Pandemic influenza virus vaccines boost hemagglutinin stalk-specific antibody responses in primed adult and pediatric cohorts

Raffael Nachbagauer, Bruno Salaun, Daniel Stadlbauer, Mohammad A. Behzadi, Damien Friel, Arvind Rajabhathor, Angela Choi, Randy A. Albrecht, Muriel Debois, Adolfo García-Sastre, Ronan N. Rouxel, Weina Sun, Peter Palese, Corey P. Mallett, Bruce L. Innis, Florian Krammer, Carine Claeys

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

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.

Original languageEnglish
Article number51
Journalnpj Vaccines
Volume4
Issue number1
DOIs
StatePublished - 1 Dec 2019

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