Fast rise of broadly cross-reactive antibodies after boosting long-lived human memory B cells primed by an MF59 adjuvanted prepandemic vaccine.
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-microg 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.
Translational Medicine, Novartis Vaccines, Siena, Italy 53100.
Grazia
G
Galli
Kathy
K
Hancock
Katja
K
Hoschler
Joshua
J
DeVos
Michaela
M
Praus
Monia
M
Bardelli
Carmine
C
Malzone
Flora
F
Castellino
Chiara
C
Gentile
Teresa
T
McNally
Giuseppe
G
Del Giudice
Angelika
A
Banzhoff
Volker
V
Brauer
Emanuele
E
Montomoli
Maria
M
Zambon
Jacqueline
J
Katz
Karl
K
Nicholson
Iain
I
Stephenson
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D007156:Immunologic Memory / Q000187:drug effects*; D053124:Influenza A Virus, H5N1 Subtype / Q000378:metabolism; D007252:Influenza Vaccines / Q000737:chemistry; D007251:Influenza, Human / Q000517:prevention & control; D008962:Models, Theoretical; D009500:Neutralization Tests; D011136:Polysorbates / Q000494:pharmacology*; D013185:Squalene / Q000494:pharmacology*; D014611:Vaccination; D014612:Vaccines / Q000276:immunology
D000276:Adjuvants, Immunologic; D007074:Immunoglobulin G; D007252:Influenza Vaccines; C089950:MF59 oil emulsion; D011136:Polysorbates; D014612:Vaccines; D013185:Squalene