Antigenic drift and immunity gap explain reduction in protective responses against influenza A(H1N1)pdm09 and A(H3N2) viruses during the COVID-19 pandemic: a cross-sectional study of human sera collected in 2019, 2021, 2022, and 2023
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SUBMITTER: Fossum E
PROVIDER: S-EPMC10916265 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Under selective pressure from the host immune system, antigenic epitopes of influenza virus hemagglutinin (HA) have continually evolved to escape antibody recognition, termed antigenic drift. We analyzed the genomes of influenza A(H3N2) and A(H1N1)pdm09 virus strains circulating in Thailand between 2010 and 2014 and assessed how well the yearly vaccine strains recommended for the southern hemisphere matched them. We amplified and sequenced the HA gene of 120 A(H3N2) and 81 A(H1N1)pdm09 influenza virus samples obtained from respiratory specimens and calculated the perfect-match vaccine efficacy using the pepitope model, which quantitated the antigenic drift in the dominant epitope of HA. Phylogenetic analysis of the A(H3N2) HA1 genes classified most strains into genetic clades 1, 3A, 3B, and 3C. The A(H3N2) strains from the 2013 and 2014 seasons showed very low to moderate vaccine efficacy and demonstrated antigenic drift from epitopes C and A to epitope B. Meanwhile, most A(H1N1)pdm09 strains from the 2012-2014 seasons belonged to genetic clades 6A, 6B, and 6C and displayed the dominant epitope mutations at epitopes B and E. Finally, the vaccine efficacy for A(H1N1)pdm09 (79.6-93.4%) was generally higher than that of A(H3N2). These findings further confirmed the accelerating antigenic drift of the circulating influenza A(H3N2) in recent years.
| S-EPMC4594909 | biostudies-literature
Project description:Seasonal epidemics caused by influenza virus are driven by antigenic changes (drift) in viral surface glycoproteins that allow evasion from preexisting humoral immunity. Antigenic drift is a feature of not only the hemagglutinin (HA), but also of neuraminidase (NA). We have evaluated the antigenic evolution of each protein in H1N1 and H3N2 viruses used in vaccine formulations during the last 15 y by analysis of HA and NA inhibition titers and antigenic cartography. As previously shown for HA, genetic changes in NA did not always lead to an antigenic change. The noncontinuous pattern of NA drift did not correspond closely with HA drift in either subtype. Although NA drift was demonstrated using ferret sera, we show that these changes also impact recognition by NA-inhibiting antibodies in human sera. Remarkably, a single point mutation in the NA of A/Brisbane/59/2007 was primarily responsible for the lack of inhibition by polyclonal antibodies specific for earlier strains. These data underscore the importance of NA inhibition testing to define antigenic drift when there are sequence changes in NA.
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Project description:The influenza A (H1N1) pdm09 virus emerged in 2009 and has been continuously circulating in humans for over ten years. Here, we analyzed a clinical influenza A (H1N1) pdm09-infected patient case hospitalized for two months in Guangdong (from December 14, 2019 to February 15, 2020). This isolate, named A/Guangdong/LCF/2019 (LCF/19), was genetically sequenced, rescued by reverse genetics, and phylogenetically analyzed in the context of other relevant pdm09 isolates. Compared with earlier isolates, this pdm09 virus's genetic sequence contains four substitutions, S186P, T188I, D190A, and Q192E, of the hemagglutinin (HA) segment at position 186-192 (H3 numbering) in the epitope Sb, and two of which are located at the 190-helix. Phylogenetic analysis indicated that the epitope Sb started undergoing a rapid antigenic change in 2018. To characterize the pathogenicity of this novel substitution motif, a panel of reassortant viruses containing the LCF/2019 HA segment or the chimeric HA segment with the four substitutions were rescued. Kinetic growth data revealed that the reassortant viruses, including the LCF/2019 with the PTIAAQE substitution, propagated faster than those rescued ones having the STTADQQ motif in the epitope Sb in Madin-Darby Canine Kidney (MDCK) cells. The HI test showed that the binding activity of escape mutant to 2018 pdm09 sera was weaker than GLW/2018, suggesting that old vaccines might not effectively protect people from infection. Due to the difference in the selection of vaccine strains, people vaccinated in the southern hemisphere could still suffer a severe infection if infected with this antigenic drift pdm09 virus.
