.
  • Collisson, EW, Singh, S & Omran, T. 2007. Developments in avian influenza virus vaccines. Invited review. Journal of Poultry Science, 44:238-257.
  • Toro, H., D. C. Tang, D. Suarez, J. Zhang, Z. Shi (2008). Protection of chickens against avian influenza with non-replicating adenovirus-vectored vaccine. Vaccine 26: 2640-2646.
  • Van Ginkel, F. W., D. C. Tang, S. L. Gulley, and H. Toro. Induction of mucosal immunity in the avian Harderian gland with a replication deficient Ad-5 vector expressing avian influenza H5 hemagglutinin. Developmental & Comparative Immunology 33:28-34. 2009.
  • Toro, H. & D. C. Tang (2009). Protection of Chickens against Avian Influenza with Non-Replicating Adenovirus-Vectored Vaccine. Poultry Science 88:867-871.
  • Collisson, EW, Drechsler, Y & Singh, S. (2008). Evolving vaccine choices for the continuously evolving avian influenza virus. Invited review, CAP Reviews: Perspectives in Agriculture, Veterinary Medicine, Nutrition and Natural Resources, 3 (088) 17 pp.
  • Tang, D. C., J. Zhang, H. Toro, Z. Shi, & K. R. van Kampen (2009). Adenovirus as a carrier for influenza virus-free avian influenza vaccines. Expert Reviews of Vaccines 8 (4): 469-481
  • Toro, H., F. van Ginkel, D.C. Tang, B. Schemera, S. Rodning, J. Newton (2009) Avian Influenza Vaccination in Chickens and Pigs with RCA-free Human Recombinant Adenovirus 5. Avian Diseases Avian Influenza Supplement (in press).
  • Shailbala Singh, Haroldo Toro, De-Chu Tang, Worthie E. Briles, and Ellen W. Collisson. Non-replicating adenovirus vectors expressing avian influenza virus hemagglutinin and nucleocapsid proteins induce chicken specific memory CD8+ t lymphocyte responses. European Journal of Immunology (Submitted for publication January 2010).
  • Singh, S, Briles, WE, Lupiani, B and Collisson, EW. 2010. Avian influenza viral nucleocapsid and hemagglutinin proteins induce chicken CD8+ memory T lymphocytes. Virology, in press.
  • Sun K, Ye J, Perez DR, Metzger DW. Seasonal FluMist Vaccination Induces Cross-Reactive T Cell Immunity against H1N1 (2009) Influenza and Secondary Bacterial Infections. J Immunol. 2010 Dec 15. [Epub ahead of print]
  • Kimble B, Ramirez Nieto G, Perez DR . Characterization of influenza virus sialic acid receptors in minor poultry species.Virol J. 2010 Dec 9;7(1):365. [Epub ahead of print] PMID: 21143937 [PubMed - as supplied by publisher]
  • Ye J, Sorrell EM, Cai Y, Shao H, Xu K, Pena L, Hickman D, Song H, Angel M, Medina RA, Manicassamy B, Garcia-Sastre A, Perez DR. Variations in the hemagglutinin of the 2009 H1N1 pandemic virus: potential for strains with altered virulence phenotype PLoS Pathog. 2010 Oct 14;6(10):e1001145. PMID: 20976194 [PubMed - in process] Free PMC Article Free text
  • Pena L, Vincent AL, Ye J, Ciacci-Zanella JR, Angel M, Lorusso A, Gauger PC, Janke BH, Loving CL, Perez DR. Modifications in the polymerase genes of a swine-like triple reassortant influenza virus to generate live attenuated vaccines against 2009 pandemic H1N1 viruses. J Virol. 2010 Oct 20. [Epub ahead of print] PMID: 20962084 [PubMed - as supplied by publisher]
  • Ramirez-Nieto G, Shivaprasad HL, Kim CH, Lillehoj HS, Song H, Osorio IG, Perez DR. Adaptation of a mallard H5N2 low pathogenicity influenza virus in chickens with prior history of infection with infectious bursal disease virus. Avian Dis. 2010 Mar;54(1 Suppl):513-21. PMID: 20521687 [PubMed - indexed for MEDLINE]
