tetano
Editor, Senior Moderator
J Virol. 2016 May 25. pii: JVI.00339-16. [Epub ahead of print]
[h=1]MF59 adjuvant effects on inducing isotype-switched IgG antibodies and protection after immunization with T-dependent influenza virus vaccine in the absence of CD4+ T cells.[/h] Ko EJ[SUP]1[/SUP], Lee YT[SUP]2[/SUP], Kim KH[SUP]2[/SUP], Jung YJ[SUP]1[/SUP], Lee Y[SUP]1[/SUP], Denning TL[SUP]2[/SUP], Kang SM[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] CD4[SUP]+[/SUP] T cells play a central role in orchestrating adaptive immunity. To better understand the roles of CD4[SUP]+[/SUP] T cells in the adjuvant effects, we investigated the efficacy of T-dependent influenza virus split vaccine with MF59? or alum in CD4-knockout (CD4KO) and wild-type (WT) mice. CD4[SUP]+[/SUP] T cells were required for the induction of IgG antibody responses to split vaccine and alum adjuvant effects. In contrast, MF59? was found to be highly effective in raising isotype-switched IgG antibodies to T-dependent influenza split vaccine in CD4KO mice or CD4-depleted WT mice, equivalent to those in intact WT mice, thus overcoming the deficiency of CD4[SUP]+[/SUP] T cells in helping B cells and inducing immunity against influenza virus. MF59-adjuvanted influenza split vaccination was able to induce protective CD8[SUP]+[/SUP] T cells and long-lived antibody-secreting cells in CD4KO mice. MF59 adjuvant effects in CD4KO mice might be associated with uric acid, inflammatory cytokines, and recruitment of multiple immune cells at the injection site, but their cellularity and phenotypes were different from those in WT mice. These findings suggest a new paradigm of CD4-independent adjuvant mechanisms, providing the rationales to improve vaccine efficacy in infants, elderly, and immune-compromised patients as well as in healthy adults.
[h=4]IMPORTANCE:[/h] MF59-adjuvanted influenza vaccines were licensed for human vaccination, but the detailed mechanisms are not fully elucidated. CD4[SUP]+[/SUP] T cells are required to induce antibody isotype switching and long-term memory responses. In contrast, we discovered that MF59 was highly effective in inducing isotype-switched IgG antibodies and long-term protective immune responses to T-dependent influenza vaccine independent of CD4[SUP]+[/SUP] T cells. These findings are highly significant (1). MF59 can overcome a defect of CD4[SUP]+[/SUP] T cells in inducing protective immunity to T-dependent influenza split vaccination (2). A CD4-independent pathway can be an alternative mechanism for certain adjuvants such as MF59 (3). This study has significant implications for improving vaccine efficacies in young children, elderly, and immune-compromised populations.
Copyright ? 2016, American Society for Microbiology. All Rights Reserved.
PMID: 27226368 [PubMed - as supplied by publisher]
[h=1]MF59 adjuvant effects on inducing isotype-switched IgG antibodies and protection after immunization with T-dependent influenza virus vaccine in the absence of CD4+ T cells.[/h] Ko EJ[SUP]1[/SUP], Lee YT[SUP]2[/SUP], Kim KH[SUP]2[/SUP], Jung YJ[SUP]1[/SUP], Lee Y[SUP]1[/SUP], Denning TL[SUP]2[/SUP], Kang SM[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] CD4[SUP]+[/SUP] T cells play a central role in orchestrating adaptive immunity. To better understand the roles of CD4[SUP]+[/SUP] T cells in the adjuvant effects, we investigated the efficacy of T-dependent influenza virus split vaccine with MF59? or alum in CD4-knockout (CD4KO) and wild-type (WT) mice. CD4[SUP]+[/SUP] T cells were required for the induction of IgG antibody responses to split vaccine and alum adjuvant effects. In contrast, MF59? was found to be highly effective in raising isotype-switched IgG antibodies to T-dependent influenza split vaccine in CD4KO mice or CD4-depleted WT mice, equivalent to those in intact WT mice, thus overcoming the deficiency of CD4[SUP]+[/SUP] T cells in helping B cells and inducing immunity against influenza virus. MF59-adjuvanted influenza split vaccination was able to induce protective CD8[SUP]+[/SUP] T cells and long-lived antibody-secreting cells in CD4KO mice. MF59 adjuvant effects in CD4KO mice might be associated with uric acid, inflammatory cytokines, and recruitment of multiple immune cells at the injection site, but their cellularity and phenotypes were different from those in WT mice. These findings suggest a new paradigm of CD4-independent adjuvant mechanisms, providing the rationales to improve vaccine efficacy in infants, elderly, and immune-compromised patients as well as in healthy adults.
[h=4]IMPORTANCE:[/h] MF59-adjuvanted influenza vaccines were licensed for human vaccination, but the detailed mechanisms are not fully elucidated. CD4[SUP]+[/SUP] T cells are required to induce antibody isotype switching and long-term memory responses. In contrast, we discovered that MF59 was highly effective in inducing isotype-switched IgG antibodies and long-term protective immune responses to T-dependent influenza vaccine independent of CD4[SUP]+[/SUP] T cells. These findings are highly significant (1). MF59 can overcome a defect of CD4[SUP]+[/SUP] T cells in inducing protective immunity to T-dependent influenza split vaccination (2). A CD4-independent pathway can be an alternative mechanism for certain adjuvants such as MF59 (3). This study has significant implications for improving vaccine efficacies in young children, elderly, and immune-compromised populations.
Copyright ? 2016, American Society for Microbiology. All Rights Reserved.
PMID: 27226368 [PubMed - as supplied by publisher]