| S-EPMC8188537 | biostudies-literature
Project description:Influenza A (H1N1) pdm09 virus emerged in North America in 2009 and has been established as a seasonal strain in humans. After an antigenic stasis of about six years, new antigenically distinct variants of the virus emerged globally in 2016 necessitating a change in the vaccine formulation for the first time in 2017. Herein, we analyzed thirty-eight HA sequences of influenza A (H1N1) pdm09 strains isolated in Kenya during 2015-2018 seasons, to evaluate their antigenic and molecular properties based on the HA1 sub-unit. Our analyses revealed that the A (H1N1) pdm09 strains that circulated in Kenya during this period belonged to genetic clade 6B, subclade 6B.1 and 6B.2. The Kenyan 2015 and 2016 isolates differed from the vaccine strain A/California/07/2009 at nine and fourteen antigenic sites in the HA1 respectively. Further, those isolated in 2017 and 2018 correspondingly varied from A/Michigan/45/2015 vaccine strain at three and fifteen antigenic sites. The predicted vaccine efficacy of A/California/07/2009 against Kenyan 2015/2016 was estimated to be 32.4% while A/Michigan/45/2015 showed estimated vaccine efficacies of 39.6% - 41.8% and 32.4% - 42.1% against Kenyan 2017 and 2018 strains, respectively. Hemagglutination-inhibition (HAI) assay using ferret post-infection reference antiserum showed that the titers for the Kenyan 2015/2016 isolates were 2-8-fold lower compared to the vaccine strain. Overall, our results suggest the A (H1N1) pdm09 viruses that circulated in Kenya during 2015/2016 influenza seasons were antigenic variants of the recommended vaccine strains, denoting sub-optimal vaccine efficacy. Additionally, data generated point to a swiftly evolving influenza A (H1N1) pdm09 virus in recent post pandemic era, underscoring the need for sustained surveillance coupled with molecular and antigenic analyses, to inform appropriate and timely influenza vaccine update.
| S-EPMC7012450 | biostudies-literature
Project description:BACKGROUND: In circulating influenza viruses, gradually accumulated mutations on the glycoprotein hemagglutinin (HA), which interacts with infectivity-neutralizing antibodies, lead to the escape of immune system (called antigenic drift). The antibody recognition is highly correlated to the conformation change on the antigenic sites (epitopes), which locate on HA surface. To quantify a changed epitope for escaping from neutralizing antibodies is the basis for the antigenic drift and vaccine development. RESULTS: We have developed an epitope-based method to identify the antigenic drift of influenza A utilizing the conformation changes on epitopes. A changed epitope, an antigenic site on HA with an accumulated conformation change to escape from neutralizing antibody, can be considered as a "key feature" for representing the antigenic drift. According to hemagglutination inhibition (HI) assays and HA/antibody complex structures, we statistically measured the conformation change of an epitope by considering the number of critical position mutations with high genetic diversity and antigenic scores. Experimental results show that two critical position mutations can induce the conformation change of an epitope to escape from the antibody recognition. Among five epitopes of HA, epitopes A and B, which are near to the receptor binding site, play a key role for neutralizing antibodies. In addition, two changed epitopes often drive the antigenic drift and can explain the selections of 24 WHO vaccine strains. CONCLUSIONS: Our method is able to quantify the changed epitopes on HA for predicting the antigenic variants and providing biological insights to the vaccine updates. We believe that our method is robust and useful for studying influenza virus evolution and vaccine development.
| S-EPMC3044287 | biostudies-literature
Project description:BackgroundInfluenza viruses can cause large seasonal epidemics with high healthcare impact and severity as they continually change their virological properties such as genetic makeup over time.AimWe aimed to monitor the characteristics of circulating influenza viruses over the 2022/23 influenza season in the EU/EEA countries. In addition, we wanted to compare how closely the circulating viruses resemble the viral components selected for seasonal influenza vaccines, and whether the circulating viruses had acquired resistance to commonly used antiviral drugs.MethodsWe performed a descriptive analysis of the influenza virus detections and characterisations reported by National Influenza Centres (NIC) from the 30 EU/EEA countries from week 40/2022 to week 39/2023 to The European Surveillance System (TESSy) as part of the Global Influenza Surveillance and Response System (GISRS).ResultsIn the EU/EEA countries, the 2022/23 influenza season was characterised by co-circulation of A(H1N1)pdm09, A(H3N2) and B/Victoria-lineage viruses. The genetic evolution of these viruses continued and clade 6B.1A.5a.2a of A(H1N1)pdm09, 3C.2a1b.2a.2b of A(H3N2) and V1A.3a.2 of B/Victoria viruses dominated. Influenza B/Yamagata-lineage viruses were not reported.DiscussionThe World Health Organization (WHO) vaccine composition recommendation for the northern hemisphere 2023/24 season reflects the European virus evolution, with a change of the A(H1N1)pdm09 component, while keeping the A(H3N2) and B/Victoria-lineage components unchanged.
| S-EPMC11484342 | biostudies-literature
Project description:In February and September each year the World Health Organisation (WHO) recommends influenza viruses to be included in influenza vaccines for the forthcoming winters in the Northern and Southern Hemispheres respectively. These recommendations are based on data collected by National Influenza Centres (NIC) through the Global Influenza Surveillance and Response System (GISRS) and a more detailed analysis of representative and potential antigenically variant influenza viruses from the WHO Collaborating Centres for Influenza (WHO CCs) and Essential Regulatory Laboratories (ERLs). This article provides a detailed summary of the antigenic and genetic properties of viruses and additional background data used by WHO experts during development of the recommendations for the 2012 Southern Hemisphere influenza vaccine composition.