  • Chutinimitkul S, Herfst S, Steel J, Lowen AC, Ye J, van Riel D, Schrauwen EJ, Bestebroer TM, Koel B, Burke DF, Sutherland-Cash KH, Whittleston CS, Russell CA, Wales DJ, Smith DJ, Jonges M, Meijer A, Koopmans M, Rimmelzwaan GF, Kuiken T, Osterhaus AD, Garcia-Sastre A, Perez DR, Fouchier RA. Virulence-associated substitution D222G in the hemagglutinin of 2009 pandemic influenza A(H1N1) virus affects receptor binding. J Virol. 2010 Nov;84(22):11802-13. Epub 2010 Sep 15. PMID: 20844044 [PubMed - in process]
  • Sorrell EM, Song H, Pena L, Perez DR. A 27-amino-acid deletion in the neuraminidase stalk supports replication of an avian H2N2 influenza A virus in the respiratory tract of chickens. J Virol. 2010 Nov;84(22):11831-40. Epub 2010 Sep 8. PMID: 20826691 [PubMed - in process]
  • Ye J, Shao H, Hickman D, Angel M, Xu K, Cai Y, Song H, Fouchier RA, Qin A, Perez DR. Intranasal delivery of an IgA monoclonal antibody effective against sublethal H5N1 influenza virus infection in mice. Clin Vaccine Immunol. 2010 Sep;17(9):1363-70. Epub 2010 Jul 28. PMID: 20668143 [PubMed - in process] Free PMC Article Free text
  • Hale BG, Steel J, Medina RA, Manicassamy B, Ye J, Hickman D, Hai R, Schmolke M, Lowen AC, Perez DR, Garcia-Sastre A. Inefficient control of host gene expression by the 2009 pandemic H1N1 influenza A virus NS1 protein. J Virol. 2010 Jul;84(14):6909-22. Epub 2010 May 5. PMID: 20444891 [PubMed - indexed for MEDLINE]
  • Hale BG, Steel J, Manicassamy B, Medina RA, Ye J, Hickman D, Lowen AC, Perez DR, Garcia-Sastre A. Mutations in the NS1 C-terminal tail do not enhance replication or virulence of the 2009 pandemic H1N1 influenza A virus. J Gen Virol. 2010 Jul;91(Pt 7):1737-42. Epub 2010 Mar 17. PMID: 20237225 [PubMed - indexed for MEDLINE]
  • Solorzano A, Ye J, Perez DR. Alternative live-attenuated influenza vaccines based on modifications in the polymerase genes protect against epidemic and pandemic flu. J Virol. 2010 May;84(9):4587-96. Epub 2010 Feb 24. PMID: 20181702 [PubMed - indexed for MEDLINE] Free PMC Article Free text
  • Herfst S, Chutinimitkul S, Ye J, de Wit E, Munster VJ, Schrauwen EJ, Bestebroer TM, Jonges M, Meijer A, Koopmans M, Rimmelzwaan GF, Osterhaus AD, Perez DR, Fouchier RA. Introduction of virulence markers in PB2 of pandemic swine-origin influenza virus does not result in enhanced virulence or transmission. J Virol. 2010 Apr;84(8):3752-8. Epub 2010 Feb 3. PMID: 20130063 [PubMed - indexed for MEDLINE] Free PMC Article Free text
  • Perez DR, Sorrell E, Angel M, Ye J, Hickman D, Pena L, Ramirez-Nieto G, Kimble B, Araya Y. Fitness of pandemic H1N1 and seasonal influenza A viruses during co-infection: evidence of competitive advantage of pandemic H1N1 influenza versus seasonal influenza. PLoS Curr. 2009 Aug 24;1:RRN1011. PMID: 20029606 [PubMed] Free PMC Article Free text
  • Song H, Wan H, Araya Y, Perez DR. Partial direct contact transmission in ferrets of a mallard H7N3 influenza virus with typical avian-like receptor specificity. Virol J. 2009 Aug 14;6:126. PMID: 19682381 [PubMed - indexed for MEDLINE] Free PMC Article Free text
  • Sorrell EM, Wan H, Araya Y, Song H, Perez DR. Minimal molecular constraints for respiratory droplet transmission of an avian-human H9N2 influenza A virus. Proc Natl Acad Sci U S A. 2009 May 5;106(18):7565-70. Epub 2009 Apr 20. PMID: 19380727 [PubMed - indexed for MEDLINE] Free PMC Article Free text
  • Xing Z, Cardona CJ, Adams S, Yang Z, Li J, Perez D, Woolcock PR. Differential regulation of antiviral and proinflammatory cytokines and suppression of Fas-mediated apoptosis by NS1 of H9N2 avian influenza virus in chicken macrophages. J Gen Virol. 2009 May;90(Pt 5):1109-18. Epub 2009 Mar 4. PMID: 19264628 [PubMed - indexed for MEDLINE] Free Article
  • Steel J, Lowen AC, Pena L, Angel M, Solorzano A, Albrecht R, Perez DR, Garcia-Sastre A, Palese P. Live attenuated influenza viruses containing NS1 truncations as vaccine candidates against H5N1 highly pathogenic avian influenza. J Virol. 2009 Feb;83(4):1742-53. Epub 2008 Dec 10. PMID: 19073731
