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Oral Fluids as a Live-Animal Sample Source for Evaluating Cross-Reactivity and Cross-Protection following Intranasal Influenza A Virus Vaccination in Pigs.

Abstract

In North American swine, there are numerous antigenically distinct H1 influenza A virus (IAV) variants currently circulating, making vaccine development difficult due to the inability to formulate a vaccine that provides broad cross-protection. Experimentally, live-attenuated influenza virus (LAIV) vaccines demonstrate increased cross-protection compared to inactivated vaccines. However, there is no standardized assay to predict cross-protection following LAIV vaccination. Hemagglutination-inhibiting (HI) antibody in serum is the gold standard correlate of protection following IAV vaccination. LAIV vaccination does not induce a robust serum HI antibody titer; however, a local mucosal antibody response is elicited. Thus, a live-animal sample source that could be used to evaluate LAIV immunogenicity and cross-protection is needed. Here, we evaluated the use of oral fluids (OF) and nasal wash (NW) collected after IAV inoculation as a live-animal sample source in an enzyme-linked immunosorbent assay (ELISA) to predict cross-protection in comparison to traditional serology. Both live-virus exposure and LAIV vaccination provided heterologous protection, though protection was greatest against more closely phylogenetically related viruses. IAV-specific IgA was detected in NW and OF samples and was cross-reactive to representative IAV from each H1 cluster. Endpoint titers of cross-reactive IgA in OF from pigs exposed to live virus was associated with heterologous protection. While LAIV vaccination provided significant protection, LAIV immunogenicity was reduced compared to live-virus exposure. These data suggest that OF from pigs inoculated with wild-type IAV, with surface genes that match the LAIV seed strain, could be used in an ELISA to assess cross-protection and the antigenic relatedness of circulating and emerging IAV in swine.

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  • Authors+Show Affiliations

    ,

    Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, Agricultural Research Services, U.S. Department of Agriculture, Ames, Iowa, USA.

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    Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, Agricultural Research Services, U.S. Department of Agriculture, Ames, Iowa, USA.

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    Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, Agricultural Research Services, U.S. Department of Agriculture, Ames, Iowa, USA.

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    Department of Veterinary Diagnostic and Production Animal Medicine, Iowa State University, Ames, Iowa, USA.

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    Department of Veterinary Medicine, University of Maryland, College Park, College Park, Maryland, USA.

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    Department of Veterinary Medicine, University of Maryland, College Park, College Park, Maryland, USA.

    ,

    Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, Agricultural Research Services, U.S. Department of Agriculture, Ames, Iowa, USA.

    ,

    Department of Veterinary Medicine, University of Maryland, College Park, College Park, Maryland, USA.

    Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, Agricultural Research Services, U.S. Department of Agriculture, Ames, Iowa, USA crystal.loving@ars.usda.gov.

    Source

    Clinical and vaccine immunology : CVI 22:10 2015 Oct pg 1109-20

    MeSH

    Administration, Intranasal
    Animals
    Antibodies, Viral
    Cross Protection
    Cross Reactions
    Enzyme-Linked Immunosorbent Assay
    Hemagglutination Inhibition Tests
    Immunoglobulin A
    Influenza A Virus, H1N1 Subtype
    Influenza A Virus, H3N2 Subtype
    Influenza A virus
    Influenza Vaccines
    Mouth
    Nasal Lavage Fluid
    Orthomyxoviridae Infections
    Swine
    Swine Diseases
    Vaccines, Attenuated

    Pub Type(s)

    Evaluation Studies
    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    26291090

