Swine influenza virus vaccine serologic cross‐reactivity to contemporary <scp>US</scp> swine H3N2 and efficacy in pigs infected with an H3N2 similar to 2011–2012 H3N2v

Kitikoon, Pravina; Gauger, Phillip C.; Anderson, Tavis K.; Culhane, Marie; Swenson, Sabrina L.; Loving, Crystal L.; Pérez, Daniel R.; Vincent, Amy L.

doi:10.1111/irv.12189

Cited by 35 publications

(32 citation statements)

References 32 publications

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“…In contrast, WIV provided only partial protection against mismatched strains and was associated with the risk of enhanced disease. This observation is consistent with other findings that have examined the vaccine efficacies of WIV and LAIV in pigs in side-byside comparisons (33,37,38). Of interest, an LAIV distinct from the one used in the studies presented here has recently been approved for use in swine in the United States (24,25,39) and may provide broader protection, but the H3 strain in the commercial LAIV is of a different phylogenetic clade and further study is required to speculate on its capacity for protection from the contemporary strains tested here.…”

Section: Discussionsupporting

confidence: 93%

“…In study 1, both vaccine platforms with a cyan-antigenic-cluster virus provided significant protection against a red-antigenic-cluster challenge virus. OH/04, a wellcharacterized virus that has been used previously in vaccine studies (32,33) and characterized antigenically to be within the cyan antigenic cluster (13), was chosen as the vaccine antigen. IN/13, a contemporary virus that was recently examined in an animal study (30), contains a red antigenic cluster motif, and it was selected as the challenge strain.…”

Section: Discussionmentioning

confidence: 99%

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Comparison of Adjuvanted-Whole Inactivated Virus and Live-Attenuated Virus Vaccines against Challenge with Contemporary, Antigenically Distinct H3N2 Influenza A Viruses

Abente

Rajão

Santos

et al. 2018

J Virol

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Influenza A viruses in swine (IAV-S) circulating in the United States of America are phylogenetically and antigenically distinct. A human H3 hemagglutinin (HA) was introduced into the IAV-S gene pool in the late 1990s, sustained continued circulation, and evolved into five monophyletic genetic clades, H3 clades IV-A to -E, after 2009. Across these phylogenetic clades, distinct antigenic clusters were identified, with three clusters (cyan, red, and green antigenic cluster) among the most frequently detected antigenic phenotypes (Abente EJ, Santos J, Lewis NS, Gauger PC, Stratton J, et al. J Virol 90:8266-8280, 2016, https://doi.org/10.1128/JVI.01002-16). Although it was demonstrated that antigenic diversity of H3N2 IAV-S was associated with changes at a few amino acid positions in the head of the HA, the implications of this diversity for vaccine efficacy were not tested. Using antigenically representative H3N2 viruses, we compared whole inactivated virus (WIV) and live-attenuated influenza virus (LAIV) vaccines for protection against challenge with antigenically distinct H3N2 viruses in pigs. WIV provided partial protection against antigenically distinct viruses but did not prevent virus replication in the upper respiratory tract. In contrast, LAIV provided complete protection from disease and virus was not detected after challenge with antigenically distinct viruses. Due to the rapid evolution of the influenza A virus, vaccines require continuous strain updates. Additionally, the platform used to deliver the vaccine can have an impact on the breadth of protection. Currently, there are various vaccine platforms available to prevent influenza A virus infection in swine, and we experimentally tested two: adjuvanted-whole inactivated virus and live-attenuated virus. When challenged with an antigenically distinct virus, adjuvanted-whole inactivated virus provided partial protection, while live-attenuated virus provided effective protection. Additional strategies are required to broaden the protective properties of inactivated virus vaccines, given the dynamic antigenic landscape of cocirculating strains in North America, whereas live-attenuated vaccines may require less frequent strain updates, based on demonstrated cross-protection. Enhancing vaccine efficacy to control influenza infections in swine will help reduce the impact they have on swine production and reduce the risk of swine-to-human transmission.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Comparison of Adjuvanted-Whole Inactivated Virus and Live-Attenuated Virus Vaccines against Challenge with Contemporary, Antigenically Distinct H3N2 Influenza A Viruses

Abente

Rajão

Santos

et al. 2018

J Virol

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“…Experimental data suggest that the protection provided by commercial killed vaccines against contemporary IAV-S is limited (49,50). Importantly, the USDA Center for Veterinary Biologics implemented a new licensure policy in 2007 that allows vaccine manufacturers to update vaccine strains more rapidly under a currently approved licensing agreement (51).…”

Section: Discussionmentioning

confidence: 99%

The Molecular Determinants of Antibody Recognition and Antigenic Drift in the H3 Hemagglutinin of Swine Influenza A Virus

