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Title: Fast rise of broadly cross-reactive antibodies after boosting long-lived human memory B cells primed by an MF59 adjuvanted prepandemic vaccine
Authors: Galli, Grazia
Hancock, Kathy
Hoschler, Katja
DeVos, Joshua
Praus, Michaela
Bardelli, Monia
Malzone, Carmine
Castellino, Flora
Gentile, Chiara
McNally, Teresa
Del Giudice, Guiseppe
Banzhoff, Angelika
Brauer, Volker
Montomoli, Emanuele
Zambon, Maria C.
Katz, Jacqueline M.
Nicholson, Karl G.
Stephenson, Iain
First Published: 12-May-2009
Publisher: National Academy of Sciences of the United States of America
Citation: Proceedings of the National Academy of Sciences of the United States of America, 2009, 106 (19), pp. 7962-7967.
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 cross-reactive neutralizing antibodies rapidly. These results suggest that pre-pandemic vaccination strategies should be considered.
DOI Link: 10.1073/pnas.0903181106
ISSN: 1091-6490
Type: Article
Rights: This is the author's final draft of the paper published as Proceedings of the National Academy of Sciences of the United States of America, 2009, 106 (19), pp. 7962-7967. The final version is available from Doi: 10.1073/pnas.0903181106
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

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