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

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 Stephensonf*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

211 Citations (Scopus)

Abstract

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 crossreactive neutralizing antibodies rapidly. These results suggest that pre-pandemic vaccination strategies should be considered.

Original languageEnglish
Pages (from-to)7962-7967
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number19
DOIs
Publication statusPublished - 12 May 2009

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