tetano
Editor, Senior Moderator
J Clin Invest. 2019 Dec 17. pii: 129520. doi: 10.1172/JCI129520. [Epub ahead of print] [h=1]Selective induction of antibody effector functional responses using MF59-adjuvanted vaccination.[/h]
Boudreau CM[SUP]1,[/SUP][SUP]2[/SUP], Yu WH[SUP]1[/SUP], Suscovich TJ[SUP]1[/SUP], Talbot HK[SUP]3,[/SUP][SUP]4[/SUP], Edwards KM[SUP]5[/SUP], Alter G[SUP]1[/SUP].
[h=3]Author information[/h] 1 Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA. 2 PhD program in Virology, Division of Medical Sciences, Harvard University, Boston, Massachusetts, USA. 3 Department of Medicine. 4 Department of Health Policy, and. 5 Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
[h=3]Abstract[/h] Seasonal and pandemic influenza infection remains a major public health concern worldwide. Driving robust humoral immunity has been a challenge given preexisting, often cross-reactive, immunity and in particular, poorly immunogenic avian antigens. To overcome immune barriers, the adjuvant MF59 has been used in seasonal influenza vaccines to increase antibody titers and improve neutralizing activity, translating to a moderate increase in protection in vulnerable populations. However, its effects on stimulating antibody effector functions, including NK cell activation, monocyte phagocytosis, and complement activity, all of which have been implicated in protection against influenza, have yet to be defined. Using systems serology, we assessed changes in antibody functional profiles in individuals who received H5N1 avian influenza vaccine administered with MF59, with alum, or delivered unadjuvanted. MF59 elicited antibody responses that stimulated robust neutrophil phagocytosis and complement activity. Conversely, vaccination with MF59 recruited NK cells poorly and drove moderate monocyte phagocytic activity, both likely compromised because of the induction of antibodies that did not bind FCGR3A. Collectively, defining the humoral antibody functions induced by distinct adjuvants may provide a path to designing next-generation vaccines that can selectively leverage the humoral immune functions, beyond binding and neutralization, resulting in better protection from infection.
[h=4]KEYWORDS:[/h] Adaptive immunity; Immunology; Influenza; Innate immunity; Vaccines
PMID: 31845904 DOI: 10.1172/JCI129520
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Boudreau CM[SUP]1,[/SUP][SUP]2[/SUP], Yu WH[SUP]1[/SUP], Suscovich TJ[SUP]1[/SUP], Talbot HK[SUP]3,[/SUP][SUP]4[/SUP], Edwards KM[SUP]5[/SUP], Alter G[SUP]1[/SUP].
[h=3]Author information[/h] 1 Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA. 2 PhD program in Virology, Division of Medical Sciences, Harvard University, Boston, Massachusetts, USA. 3 Department of Medicine. 4 Department of Health Policy, and. 5 Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
[h=3]Abstract[/h] Seasonal and pandemic influenza infection remains a major public health concern worldwide. Driving robust humoral immunity has been a challenge given preexisting, often cross-reactive, immunity and in particular, poorly immunogenic avian antigens. To overcome immune barriers, the adjuvant MF59 has been used in seasonal influenza vaccines to increase antibody titers and improve neutralizing activity, translating to a moderate increase in protection in vulnerable populations. However, its effects on stimulating antibody effector functions, including NK cell activation, monocyte phagocytosis, and complement activity, all of which have been implicated in protection against influenza, have yet to be defined. Using systems serology, we assessed changes in antibody functional profiles in individuals who received H5N1 avian influenza vaccine administered with MF59, with alum, or delivered unadjuvanted. MF59 elicited antibody responses that stimulated robust neutrophil phagocytosis and complement activity. Conversely, vaccination with MF59 recruited NK cells poorly and drove moderate monocyte phagocytic activity, both likely compromised because of the induction of antibodies that did not bind FCGR3A. Collectively, defining the humoral antibody functions induced by distinct adjuvants may provide a path to designing next-generation vaccines that can selectively leverage the humoral immune functions, beyond binding and neutralization, resulting in better protection from infection.
[h=4]KEYWORDS:[/h] Adaptive immunity; Immunology; Influenza; Innate immunity; Vaccines
PMID: 31845904 DOI: 10.1172/JCI129520
Free full text