Impact of Prior Seasonal H3N2 Influenza Vaccination or Infection on Protection and Transmission of Emerging Variants of Influenza A(H3N2)v Virus in Ferrets

Houser, Katherine V.; Pearce, Melissa B.; Katz, Jacqueline M.; Tumpey, Terrence M.

doi:10.1128/jvi.02434-13

Cited by 51 publications

(51 citation statements)

References 33 publications

(54 reference statements)

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“…Serological studies with human serum samples demonstrate that while a significant proportion of adolescents and young adults have cross-reactive antibodies against A(H3N2)v viruses, young children lack such preexisting immunity (35,36). Investigations in the ferret model suggest that vaccination with seasonal trivalent inactivated influenza vaccines does not provide protection against transmission of A(H3N2)v virus (37,38). These findings highlight the antigenic difference between circulating H3N2 and the swine-origin viruses and the need to evaluate and approve A(H3N2)v vaccines.…”

Section: Discussionmentioning

confidence: 92%

Amino Acids in Hemagglutinin Antigenic Site B Determine Antigenic and Receptor Binding Differences between A(H3N2)v and Ancestral Seasonal H3N2 Influenza Viruses

Wang

Ilyushina

Lugovtsev

et al. 2017

J Virol

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Influenza A H3N2 variant [A(H3N2)v] viruses, which have caused human infections in the UnitedStates in recent years, originated from human seasonal H3N2 viruses that were introduced into North American swine in the mid-1990s, but they are antigenically distinct from both the ancestral and current circulating H3N2 strains. A reference A(H3N2)v virus, A/Minnesota/11/2010 (MN/10), and a seasonal H3N2 strain, A/Beijing/32/1992 (BJ/92), were chosen to determine the molecular basis for the antigenic difference between A(H3N2)v and the ancestral viruses. Viruses containing wild-type and mutant MN/10 or BJ/92 hemagglutinins (HAs) were constructed and probed for reactivity with ferret antisera against MN/10 and BJ/92 in hemagglutination inhibition assays. Among the amino acids that differ between the MN/10 and BJ/92 HAs, those in antigenic site A had little impact on the antigenic phenotype. Within antigenic site B, mutations at residues 156, 158, 189, and 193 of MN/10 HA to those in BJ/92 switched the MN/10 antigenic phenotype to that of BJ/ 92. Mutations at residues 156, 157, 158, 189, and 193 of BJ/92 HA to amino acids present in MN/10 were necessary for BJ/92 to become antigenically similar to MN/ 10. The HA amino acid substitutions responsible for switching the antigenic phenotype also impacted HA binding to sialyl receptors that are usually present in the human respiratory tract. Our study demonstrates that antigenic site B residues play a critical role in determining both the unique antigenic phenotype and receptor specificity of A(H3N2)v viruses, a finding that may facilitate future surveillance and risk assessment of novel influenza viruses. IMPORTANCE Influenza A H3N2 variant [A(H3N2)v] viruses have caused hundreds of human infections in multiple states in the UnitedStates since 2009. Most cases have been children who had contact with swine in agricultural fairs. These viruses originated from human seasonal H3N2 viruses that were introduced into the U.S. swine population in the mid-1990s, but they are different from both these ancestral viruses and current circulating human seasonal H3N2 strains in terms of their antigenic characteristics as measured by hemagglutination inhibition (HI) assay. In this study, we identified amino acids in antigenic site B of the surface glycoprotein hemagglutinin (HA) that explain the antigenic difference between A(H3N2)v and the ancestral H3N2 strains. These amino acid mutations also alter binding to minor human-type glycans, suggesting that host adaptation may contribute to the selection of antigenically distinct H3N2 variants which pose a threat to public health.