  • Hickman D, Hossain MJ, Song H, Araya Y, Solorzano A, Perez DR. An avian live attenuated master backbone for potential use in epidemic and pandemic influenza vaccines. J Gen Virol. 2008 Nov;89(Pt 11):2682-90. PMID: 18931063 [PubMed - indexed for MEDLINE] Free PMC Article Free text
  • Hossain MJ, Hickman D, Perez DR. Evidence of expanded host range and mammalian-associated genetic changes in a duck H9N2 influenza virus following adaptation in quail and chickens. PLoS One. 2008 Sep 9;3(9):e3170. PMID: 18779858 [PubMed - indexed for MEDLINE]Free PMC Article Free text
  • Wan H, Sorrell EM, Song H, Hossain MJ, Ramirez-Nieto G, Monne I, Stevens J, Cattoli G, Capua I, Chen LM, Donis RO, Busch J, Paulson JC, Brockwell C, Webby R, Blanco J, Al-Natour MQ, Perez DR. Replication and transmission of H9N2 influenza viruses in ferrets: evaluation of pandemic potential. PLoS One. 2008 Aug 13;3(8):e2923. PMID: 18698430 [PubMed - indexed for MEDLINE] Free PMC Article Free text
  • Pereda AJ, Uhart M, Perez AA, Zaccagnini ME, La Sala L, Decarre J, Goijman A, Solari L, Suarez R, Craig MI, Vagnozzi A, Rimondi A, Konig G, Terrera MV, Kaloghlian A, Song H, Sorrell EM, Perez DR. Avian influenza virus isolated in wild waterfowl in Argentina: evidence of a potentially unique phylogenetic lineage in South America. Virology. 2008 Sep 1;378(2):363-70. Epub 2008 Jul 15. PMID: 18632129 [PubMed - indexed for MEDLINE] Free PMC Article Free text
  • Jackson D, Hossain MJ, Hickman D, Perez DR, Lamb RA. A new influenza virus virulence determinant: the NS1 protein four C-terminal residues modulate pathogenicity. Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4381-6. Epub 2008 Mar 11. PMID: 18334632 [PubMed - indexed for MEDLINE] Free PMC Article Free text
  • Rao S, Kong WP, Wei CJ, Yang ZY, Nason M, Styles D, DeTolla LJ, Panda A, Sorrell EM, Song H, Wan H, Ramirez-Nieto GC, Perez D, Nabel GJ. Multivalent HA DNA vaccination protects against highly pathogenic H5N1 avian influenza infection in chickens and mice. PLoS One. 2008;3(6):e2432. Epub 2008 Jun 18.
  • Solorzano A, Song H, Hickman D, Perez DR. Pandemic influenza: preventing the emergence of novel strains and countermeasures to ameliorate its effects. Infect Disord Drug Targets. 2007 Dec;7(4):304-17. Review. PMID: 18220962 [PubMed - indexed for MEDLINE]
  • Genesis of pandemic influenza. Sorrell EM, Ramirez-Nieto GC, Gomez-Osorio IG, Perez DR. Cytogenet Genome Res. 2007;117(1-4):394-402. Review. PMID: 17675883 [PubMed - indexed for MEDLINE]
  • Song H, Nieto GR, Perez DR. A new generation of modified live-attenuated avian influenza viruses using a two-strategy combination as potential vaccine candidates. J Virol. 2007 Sep;81(17):9238-48. Epub 2007 Jun 27. PMID: 17596317 [PubMed - indexed for MEDLINE] Free PMC Article Free text
  • Sorrell EM, Perez DR. Adaptation of influenza A/Mallard/Potsdam/178-4/83 H2N2 virus in Japanese quail leads to infection and transmission in chickens. Avian Dis. 2007 Mar;51(1 Suppl):264-8. PMID: 17494563 [PubMed - indexed for MEDLINE]
  • Wan H, Perez DR.Amino acid 226 in the hemagglutinin of H9N2 influenza viruses determines cell tropism and replication in human airway epithelial cells. J Virol. 2007 May;81(10):5181-91. Epub 2007 Mar 7. PMID: 17344280 [PubMed - indexed for MEDLINE] Free PMC Article Free text
  • Lavoie ET, Sorrell EM, Perez DR, Ottinger MA. Immunosenescence and age-related susceptibility to influenza virus in Japanese quail. Dev Comp Immunol. 2007;31(4):407-14. Epub 2006 Sep 20. PMID: 17045650 [PubMed - indexed for MEDLINE]


