Substitutions near the hemagglutinin receptor-binding site determine the antigenic evolution of influenza A H3N2 viruses in U.S. swine

Swine influenza A virus is an endemic and economically important pathogen in pigs, with the potential to infect other host species. The hemagglutinin (HA) protein is the primary target of protective immune responses and the major component in swine influenza A vaccines. However, as a result of antigenic drift, vaccine strains must be regularly updated to reflect currently circulating strains. Characterizing the cross-reactivity between strains in pigs and seasonal influenza virus strains in humans is also important in assessing the relative risk of interspecies transmission of viruses from one host population to the other. Hemagglutination inhibition (HI) assay data for swine and human H3N2 viruses were used with antigenic cartography to quantify the antigenic differences among H3N2 viruses isolated from pigs in the United States from 1998 to 2013 and the relative cross-reactivity between these viruses and current human seasonal influenza A virus strains. Two primary antigenic clusters were found circulating in the pig population, but with enough diversity within and between the clusters to suggest updates in vaccine strains are needed. We identified single amino acid substitutions that are likely responsible for antigenic differences between the two primary antigenic clusters and between each antigenic cluster and outliers. The antigenic distance between current seasonal influenza virus H3 strains in humans and those endemic in swine suggests that population immunity may not prevent the introduction of human viruses into pigs, and possibly vice versa, reinforcing the need to monitor and prepare for potential incursions

Further evidence of the circulation of PMV-4 and influenza viruses with N2 - 1957 enzyme in migratory waterfowls

I n the years 1980—1984, one paramyxovirus type 4 and 11 influenza viruses were isolated from cloacal swabs collected from migratory waterfowls in Fed. Rep. Germany. One influenza virus of H4N8 subtype was isolated from swabs of commercial ducks collected at an abbatoir. Seven of 10 influenza strains, isolated from mallard clucks and coot were identified as a mixture of 2 —3 strains of H l , H4, and Ho subtype; 3 virus strains from the same locality relate antigenically to subtype H4 w i t h enzyme serologically identical with N2 — Singapore/57 as demonstrated by means of polyclonal and monoclonal antibody

Integrating influenza antigenic dynamics with molecular evolution.

Influenza viruses undergo continual antigenic evolution allowing mutant viruses to evade host immunity acquired to previous virus strains. Antigenic phenotype is often assessed through pairwise measurement of cross-reactivity between influenza strains using the hemagglutination inhibition (HI) assay. Here, we extend previous approaches to antigenic cartography, and simultaneously characterize antigenic and genetic evolution by modeling the diffusion of antigenic phenotype over a shared virus phylogeny. Using HI data from influenza lineages A/H3N2, A/H1N1, B/Victoria and B/Yamagata, we determine patterns of antigenic drift across viral lineages, showing that A/H3N2 evolves faster and in a more punctuated fashion than other influenza lineages. We also show that year-to-year antigenic drift appears to drive incidence patterns within each influenza lineage. This work makes possible substantial future advances in investigating the dynamics of influenza and other antigenically-variable pathogens by providing a model that intimately combines molecular and antigenic evolution. DOI: http://dx.doi.org/10.7554/eLife.01914.001

Simulations of Antigenic Variability in Influenza A

Computational models of the immune system (IS) and pathogenic agents have several applications, such as theory testing and validation, or as a complement to first stages of drug trials. One possible application is the prediction of the lethality of new Influenza A strains, which are constantly created due to antigenic drift and shift. Here, we present several simulations of antigenic variability in Influenza A using an agent-based approach, where low level molecular antigen-antibody interactions are explicitly described. Antigenic drift and shift events are analyzed regarding the virulence of emergent strains against the IS. Results are discussed from a qualitative point of view taking into account recent and generally recognized immunology and influenza literature

Genetic characterization of influenza A(H3N2) viruses circulating in coastal Kenya, 2009-2017

Background Influenza viruses evolve rapidly and undergo immune driven selection, especially in the hemagglutinin (HA) protein. We report amino acid changes affecting antigenic epitopes and receptor‐binding sites of A(H3N2) viruses circulating in Kilifi, Kenya, from 2009 to 2017. Methods Next‐generation sequencing (NGS) was used to generate A(H3N2) virus genomic data from influenza‐positive specimens collected from hospital admissions and health facility outpatients presenting with acute respiratory illness to health facilities within the Kilifi Health and Demographic Surveillance System. Full‐length HA sequences were utilized to characterize A(H3N2) virus genetic and antigenic changes. Results From 186 (90 inpatient and 96 outpatient) influenza A virus‐positive specimens processed, 101 A(H3N2) virus whole genomes were obtained. Among viruses identified in inpatient specimens from 2009 to 2015, divergence of circulating A(H3N2) viruses from the vaccine strains A/Perth/16/2009, A/Texas/50/2012, and A/Switzerland/9715293/2013 formed 6 genetic clades (A/Victoria/208/2009‐like, 3B, 3C, 3C.2a, 4, and 7). Among viruses identified in outpatient specimens from 2015 to 2017, divergence of circulating A(H3N2) viruses from vaccine strain A/Hong Kong/4801/2014 formed clade 3C.2a, subclades 3C.2a2 and 3C.2a3, and subgroup 3C.2a1b. Several amino acid substitutions were associated with the continued genetic evolution of A(H3N2) strains in circulation. Conclusions Our results suggest continuing evolution of currently circulating A(H3N2) viruses in Kilifi, coastal Kenya and suggest the need for continuous genetic and antigenic viral surveillance of circulating seasonal influenza viruses with broad geographic representation to facilitate prompt and efficient selection of influenza strains for inclusion in future influenza vaccines

Heterologous prime-boost vaccination with H3N2 influenza viruses of swine favors cross-clade antibody responses and protection

The emergence of multiple novel lineages of H1 and H3 influenza A viruses in swine has confounded control by inactivated vaccines. Because of substantial genetic and geographic heterogeneity among circulating swine influenza viruses, one vaccine strain per subtype cannot be efficacious against all of the current lineages. We have performed vaccination-challenge studies in pigs to examine whether priming and booster vaccinations with antigenically distinct H3N2 swine influenza viruses could broaden antibody responses and protection. We prepared monovalent whole inactivated, adjuvanted vaccines based on a European and a North American H3N2 swine influenza virus, which showed 81.5% aa homology in the HA1 region of the hemagglutinin and 83.4% in the neuraminidase. Our data show that (i) Priming with European and boosting with North American H3N2 swine influenza virus induces antibodies and protection against both vaccine strains, unlike prime-boost vaccination with a single virus or a single administration of bivalent vaccine. (ii) The heterologous prime-boost vaccination enhances hemagglutination inhibiting, virus neutralizing and neuraminidase inhibiting antibody responses against H3N2 viruses that are antigenically distinct from both vaccine strains. Antibody titers to the most divergent viruses were higher than after two administrations of bivalent vaccine. (iii) However, it does not induce antibodies to the conserved hemagglutinin stalk or to other hemagglutinin subtypes. We conclude that heterologous prime-boost vaccination might broaden protection to H3N2 swine influenza viruses and reduce the total amount of vaccine needed. This strategy holds potential for vaccination against influenza viruses from both humans and swine and for a better control of (reverse) zoonotic transmission of influenza viruses