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Section: Discussionmentioning

confidence: 92%

Amino Acids in Hemagglutinin Antigenic Site B Determine Antigenic and Receptor Binding Differences between A(H3N2)v and Ancestral Seasonal H3N2 Influenza Viruses

Wang

Ilyushina

Lugovtsev

et al. 2017

J Virol

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“…In contrast, LAIV-vaccinated pigs challenged with IL/10(␥) demonstrated reduced virus replication in the nose that was cleared by 4 dpi. These reductions in nasal shedding in vaccinated, challenged animals suggests that LAIV vaccination could limit the transmission of heterologous virus to naive or vaccinated contact animals (38,56,57), thus slowing or breaking the transmission cycle. Studies are under way to investigate this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

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

Hughes

Vincent

Brockmeier

et al. 2015

Clin Vaccine Immunol

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cIn 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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“…Factors that were controlled in our experiments but vary in nature are known to affect the frequency and timing of dual-transmission events. For example, temperature and humidity (60)(61)(62), preexisting immunity (63)(64)(65)(66), timing and duration of exposure (67), proximity of exposure (68), host species (69), and viral fitness in that host species (41,(70)(71)(72)(73) all impact transmission efficiency and are therefore expected to dictate the likelihood of two independent transmission events leading to coinfection.…”

Section: Discussionmentioning

confidence: 99%

Influenza A Virus Coinfection through Transmission Can Support High Levels of Reassortment

Tao

White

et al. 2015

J Virol

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The reassortment of gene segments between influenza viruses increases genomic diversity and plays an important role in viral evolution. We have shown previously that this process is highly efficient within a coinfected cell and, given synchronous coinfection at moderate or high doses, can give rise to ϳ60 to 70% of progeny shed from an animal host. Conversely, reassortment in vivo can be rendered undetectable by lowering viral doses or extending the time between infections. One might also predict that seeding of transmitted viruses into different sites within the target tissue could limit subsequent reassortment. Given the potential for stochastic factors to restrict reassortment during natural infection, we sought to determine its efficiency in a host coinfected through transmission. Two scenarios were tested in a guinea pig model, using influenza A/Panama/2007/99 (H3N2) virus (wt) and a silently mutated variant (var) thereof as parental virus strains. In the first, coinfection was achieved by exposing a naive guinea pig to two cagemates, one infected with wt and the other with var virus. When such exposure led to coinfection, robust reassortment was typically seen, with 50 to 100% of isolates carrying reassortant genomes at one or more time points. In the second scenario, naive guinea pigs were exposed to a cagemate that had been coinoculated with wt and var viruses. Here, reassortment occurred in the coinoculated donor host, multiple variants were transmitted, and reassortants were prevalent in the recipient host. Together, these results demonstrate the immense potential for reassortment to generate viral diversity in nature. IMPORTANCE Influenza viruses evolve rapidly under selection due to the generation of viral diversity through two mechanisms. The first is the introduction of random errors into the genome by the viral polymerase, which occurs with a frequency of approximately 10؊5 errors/nucleotide replicated. The second is reassortment, or the exchange of gene segments between viruses. Reassortment is known to occur readily under well-controlled laboratory conditions, but its frequency in nature is not clear. Here, we tested the hypothesis that reassortment efficiency following coinfection through transmission would be reduced compared to that seen with coinoculation. Contrary to this hypothesis, our results indicate that coinfection achieved through transmission supports high levels of reassortment. These results suggest that reassortment is not exquisitely sensitive to stochastic effects associated with transmission and likely occurs in nature whenever a host is infected productively with more than one influenza A virus.T he segmented nature of the influenza virus genome allows for ready exchange of genetic material between two viruses that coinfect one cell (1). If the parental viruses differ in all eight gene segments, 256 different progeny viruses can be produced in a single reassortment event. Reassortment between two very distinct strains is typically associated with marked genotypic and ...

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Impact of Prior Seasonal H3N2 Influenza Vaccination or Infection on Protection and Transmission of Emerging Variants of Influenza A(H3N2)v Virus in Ferrets

Cited by 51 publications

References 33 publications

Amino Acids in Hemagglutinin Antigenic Site B Determine Antigenic and Receptor Binding Differences between A(H3N2)v and Ancestral Seasonal H3N2 Influenza Viruses

Amino Acids in Hemagglutinin Antigenic Site B Determine Antigenic and Receptor Binding Differences between A(H3N2)v and Ancestral Seasonal H3N2 Influenza Viruses

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

Influenza A Virus Coinfection through Transmission Can Support High Levels of Reassortment

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