Progress 01/15/06 to 01/14/07

Outputs
The long-term goal of the AICAP program is to serve as a significant point of reference for the poultry industry and the general public in matters related to the biology, risks associated with and the methods used to prevent and control avian influenza (AI). Due to character limitations for submission of the report we are including the final report on Education efforts, which were devised as two-year projects. Drs. Eric Benson, Robert Alphin, and George Malone at the University of Delaware, in close collaboration with Dr. Nathaniel Tablante at the University of Maryland, have continued to advance and expand their programs to test the environmental stability of avian influenza and practical methods for viral inactivation on poultry premises. A half-day comprehensive classroom training program was developed in the Spring of 2005. Content of the training material included: current status of avian influenza worldwide, human health guidelines for responders to an avian influenza outbreak; requirements, options and procedures for mass depopulation; disposal options, procedures and cost with comprehensive details for in-house windrow composting. Demand for this train- the-trainer program far exceeded the initial projections: a total of 32 sessions were held in 26 different states. Additionally, the Canadian poultry industry requested and supported 5 sessions in four different provinces. A condensed version of this material was also offered at two locations in Brazil (again, supported by the Brazilian government). In the United States, an estimated 1,800 people total attended the 32 sessions. Participants included 45% poultry industry personnel (poultry company health, production, safety and environmental managers), 40% agencies (Department of Agriculture, USDA, emergency management), 10% university professionals and cooperative extension staff and 5% private industry (waste and emergency management firms). In addition, Dr Eva Wallner-Pendleton at Penn State traveled extensively to host educational trainings, reaching over 1,250 participants in Kansas, South Dakota, Minnesota, Washington, Alabama, South Carolina, Connecticut, Pennsylvania, Tennessee, Texas, Florida and California. Surveys were collected from over 60 live bird market (LBM) producers, the results of which are being tabulated. Sampling of live bird markets (LBM) and wild migratory birds is a critical component of the AICAP project, as the project structure facilitates rapid information sharing between researchers and institutions in different states. In order to better understand the procedures of the live bird market producers, Dr. Cardona's team at University of California, Davis delivered a questionnaire to 29 out of 31 custom slaughter markets south of the Tehachapi mountains in California. The questionnaire was delivered in person to each market manager who answered questions on market practices and patterns, depopulations, employee movements and market biosecurity. This survey data is available to researchers in other states, which creates a valuable database of information for both researchers and government institutions.