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Project description:UnlabelledThe majority of currently circulating influenza A(H1N1) viruses are antigenically similar to the virus that caused the 2009 influenza pandemic. However, antigenic variants are expected to emerge as population immunity increases. Amino acid substitutions in the hemagglutinin protein can result in escape from neutralizing antibodies, affect viral fitness, and change receptor preference. In this study, we constructed mutants with substitutions in the hemagglutinin of A/Netherlands/602/09 in an attenuated backbone to explore amino acid changes that may contribute to emergence of antigenic variants in the human population. Our analysis revealed that single substitutions affecting the loop that consists of amino acid positions 151 to 159 located adjacent to the receptor binding site caused escape from ferret and human antibodies elicited after primary A(H1N1)pdm09 virus infection. The majority of these substitutions resulted in similar or increased replication efficiency in vitro compared to that of the virus carrying the wild-type hemagglutinin and did not result in a change of receptor preference. However, none of the substitutions was sufficient for escape from the antibodies in sera from individuals that experienced both seasonal and pandemic A(H1N1) virus infections. These results suggest that antibodies directed against epitopes on seasonal A(H1N1) viruses contribute to neutralization of A(H1N1)pdm09 antigenic variants, thereby limiting the number of possible substitutions that could lead to escape from population immunity.ImportanceInfluenza A viruses can cause significant morbidity and mortality in humans. Amino acid substitutions in the hemagglutinin protein can result in escape from antibody-mediated neutralization. This allows the virus to reinfect individuals that have acquired immunity to previously circulating strains through infection or vaccination. To date, the vast majority of A(H1N1)pdm09 strains remain antigenically similar to the virus that caused the 2009 influenza pandemic. However, antigenic variants are expected to emerge as a result of increasing population immunity. We show that single amino acid substitutions near the receptor binding site were sufficient to escape from antibodies specific for A(H1N1)pdm09 viruses but not from antibodies elicited in response to infections with seasonal A(H1N1) and A(H1N1)pdm09 viruses. This study identified substitutions in A(H1N1)pdm09 viruses that support escape from population immunity but also suggested that the number of potential escape variants is limited by previous exposure to seasonal A(H1N1) viruses.
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Project description:Influenza viruses continually evolve new antigenic variants, through mutations in epitopes of their major surface proteins, hemagglutinin (HA) and neuraminidase (NA). Antigenic drift potentiates the reinfection of previously infected individuals, but the contribution of this process to variability in annual epidemics is not well understood. Here we link influenza A(H3N2) virus evolution to regional epidemic dynamics in the United States during 1997-2019. We integrate phenotypic measures of HA antigenic drift and sequence-based measures of HA and NA fitness to infer antigenic and genetic distances between viruses circulating in successive seasons. We estimate the magnitude, severity, timing, transmission rate, age-specific patterns, and subtype dominance of each regional outbreak and find that genetic distance based on broad sets of epitope sites is the strongest evolutionary predictor of A(H3N2) virus epidemiology. Increased HA and NA epitope distance between seasons correlates with larger, more intense epidemics, higher transmission, greater A(H3N2) subtype dominance, and a greater proportion of cases in adults relative to children, consistent with increased population susceptibility. Based on random forest models, A(H1N1) incidence impacts A(H3N2) epidemics to a greater extent than viral evolution, suggesting that subtype interference is a major driver of influenza A virus infection dynamics, presumably via heterosubtypic cross-immunity.
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Project description:Influenza viruses continually evolve new antigenic variants, through mutations in epitopes of their major surface proteins, hemagglutinin (HA) and neuraminidase (NA). Antigenic drift potentiates the reinfection of previously infected individuals, but the contribution of this process to variability in annual epidemics is not well understood. Here, we link influenza A(H3N2) virus evolution to regional epidemic dynamics in the United States during 1997-2019. We integrate phenotypic measures of HA antigenic drift and sequence-based measures of HA and NA fitness to infer antigenic and genetic distances between viruses circulating in successive seasons. We estimate the magnitude, severity, timing, transmission rate, age-specific patterns, and subtype dominance of each regional outbreak and find that genetic distance based on broad sets of epitope sites is the strongest evolutionary predictor of A(H3N2) virus epidemiology. Increased HA and NA epitope distance between seasons correlates with larger, more intense epidemics, higher transmission, greater A(H3N2) subtype dominance, and a greater proportion of cases in adults relative to children, consistent with increased population susceptibility. Based on random forest models, A(H1N1) incidence impacts A(H3N2) epidemics to a greater extent than viral evolution, suggesting that subtype interference is a major driver of influenza A virus infection ynamics, presumably via heterosubtypic cross-immunity.
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