Dataset Information

Impaired Vaccine-Induced Antibody Response Against Clade 6B H1N1 Viruses in Individuals Before Viral Emergence.

ABSTRACT:

Background

Clade 6B H1N1 pdm09 influenza viruses cause substantial morbidity and mortality worldwide. Human antibody profiles elicited upon vaccination against the clade 6B virus are largely unclear before viral emergence.

Methods

Healthy volunteers, including children aged 3-8 years, adolescents aged 9-17 years, and adults, were enrolled before the clade 6B H1N1 outbreak and received the 2013-2014 inactivated influenza vaccine. We determined antibody responses before and after vaccination. Vaccine-induced plasmablast-derived antibodies were tested against H1N1 pdm09 reference and clade 6B viruses.

Results

The majority of the subjects generated robust hemagglutination inhibition and neutralizing antibody responses upon vaccination across the different age groups. Nevertheless, a subset of young adults preferentially produced antibodies that failed to neutralize clade 6B viruses that emerged and circulated in 2014-2016. The hemagglutinin K163Q change at the Sa antigenic site, one of the substitutions that define clade 6B viruses, was responsible for resistance to neutralization by both postvaccination sera and vaccine-induced plasmablast-derived antibodies.

Conclusions

Vaccine-induced antibody immunity is compromised by the antigenic change of H1N1 pdm09 virus in a subset of adults, and this may warrant the incorporation of human serology in the antigenic characterization of virus and vaccine strain selection.

SUBMITTER: Huang KA

PROVIDER: S-EPMC6954487 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

Impaired Vaccine-Induced Antibody Response Against Clade 6B H1N1 Viruses in Individuals Before Viral Emergence.

Huang Kuan-Ying A KA Huang Yhu-Chering YC Chiu Cheng-Hsun CH Tsao Kuo-Chien KC Lin Tzou-Yien TY

Open forum infectious diseases 20200111 1

<h4>Background</h4>Clade 6B H1N1 pdm09 influenza viruses cause substantial morbidity and mortality worldwide. Human antibody profiles elicited upon vaccination against the clade 6B virus are largely unclear before viral emergence.<h4>Methods</h4>Healthy volunteers, including children aged 3-8 years, adolescents aged 9-17 years, and adults, were enrolled before the clade 6B H1N1 outbreak and received the 2013-2014 inactivated influenza vaccine. We determined antibody responses before and after va ...[more]

PMID: 31950072

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Project description:Surveillance for emerging human influenza virus clades is important for identifying changes in viral fitness and assessing antigenic similarity to vaccine strains. While fitness and antigenic structure are both important aspects of virus success, they are distinct characteristics and do not always change in a complementary manner. The 2019-2020 Northern Hemisphere influenza season saw the emergence of two H1N1 clades: A5a.1 and A5a.2. While several studies indicated that A5a.2 showed similar or even increased antigenic drift compared with A5a.1, the A5a.1 clade was still the predominant circulating clade that season. Clinical isolates of representative viruses from these clades were collected in Baltimore, Maryland during the 2019-2020 season and multiple assays were performed to compare both antigenic drift and viral fitness between clades. Neutralization assays performed on serum from healthcare workers pre- and post-vaccination during the 2019-2020 season show a comparable drop in neutralizing titers against both A5a.1 and A5a.2 viruses compared with the vaccine strain, indicating that A5a.1 did not have antigenic advantages over A5a.2 that would explain its predominance in this population. Plaque assays were performed to investigate fitness differences, and the A5a.2 virus produced significantly smaller plaques compared with viruses from A5a.1 or the parental A5a clade. To assess viral replication, low MOI growth curves were performed on both MDCK-SIAT and primary differentiated human nasal epithelial cell cultures. In both cell cultures, A5a.2 yielded significantly reduced viral titers at multiple timepoints post-infection compared with A5a.1 or A5a. Receptor binding was then investigated through glycan array experiments which showed a reduction in receptor binding diversity for A5a.2, with fewer glycans bound and a higher percentage of total binding attributable to the top three highest bound glycans. Together these data indicate that the A5a.2 clade had a reduction in viral fitness, including reductions in receptor binding, that may have contributed to the limited prevalence observed after emergence.

Project description:Surveillance for emerging human influenza virus clades is important for identifying changes in viral fitness and assessing antigenic similarity to vaccine strains. While fitness and antigenic structure are both important aspects of virus success, they are distinct characteristics and do not always change in a complementary manner. The 2019-20 Northern Hemisphere influenza season saw the emergence of two H1N1 clades: A5a.1 and A5a.2. While several studies indicated that A5a.2 showed similar or even increased antigenic drift compared with A5a.1, the A5a.1 clade was still the predominant circulating clade that season. Clinical isolates of representative viruses from these clades were collected in Baltimore, Maryland during the 2019-20 season and multiple assays were performed to compare both antigenic drift and viral fitness between clades. Neutralization assays performed on serum from healthcare workers pre- and post-vaccination during the 2019-20 season show a comparable drop in neutralizing titers against both A5a.1 and A5a.2 viruses compared with the vaccine strain, indicating that A5a.1 did not have antigenic advantages over A5a.2 that would explain its predominance in this population. Plaque assays were performed to investigate fitness differences, and the A5a.2 virus produced significantly smaller plaques compared with viruses from A5a.1 or the parental A5a clade. To assess viral replication, low MOI growth curves were performed on both MDCK-SIAT and primary differentiated human nasal epithelial cell cultures. In both cell cultures, A5a.2 yielded significantly reduced viral titers at multiple timepoints post-infection compared with A5a.1 or A5a. Receptor binding was then investigated through glycan array experiments which showed a reduction in receptor binding diversity for A5a.2, with fewer glycans bound and a higher percentage of total binding attributable to the top three highest bound glycans. Together these data indicate that the A5a.2 clade had a reduction in viral fitness, including reductions in receptor binding, that may have contributed to the limited prevalence observed after emergence.

Dataset Information

Impaired Vaccine-Induced Antibody Response Against Clade 6B H1N1 Viruses in Individuals Before Viral Emergence.

Background

Methods

Results

Conclusions

Publications

Impaired Vaccine-Induced Antibody Response Against Clade 6B H1N1 Viruses in Individuals Before Viral Emergence.

Similar Datasets

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