Impacts
The second year of the AICAP program has demonstrated the value of the coordinated agricultural projects (CAP) created by CSREES/USDA. The addition of several new researchers, the seamless addition of expanded and collaborative surveillance efforts, and the continued cross-communication occurring between AICAP research institutions are markers of success for the second year of the AICAP program. A redesigned website (www.aicap.umd.edu) was launched in 2006, with a secure login area for researchers to share information and updates, along with public access to researcher publications and education materials. Problems that had previously delayed the release of funds were surmounted, with funds released to all subcontractors as of the beginning of February. This represents a significant advancement in the unified efforts of all researchers; projects currently underway will continue with no funding interruption and new researchers have a full year to demonstrate scientific progress. Of invaluable worth to the program is the input of all project participants, our constant interaction with members of the scientific advisory board, executive committee and stakeholders. We want to create the opportunity for education of the general public on different aspects of AI and be a constant source of information for the large and small poultry producer. Thus, the overall goals of the AICAP project remain the same.

Publications

  • *Gross, D.K., P.S. Morley, K.W. Hinchcliff, J.K. Reichle, and R.D. Slemons. Pulmonary ultrasonographic abnormalities associated with naturally occurring equine influenza virus infection in standardbred racehorses. J. Vet. Intern. Med. 18:718-727, 2004. (* = graduate advisee)
  • Spackman, E., Stallknecht, D.E., Slemons, R.D., Winker, K., Suarez, D.L., Scott, M.A., Swayne, D.E. Phylogenetic Analyses of Type a Influenza Genes in Natural Reservoir Species in North America Reveals Genetic Variation. Virus Research, 114:89-100, 2005.
  • Lee CW, Lee YJ, Senne DA, Suarez DL. Pathogenic potential of North American H7N2 avian influenza virus: a mutagenesis study using reverse genetics. Virology. 2006 Sep 30;353(2):388-95. Epub 2006 Jul 10.
  • Toro H, Tang DC, Suarez DL, Sylte MJ, Pfeiffer J, Van Kampen KR. Protective avian influenza in ovo vaccination with non-replicating human adenovirus vector. Vaccine. 2006 Sep 25; [Epub ahead of print]
  • M.D. Dawson, E.R. Benson, R. Alphin, G.W. Malone, I. Estevez, and G.L. Van Wicklen. 2006. Fire Fighting Foams as an Alternative Method of Mass Euthanasia for Poultry Flock Disease Control. Poultry Science. In Review.
  • M.D. Dawson, P.L. Reyes, E.R. Benson, R.L. Alphin, G.W. Malone, G.L. Van Wicklen, and I. Estevez. 2006. Evaluation of Foam Based Humane Mass Euthanasia Methodology for Floor-Reared Meat-Type Poultry Operations. Applied Engineering in Agriculture. 22(5): 787-794.
  • Cardona CJ. Low-pathogenicity avian influenza outbreaks in commercial poultry in California. The Threat of Pandemic Influenza: Are We Ready? Workshop Summary, Proceedings for the Symposium on Pandemic Influenza Preparedness, Institute of Medicine, Washington D.C., 2004, 243-, 2004.
  • Woolcock PR, Cardona CJ. Commercial immunoassay kits for the detection of influenza virus type A: evaluation of their use with poultry. Avian Dis, 2005, 49(4): 477-81.
  • Cardona CJ, Charlton BR, Woolcock PR. Persistence of immunity in commercial egg-laying hens following vaccination with a killed H6N2 avian influenza vaccine. Avian Dis, 2006, 50(3): 374-9
  • Lupiani, B. and Reddy, S. 2005. Improved Diagnostic Tests for Avian Influenza Surveillance. Proceedings of the 1st Annual Food Protection and Defense Research Conference Papers November 2-4, Atlanta, GA.
  • Ge, Q., Pastey, M.K., Kobasa, D., Puthavathana, P., Lupfer, C., Bestwick, R. K., Iversen, P.I., Chen, J and Stein, D.A (2006). Inhibition of Multiple Subtypes of Influenza A Virus in Cell Cultures with Morpholino Oligomers. Antimicrobial Agents and Chemotherapy, 50: 3724-3733.
  • Lipatov AS, Andreansky S, Webby RJ, Hulse DJ, Rehg JE, Krauss S, Perez DR, Doherty PC, Webster RG, Sangster MY. Pathogenesis of Hong Kong H5N1 influenza virus NS gene reassortants in mice: the role of cytokines and B- and T-cell responses. J Gen Virol. 2005 Apr;86(Pt 4):1121-1130.
  • Y. Tang, C. W. Lee, Y. Zhang, D. A. Senne , R. Dearth, B. Byrum, D. R. Perez, D. L. Suarez, and Y. M. Saif. Isolation and Characterization of H3N2 Influenza A Virus from Turkeys. Avian Dis. 2005 Jun;49(2):207-213
  • Wan, H., and D. R. Perez. 2005. Quail carry sialic acid receptors compatible with binding of avian and human influenza viruses. Virology. 2006 Mar 15;346(2):278-86. Epub 2005 Dec 2.
  • Perez DR, Sorrell EM, Donis RO. Avian influenza: an omnipresent pandemic threat. Pediatr Infect Dis J. 2005 Nov;24(11 Suppl):S208-16, discussion S215. Review.
  • Huber VC, McKeon RM, Brackin MN, Miller LA, Keating R, Brown SA, Makarova N, Perez DR, Macdonald GH, McCullers JA. Distinct contributions of vaccine-induced immunoglobulin G1 (IgG1) and IgG2a antibodies to protective immunity against influenza. Clin Vaccine Immunol. 2006 Sep;13(9):981-90.
  • Lavoie ET, Sorrell EM, Perez DR, Ann Ottinger M. Immunosenescence and age-related susceptibility to influenza virus in Japanese quail. Dev Comp Immunol. 2006 Sep 20; [Epub ahead of print]
  • Sorrell, EM, Perez, DR. Adaptation of Influenza A/Mallard/Potsdam/178-4/83, H2N2 Virus in Japanese Quail leads to Infection and transmission in Chickens. Avian Dis. 2006 (accepted, in press)


