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Pandemic influenza virus vaccines boost hemagglutinin stalk-specific antibody responses in primed adult and pediatric cohorts
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Pandemic influenza virus vaccines boost hemagglutinin stalk-specific antibody responses in primed adult and pediatric cohorts
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Journal Article
Pandemic influenza virus vaccines boost hemagglutinin stalk-specific antibody responses in primed adult and pediatric cohorts
2019
Overview
Licensed influenza virus vaccines target the head domain of the hemagglutinin (HA) glycoprotein which undergoes constant antigenic drift. The highly conserved HA stalk domain is an attractive target to increase immunologic breadth required for universal influenza virus vaccines. We tested the hypothesis that immunization with a pandemic influenza virus vaccine boosts pre-existing anti-stalk antibodies. We used chimeric cH6/1, full length H2 and H18 HA antigens in an ELISA to measure anti-stalk antibodies in recipients participating in clinical trials of A/H1N1, A/H5N1 and A/H9N2 vaccines. The vaccines induced high titers of anti-H1 stalk antibodies in adults and children, with higher titers elicited by AS03-adjuvanted vaccines. We also observed cross-reactivity to H2 and H18 HAs. The A/H9N2 vaccine elicited plasmablast and memory B-cell responses. Post-vaccination serum from vaccinees protected mice against lethal challenge with cH6/1N5 and cH5/3N4 viruses. These findings support the concept of a chimeric HA stalk-based universal influenza virus vaccine. clinicaltrials.gov: NCT02415842.
Influenza vaccine: boosting immunity to hemagglutinin stalk domains
The head domain of influenza virus hemagglutinin (HA), the main target of licensed influenza virus vaccines, undergoes constant antigenic drift. The HA stalk domain, on the other hand, is highly conserved and is thus an attractive target for developing universal influenza vaccine formulations. Raffael Nachbagauer and colleagues now show that vaccination with pandemic influenza virus vaccines boosts pre-existing antibody responses to HA stalk domains in pediatric cohorts. Analysis of serum from individuals immunized with pandemic vaccines A/H1N1, A/H5N1 and A/H9N2, revealed basal levels of anti-stalk antibodies that were increased following immunization. The elicited antibodies had neutralization properties, and plasmablast responses from peripheral blood immune cells recovered from vaccinated individuals were also recorded. These findings support pandemic vaccines as a potential strategy towards universal influenza virus vaccines by expanding pre-existing antibodies against conserved HA stalk structures.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