    Citation

    Hughes, Holly R., et al. "Oral Fluids as a Live-Animal Sample Source for Evaluating Cross-Reactivity and Cross-Protection Following Intranasal Influenza a Virus Vaccination in Pigs." Clinical and Vaccine Immunology : CVI, vol. 22, no. 10, 2015, pp. 1109-20.
    Hughes HR, Vincent AL, Brockmeier SL, et al. Oral Fluids as a Live-Animal Sample Source for Evaluating Cross-Reactivity and Cross-Protection following Intranasal Influenza A Virus Vaccination in Pigs. Clin Vaccine Immunol. 2015;22(10):1109-20.
    Hughes, H. R., Vincent, A. L., Brockmeier, S. L., Gauger, P. C., Pena, L., Santos, J., ... Loving, C. L. (2015). Oral Fluids as a Live-Animal Sample Source for Evaluating Cross-Reactivity and Cross-Protection following Intranasal Influenza A Virus Vaccination in Pigs. Clinical and Vaccine Immunology : CVI, 22(10), pp. 1109-20. doi:10.1128/CVI.00358-15.
    Hughes HR, et al. Oral Fluids as a Live-Animal Sample Source for Evaluating Cross-Reactivity and Cross-Protection Following Intranasal Influenza a Virus Vaccination in Pigs. Clin Vaccine Immunol. 2015;22(10):1109-20. PubMed PMID: 26291090.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Oral Fluids as a Live-Animal Sample Source for Evaluating Cross-Reactivity and Cross-Protection following Intranasal Influenza A Virus Vaccination in Pigs. AU - Hughes,Holly R, AU - Vincent,Amy L, AU - Brockmeier,Susan L, AU - Gauger,Phillip C, AU - Pena,Lindomar, AU - Santos,Jefferson, AU - Braucher,Douglas R, AU - Perez,Daniel R, AU - Loving,Crystal L, Y1 - 2015/08/19/ PY - 2015/07/01/received PY - 2015/08/13/accepted PY - 2015/8/21/entrez PY - 2015/8/21/pubmed PY - 2016/7/7/medline SP - 1109 EP - 20 JF - Clinical and vaccine immunology : CVI JO - Clin. Vaccine Immunol. VL - 22 IS - 10 N2 - In North American swine, there are numerous antigenically distinct H1 influenza A virus (IAV) variants currently circulating, making vaccine development difficult due to the inability to formulate a vaccine that provides broad cross-protection. Experimentally, live-attenuated influenza virus (LAIV) vaccines demonstrate increased cross-protection compared to inactivated vaccines. However, there is no standardized assay to predict cross-protection following LAIV vaccination. Hemagglutination-inhibiting (HI) antibody in serum is the gold standard correlate of protection following IAV vaccination. LAIV vaccination does not induce a robust serum HI antibody titer; however, a local mucosal antibody response is elicited. Thus, a live-animal sample source that could be used to evaluate LAIV immunogenicity and cross-protection is needed. Here, we evaluated the use of oral fluids (OF) and nasal wash (NW) collected after IAV inoculation as a live-animal sample source in an enzyme-linked immunosorbent assay (ELISA) to predict cross-protection in comparison to traditional serology. Both live-virus exposure and LAIV vaccination provided heterologous protection, though protection was greatest against more closely phylogenetically related viruses. IAV-specific IgA was detected in NW and OF samples and was cross-reactive to representative IAV from each H1 cluster. Endpoint titers of cross-reactive IgA in OF from pigs exposed to live virus was associated with heterologous protection. While LAIV vaccination provided significant protection, LAIV immunogenicity was reduced compared to live-virus exposure. These data suggest that OF from pigs inoculated with wild-type IAV, with surface genes that match the LAIV seed strain, could be used in an ELISA to assess cross-protection and the antigenic relatedness of circulating and emerging IAV in swine. SN - 1556-679X UR - https://www.unboundmedicine.com/medline/citation/26291090/Oral_Fluids_as_a_Live_Animal_Sample_Source_for_Evaluating_Cross_Reactivity_and_Cross_Protection_following_Intranasal_Influenza_A_Virus_Vaccination_in_Pigs_ L2 - http://cvi.asm.org/cgi/pmidlookup?view=long&pmid=26291090 DB - PRIME DP - Unbound Medicine ER -