Progress 01/15/07 to 01/14/07

Outputs
The AICAP has continued with focusing on several major aspects of AI research and education. The group has made progress in the areas of interspecies transmission and pathogenesis, ecology, development of education programs for the game bird industry, programs on mass euthanasia for catastrophic diseases and composting. The AICAP has also succeeded in developing alternative diagnostic tools and vaccine strategies to prevent and control AI

Impacts
The outcomes are mainly highlighted by publications and also from the implementation of several educational training session, the demand for the latter has increased over the part year. This project is very large and comprehensive, the space and characters limit provided does not allow for a thorough description of the outcomes and impacts for each area.

Publications

  • Runstadler JA, Happ GM, Slemons RD, Sheng ZM, Gundlach N, Petrula M, Senne D, Nolting J, Evers DL, Modrell A, Huson H, Hills S, Rothe T, Marr T, Taubenberger JK. (2007) Using RRT-PCR analysis and virus isolation to determine the prevalence of avian influenza virus infections in ducks at Minto Flats State Game Refuge, Alaska, during August 2005. Arch Virol. Jun 1; [Epub ahead of print]
  • Song H, Nieto GR, Perez DR. (2007 ) A new generation of modified live-attenuated avian influenza viruses using a two-strategy combination as potential vaccine candidates. J Virol. Jun 27; [Epub ahead of print].
  • Note: publications include participation of AICAP members, not necessarily that the work of the publication was funded by AICAP. Tang Y, Lee CW, Zhang Y, Senne DA, Dearth R, Byrum B, Perez DR, Suarez DL, Saif YM. (2005) Isolation and characterization of H3N2 influenza A virus from turkeys. Avian Dis. Jun;49(2):207-13. Wan H, Perez, DR. (2006) Quail carry receptors compatible with binding of human and avian influenza viruses. Virology, Mar 15;346(2):278-86
  • Sorrell, EM, Perez, DR. (2007) Adaptation of Influenza A/Mallard/Potsdam/178-4/83, H2N2 Virus in Japanese Quail Leads to Infection and Transmission in Chickens. Avian Dis. (in press)
  • Wan H, Perez DR. (2007) Amino acid 226 in the hemagglutinin of H9N2 influenza viruses determines cell tropism and replication in human airway epithelial cells. J Virol. Mar 7


