Fast rise of broadly cross-reactive antibodies after boosting long-lived human memory B cells primed by an MF59 adjuvanted prepandemic vaccine

• DOI: 10.1073/pnas.0903181106
• Publication Date: 2009-04-28T01:50:52Z
• Authors: Grazia Galli; Kathy Hancock; Katja Hoschler; Joshua DeVos; Michaela Praus; Monia Bardelli; Carmine Malzone; Flora Castellino; Chiara Gentile; Teresa McNally; Giuseppe Del Giudice; Angelika Banzhoff; Volker Brauer; Emanuele Montomoli; Maria Zambon; Jacqueline Katz; Karl Nicholson; Iain Stephenson
• Keywords: Squalene; 0301 basic medicine; B-Lymphocytes; Vaccines; Influenza A Virus, H5N1 Subtype; Vaccination; Polysorbates; Models, Theoretical; 3. Good health; 03 medical and health sciences; Adjuvants, Immunologic; Influenza Vaccines; Neutralization Tests; Immunoglobulin G; Antibody Formation; Influenza, Human; Humans; Immunologic Memory

Proactive priming before the next pandemic could induce immune memory responses to novel influenza antigens. In an open-label study, we analyzed B cell memory and antibody responses of 54 adults who received 2 7.5-μg doses of MF59-adjuvanted A/Vietnam/1194/2004 clade 1 (H5N1) vaccine. Twenty-four subjects had been previously primed with MF59-adjuvanted or plain clade 0-like A/duck/Singapore/1997 (H5N3) vaccine during 1999–2001. The prevaccination frequency of circulating memory B cells reactive to A/Vietnam/1194/2004 was low in both primed and unprimed individuals. However, at day 21 after boosting, MF59-adjuvanted primed subjects displayed a higher frequency of H5N1-specific memory B cells than plain-primed or unprimed subjects. The immune memory was rapidly mobilized by a single vaccine administration and resulted in high titers of neutralizing antibodies to antigenically diverse clade 0, 1, and 2 H5N1 viruses already at day 7. In general, postvaccination antibody titers were significantly higher in primed subjects than in unprimed subjects. Subjects primed with MF59-adjuvanted vaccine responded significantly better than those primed with plain vaccine, most notably in early induction and duration of cross-reacting antibody responses. After 6 months, high titers of cross-reactive antibody remained detectable among MF59-primed subjects. We conclude that distant priming with clade 0-like H5N3 induces a pool of cross-reactive memory B cells that can be boosted rapidly years afterward by a mismatched MF59-adjuvanted vaccine to generate high titers of cross-reactive neutralizing antibodies rapidly. These results suggest that pre-pandemic vaccination strategies should be considered.