Dataset Information

Cell-Mediated Immunity Against Antigenically Drifted Influenza A(H3N2) Viruses in Children During a Vaccine Mismatch Season.

ABSTRACT:

Background

Emergence of antigenically drifted influenza A(H3N2) viruses resulted in reduced vaccine effectiveness in all age groups during the 2014-2015 influenza season. In children, inactivated influenza vaccine (IIV) elicited neutralizing antibodies (Abs) against drifted strains at significantly lower levels than against the vaccine strain. Little is known about the cross-reactivity of cell-mediated immunity against drifted strains in children.

Methods

Children aged 3-17 years (n = 48) received IIV during the 2014-2015 influenza season. Peripheral blood mononuclear cells, collected before (on day 0) and after (on days 7 and 21) vaccination were evaluated for induction of cross-reactive plasmablasts, memory B cells, and cytokine-secreting CD4(+) and CD8(+) T cells against the vaccine and drifted A(H3N2) viruses by an enzyme-linked immunospot assay and flow cytometry.

Results

IIV increased frequencies of plasmablasts and memory B cells. The overall induction of the T-cell response was not significant. Both B-cell and T-cell responses showed significant cross-reactivity against A(H3N2) viruses. Age and preexisting immunity affected virus-specific plasmablast responses and fold-change of T-cell responses, respectively. The proportion of T-helper type 1-prone (ie, interferon ?- or tumor necrosis factor ?-secreting) CD4(+) T cell responses also increased with age.

Conclusions

In children aged 3-17 years, B- and T-cell responses following IIV receipt showed significant cross-reactivity against A(H3N2) viruses during a vaccine mismatch season.

SUBMITTER: Kim JH

PROVIDER: S-EPMC5021236 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Publications

Cell-Mediated Immunity Against Antigenically Drifted Influenza A(H3N2) Viruses in Children During a Vaccine Mismatch Season.

Kim Jin Hyang JH Mishina Margarita M Chung Jessie R JR Cole Kelly Stefano KS Nowalk Mary Patricia MP Martin Judith M JM Spencer Sarah S Flannery Brendan B Zimmerman Richard K RK Sambhara Suryaprakash S

The Journal of infectious diseases 20160817 7

<h4>Background</h4>Emergence of antigenically drifted influenza A(H3N2) viruses resulted in reduced vaccine effectiveness in all age groups during the 2014-2015 influenza season. In children, inactivated influenza vaccine (IIV) elicited neutralizing antibodies (Abs) against drifted strains at significantly lower levels than against the vaccine strain. Little is known about the cross-reactivity of cell-mediated immunity against drifted strains in children.<h4>Methods</h4>Children aged 3-17 years ...[more]

PMID: 27534687

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Project description:Current influenza vaccines do not provide effective protection against heterologous influenza viruses. The ability of the novel M2SR influenza vaccine to protect against drifted influenza viruses was evaluated in naïve ferrets and in ferrets with pre-existing immunity to influenza. In naïve ferrets, M2SR provided similar protection against drifted challenge viruses as the comparator vaccine, FluMist®. However, in ferrets with pre-existing immunity, M2SR provided superior protection than FluMist in two model systems. In the first model, ferrets were infected with influenza A H1N1pdm and influenza B viruses to mimic the diverse influenza exposure in humans. The pre-infected ferrets, seropositive to H1N1pdm and influenza B but seronegative to H3N2, were then vaccinated with H3N2 M2SR or monovalent H3N2 FluMist virus (A/Brisbane/10/2007, clade 1) and challenged 6?weeks later with a drifted H3N2 virus (clade 3C.2a). Antibody titers to Brisbane/10/2007 were higher in M2SR vaccinated ferrets than in FluMist vaccinated ferrets in the pre-infected ferrets whereas the opposite was observed in naïve ferrets. After challenge with drifted H3N2 virus, M2SR provided superior protection than FluMist monovalent vaccine. In the second model, the impact of homologous pre-existing immunity upon vaccine-induced protection was evaluated. Ferrets, pre-infected with H1N1pdm virus, were vaccinated 90?days later with H1N1pdm M2SR or FluMist monovalent vaccine and challenged 6?weeks later with a pre-pandemic seasonal H1N1 virus, A/Brisbane/59/2007 (Bris59). While cross-reactive serum IgG antibodies against the Bris59 HA were detected after vaccination, anti-Bris59 hemagglutination inhibition antibodies were only detected post-challenge. M2SR provided better protection against Bris59 challenge than FluMist suggesting that homologous pre-existing immunity affected FluMist virus to a greater degree than M2SR. These results suggest that the single replication intranasal M2SR vaccine provides effective protection against drifted influenza A viruses not only in naïve ferrets but also in those with pre-existing immunity in contrast to FluMist viruses.

Dataset Information

Cell-Mediated Immunity Against Antigenically Drifted Influenza A(H3N2) Viruses in Children During a Vaccine Mismatch Season.

Background

Methods

Results

Conclusions

Publications

Cell-Mediated Immunity Against Antigenically Drifted Influenza A(H3N2) Viruses in Children During a Vaccine Mismatch Season.

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