Progress 01/15/05 to 01/14/07

Outputs
OUTPUTS: The long-term goal of the program entitled "Prevention and Control of Avian Influenza in the US" (AICAP) is to serve as a significant point of reference for the poultry industry and the general public in matters related to the biology, risks associated with and the methods used to prevent and control avian influenza (AI). Our major goal was to develop a collective network research structure that establishes the basis for a better understanding of avian influenza; in terms of the mechanisms that lead to the emergence of avian influenza in poultry, and, more importantly, how to prevent it. Over the course of the past two years, we have established such a structure. Through our research network, several of our groups have engaged in collaborative projects both within the AICAP and outside the network. We have developed a website for our project (http://www.aicap.umd.edu/ ) which lists current publications, researchers and educational materials from the twenty-two subcontracting institutions under the AICAP research structure. The network of researchers involved in the AICAP project continues to expand, with three new institutions added in the second year, without an increase in funding requested. PARTICIPANTS: Nothing significant to report during this reporting period. TARGET AUDIENCES: Commercial poultry producers, gamebird producers, backyard flock owners, vaccine and diagnostic companies, venture capitalists. PROJECT MODIFICATIONS: The project is being continued through AICAP 2 maintaining the overall goal of integrating basic research, practical methods of AI prevention and control, educational programs and development of alternative vaccine and diagnostic methods

Impacts
The first 3-year phase of our program resulted in significant achievements: * assembled the first continent-wide network to study the ecological and biological characteristics of avian influenza viruses isolated from wild birds; * integrated research and education into a unique program available to a range of poultry producers; * shown that quail can change and expand the host range of avian influenza viruses, and found that quail respiratory and intestinal tracts have human-like sialic acid receptors that could partially explain the emergence of avian influenza strains with the capacity to infect humans; * developed a comprehensive program that has been delivered in 33 states and in Canada and Brazil to train producers and veterinarians on the depopulation and composting of flocks with avian influenza; * developed a testing component for rapid diagnosis of avian influenza in birds; and * developed promising vaccines for mass immunization of birds.

Publications

  • Perez, DR (2005). Prevention and Control of Avian Influenza in the US. List of publications, educational materials, presentations and newsletters can be found in www.aicap.umd.edu