Abente

Santos

Lewis

et al. 2016

J Virol

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Influenza A virus (IAV) of the H3 subtype is an important respiratory pathogen that affects both humans and swine. Vaccination to induce neutralizing antibodies against the surface glycoprotein hemagglutinin (HA) is the primary method used to control disease. However, due to antigenic drift, vaccine strains must be periodically updated. Six of the 7 positions previously identified in human seasonal H3 (positions 145, 155, 156, 158, 159, 189, and 193) were also indicated in swine H3 antigenic evolution. To experimentally test the effect on virus antigenicity of these 7 positions, substitutions were introduced into the HA of an isogenic swine lineage virus. We tested the antigenic effect of these introduced substitutions by using hemagglutination inhibition (HI) data with monovalent swine antisera and antigenic cartography to evaluate the antigenic phenotype of the mutant viruses. Combinations of substitutions within the antigenic motif caused significant changes in antigenicity. One virus mutant that varied at only two positions relative to the wild type had a >4-fold reduction in HI titers compared to homologous antisera. Potential changes in pathogenesis and transmission of the double mutant were evaluated in pigs. Although the double mutant had virus shedding titers and transmissibility comparable to those of the wild type, it caused a significantly lower percentage of lung lesions. Elucidating the antigenic effects of specific amino acid substitutions at these sites in swine H3 IAV has important implications for understanding IAV evolution within pigs as well as for improved vaccine development and control strategies in swine. IMPORTANCEA key component of influenza virus evolution is antigenic drift mediated by the accumulation of amino acid substitutions in the hemagglutinin (HA) protein, resulting in escape from prior immunity generated by natural infection or vaccination. Understanding which amino acid positions of the HA contribute to the ability of the virus to avoid prior immunity is important for understanding antigenic evolution and informs vaccine efficacy predictions based on the genetic sequence data from currently circulating strains. Following our previous work characterizing antigenic phenotypes of contemporary wild-type swine H3 influenza viruses, we experimentally validated that substitutions at 6 amino acid positions in the HA protein have major effects on antigenicity. An improved understanding of the antigenic diversity of swine influenza will facilitate a rational approach for selecting more effective vaccine components to control the circulation of influenza in pigs and reduce the potential for zoonotic viruses to emerge. I nfluenza A virus (IAV) of the H3 subtype is an important pathogen that infects both humans and swine. The main strategy used to prevent or reduce morbidity of IAV in humans is the implementation of vaccine programs (1). Likewise, swine producers employ commercially available and farm-specific autogenous vaccines to prevent IAV clinical disease in swine (2, 3). ...

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“…Subtypes containing H1 also exhibited a high rate of divergence and are currently classified into clusters ␣, ␤, ␥ and ␦. The emergence of the 2009 H1N1 pandemic virus (H1N1 pdm09) and its subsequent reassortments with the recent H3N2 variant increased the antigenic variation of SIV [4][5][6][7]. A combination of some of the HA gene alleles and TRIG cassettes might be contributing towards survival and propagation of emerging SIV variants in pigs [8].…”

Section: Introductionmentioning

confidence: 99%

Poly I:C adjuvanted inactivated swine influenza vaccine induces heterologous protective immunity in pigs

Thomas

Wang

Sreenivasan

et al. 2015

Vaccine

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Swine influenza is widely prevalent in swine herds in North America and Europe causing enormous economic losses and a public health threat. Pigs can be infected by both avian and mammalian influenza viruses and are sources of generation of reassortant influenza viruses capable of causing pandemics in humans. Current commercial vaccines provide satisfactory immunity against homologous viruses; however, protection against heterologous viruses is not adequate. In this study, we evaluated the protective efficacy of an intranasal Poly I:C adjuvanted UV inactivated bivalent swine influenza vaccine consisting of Swine/OH/24366/07 H1N1 and Swine/CO/99 H3N2, referred as PAV, in maternal antibody positive pigs against an antigenic variant and a heterologous swine influenza virus challenge. Groups of three-week-old commercial-grade pigs were immunized intranasally with PAV or a commercial vaccine (CV) twice at 2 weeks intervals. Three weeks after the second immunization, pigs were challenged with the antigenic variant Swine/MN/08 H1N1 (MN08) and the heterologous Swine/NC/10 H1N2 (NC10) influenza virus. Antibodies in serum and respiratory tract, lung lesions, virus shedding in nasal secretions and virus load in lungs were assessed. Intranasal administration of PAV induced challenge viruses specific-hemagglutination inhibition- and IgG antibodies in the serum and IgA and IgG antibodies in the respiratory tract. Importantly, intranasal administration of PAV provided protection against the antigenic variant MN08 and the heterologous NC10 swine influenza viruses as evidenced by significant reductions in lung virus load, gross lung lesions and significantly reduced shedding of challenge viruses in nasal secretions. These results indicate that Poly I:C or its homologues may be effective as vaccine adjuvants capable of generating cross-protective immunity against antigenic variants/heterologous swine influenza viruses in pigs.

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Swine influenza virus vaccine serologic cross‐reactivity to contemporary US swine H3N2 and efficacy in pigs infected with an H3N2 similar to 2011–2012 H3N2v

Cited by 35 publications

References 32 publications

Comparison of Adjuvanted-Whole Inactivated Virus and Live-Attenuated Virus Vaccines against Challenge with Contemporary, Antigenically Distinct H3N2 Influenza A Viruses

Comparison of Adjuvanted-Whole Inactivated Virus and Live-Attenuated Virus Vaccines against Challenge with Contemporary, Antigenically Distinct H3N2 Influenza A Viruses

The Molecular Determinants of Antibody Recognition and Antigenic Drift in the H3 Hemagglutinin of Swine Influenza A Virus

Poly I:C adjuvanted inactivated swine influenza vaccine induces heterologous protective immunity in pigs

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