tetano
Editor, Senior Moderator
Sci Rep
. 2022 Jun 2;12(1):9198.
doi: 10.1038/s41598-022-12727-y.
Magnitude and breadth of antibody cross-reactivity induced by recombinant influenza hemagglutinin trimer vaccine is enhanced by combination adjuvants
Jenny E Hernandez-Davies[SUP] 1 [/SUP], Emmanuel P Dollinger[SUP] 2 [/SUP], Egest J Pone[SUP] 1 [/SUP], Jiin Felgner[SUP] 1 [/SUP], Li Liang[SUP] 1 [/SUP], Shirin Strohmeier[SUP] 3 [/SUP], Sharon Jan[SUP] 1 [/SUP], Tyler J Albin[SUP] 4 5 [/SUP], Aarti Jain[SUP] 1 [/SUP], Rie Nakajima[SUP] 1 [/SUP], Algimantas Jasinskas[SUP] 1 [/SUP], Florian Krammer[SUP] 3 6 [/SUP], Aaron Esser-Kahn[SUP] 7 [/SUP], Philip L Felgner[SUP] 1 [/SUP], Qing Nie[SUP] 2 [/SUP], D Huw Davies[SUP] 8 [/SUP]
Affiliations
Abstract
The effects of adjuvants for increasing the immunogenicity of influenza vaccines are well known. However, the effect of adjuvants on increasing the breadth of cross-reactivity is less well understood. In this study we have performed a systematic screen of different toll-like receptor (TLR) agonists, with and without a squalene-in-water emulsion on the immunogenicity of a recombinant trimerized hemagglutinin (HA) vaccine in mice after single-dose administration. Antibody (Ab) cross-reactivity for other variants within and outside the immunizing subtype (homosubtypic and heterosubtypic cross-reactivity, respectively) was assessed using a protein microarray approach. Most adjuvants induced broad IgG profiles, although the response to a combination of CpG, MPLA and AddaVax (termed 'IVAX-1') appeared more quickly and reached a greater magnitude than the other formulations tested. Antigen-specific plasma cell labeling experiments show the components of IVAX-1 are synergistic. This adjuvant preferentially stimulates CD4 T cells to produce Th1>Th2 type (IgG2c>IgG1) antibodies and cytokine responses. Moreover, IVAX-1 induces identical homo- and heterosubtypic IgG and IgA cross-reactivity profiles when administered intranasally. Consistent with these observations, a single-cell transcriptomics analysis demonstrated significant increases in expression of IgG1, IgG2b and IgG2c genes of B cells in H5/IVAX-1 immunized mice relative to naïve mice, as well as significant increases in expression of the IFNγ gene of both CD4 and CD8 T cells. These data support the use of adjuvants for enhancing the breath and durability of antibody responses of influenza virus vaccines.
. 2022 Jun 2;12(1):9198.
doi: 10.1038/s41598-022-12727-y.
Magnitude and breadth of antibody cross-reactivity induced by recombinant influenza hemagglutinin trimer vaccine is enhanced by combination adjuvants
Jenny E Hernandez-Davies[SUP] 1 [/SUP], Emmanuel P Dollinger[SUP] 2 [/SUP], Egest J Pone[SUP] 1 [/SUP], Jiin Felgner[SUP] 1 [/SUP], Li Liang[SUP] 1 [/SUP], Shirin Strohmeier[SUP] 3 [/SUP], Sharon Jan[SUP] 1 [/SUP], Tyler J Albin[SUP] 4 5 [/SUP], Aarti Jain[SUP] 1 [/SUP], Rie Nakajima[SUP] 1 [/SUP], Algimantas Jasinskas[SUP] 1 [/SUP], Florian Krammer[SUP] 3 6 [/SUP], Aaron Esser-Kahn[SUP] 7 [/SUP], Philip L Felgner[SUP] 1 [/SUP], Qing Nie[SUP] 2 [/SUP], D Huw Davies[SUP] 8 [/SUP]
Affiliations
- PMID: 35654904
- DOI: 10.1038/s41598-022-12727-y
Abstract
The effects of adjuvants for increasing the immunogenicity of influenza vaccines are well known. However, the effect of adjuvants on increasing the breadth of cross-reactivity is less well understood. In this study we have performed a systematic screen of different toll-like receptor (TLR) agonists, with and without a squalene-in-water emulsion on the immunogenicity of a recombinant trimerized hemagglutinin (HA) vaccine in mice after single-dose administration. Antibody (Ab) cross-reactivity for other variants within and outside the immunizing subtype (homosubtypic and heterosubtypic cross-reactivity, respectively) was assessed using a protein microarray approach. Most adjuvants induced broad IgG profiles, although the response to a combination of CpG, MPLA and AddaVax (termed 'IVAX-1') appeared more quickly and reached a greater magnitude than the other formulations tested. Antigen-specific plasma cell labeling experiments show the components of IVAX-1 are synergistic. This adjuvant preferentially stimulates CD4 T cells to produce Th1>Th2 type (IgG2c>IgG1) antibodies and cytokine responses. Moreover, IVAX-1 induces identical homo- and heterosubtypic IgG and IgA cross-reactivity profiles when administered intranasally. Consistent with these observations, a single-cell transcriptomics analysis demonstrated significant increases in expression of IgG1, IgG2b and IgG2c genes of B cells in H5/IVAX-1 immunized mice relative to naïve mice, as well as significant increases in expression of the IFNγ gene of both CD4 and CD8 T cells. These data support the use of adjuvants for enhancing the breath and durability of antibody responses of influenza virus vaccines.