Progress 01/15/05 to 01/14/06

Outputs
The program Prevention and Control of Avian Influenza in the US (AICAP) has developed a collective network research structure to establish the basis for a better understanding of AI; both the mechanisms that lead to the emergence of AI, and, more importantly, the prevention of AI in poultry. During the first year of funding we have established such a structure: through our research network, several of our groups have engaged in collaborative projects both within AICAP and outside the network. We have developed a website for our project (www.agnr.umd.edu/aicap), which serves as a portal for distribution of educational materials and details the projects that received funding during 2005. Given the size and broad scope of the project, coordination of the different project areas has been a major challenge. However, we are excited to note that major progress has been made in all areas of research, although due to space constraints we highlight only those with major advances during 2005. Drs. Benson, Alphin, and Malone (U. Delaware), and Tablante (U. Maryland): Environmental stability of AI and practical methods for mass euthanasia and viral inactivation on poultry premises. Training sessions were organized and held at: Millsboro, DE; Moorefield, WV; Harrisonburg, VA; Statesville, NC; Lumberton, NC; Mt. Olive, NC; Lancaster, PA; Columbia, SC; APHIS/Riverdale, MD; Athens, GA; Montgomery, AL; Nashville, TN; Princeton, KY; Fayetteville, AR; Hope, AR; and Ruston, LA. Drs. Wallner-Pendleton, Dunn, and Lu (PSU): AI workshop training sessions for game bird producers. This project has been reaching out to game bird breeders with information on avian influenza, biosecurity steps to prevent infection and training in necropsy, serological sample taking and steps to becoming NPIP AI Clean according to subpart E. Game bird health workshops were held in South Carolina, Texas, California, Kansas and Minnesota with largely excellent attendance. Several presentations were added to the AI CAP website under education and were favorably reviewed. Dr. Gottfried, (GTRI): development of a cost-effective biosensor for the direct measurement of antibody-antigen complexes. AI subtype H7 was detected in both a direct antigen capture as well as a sandwich assay using surface attached antibodies, with sensitivity 2-3 orders of magnitude better than the Binax immunochromatographic assay. Dr. Keeler (U. Delaware) subtyping AI by cDNA microarray met a major objective, which is the ability of one labeling reaction and one slide to identify both HA and NA subtypes. Drs. Vakharia and Perez (U. Maryland), baculovirus expressed NP AI antigen produced and licensed to Synbiotics, Inc., which has manufactured two AI diagnostic kits that have been approved for commercialization in domestic and international markets. Drs. Wan and Perez have recently provided evidence on the potential role of quail as an intermediate host in which AI viruses can acquire features typical of human viruses. Quail (and chickens) show abundant human-like receptors in the respiratory and intestinal tract, which explains in part how human flu-like viruses could emerge.

Impacts
The input of all project participants, our interaction with members of the scientific advisory board (SAB), executive committee and stakeholders is highly valuable for the project. The interaction with members of APHIS (Dr. Tracy Duvernoy and others) has resulted in important exchange of ideas to improve the AICAP. These interactions will continue to make a major impact in the overall strategy to prevent and control AI in the US. In 2006, a completely re-designed AICAP website will be more user-friendly for exchange of information among project participants and the poultry industry. We will create the opportunity for education of the general public and poultry producers on different aspects of AI. As the project starts to take the form of a cohesive unit, we will be making major contributions with our surveillance efforts, particularly through the work of the two umbrella projects on wild bird and live bird market surveillance (Drs. Slemons and Cardona). For 2006, 21 applications, four of them new, were submitted for consideration for funding. For 2006, the overall aims of the project will remain the same: 1) To establish the molecular basis for avian influenza interspecies transmission and pathogenesis 2) To continue expanding our wild bird surveillance capacity and characterize the population of AI viruses in wild birds in North America. 3) To continue our different education programs and analysis of risk factors in the emergence of AI 4) To continue exploring and validating alternative diagnostic tools and vaccines strategies

Publications

  • Lipatov AS, Andreansky S, Webby RJ, Hulse DJ, Rehg JE, Krauss S, Perez DR, Doherty PC, Webster RG, Sangster MY. Pathogenesis of Hong Kong H5N1 influenza virus NS gene reassortants in mice: the role of cytokines and B- and T-cell responses. J Gen Virol. 2005 Apr;86(Pt 4):1121-30.
  • Y. Tang, C. W. Lee, Y. Zhang, D. A. Senne , R. Dearth, B. Byrum, D. R. Perez, D. L. Suarez, and Y. M. Saif. Isolation and Characterization of H3N2 Influenza A Virus from Turkeys. Avian Dis. 2005 Jun;49(2):207-13
  • (Only those in which the Program Director has been involved are listed, more will be added at a later time or in our next report). 2005
  • Perez DR, Sorrell EM, Donis RO. Avian influenza: an omnipresent pandemic threat. Pediatr Infect Dis J. 2005 Nov;24(11 Suppl):S208-16, discussion S215.
  • Wan H, Perez DR. Quail carry sialic acid receptors compatible with binding avian and human influenza viruses. Virology 2005 Dec 1