TY - JOUR
T1 - Magnitude and breadth of antibody cross-reactivity induced by recombinant influenza hemagglutinin trimer vaccine is enhanced by combination adjuvants
AU - Hernandez-Davies, Jenny E.
AU - Dollinger, Emmanuel P.
AU - Pone, Egest J.
AU - Felgner, Jiin
AU - Liang, Li
AU - Strohmeier, Shirin
AU - Jan, Sharon
AU - Albin, Tyler J.
AU - Jain, Aarti
AU - Nakajima, Rie
AU - Jasinskas, Algimantas
AU - Krammer, Florian
AU - Esser-Kahn, Aaron
AU - Felgner, Philip L.
AU - Nie, Qing
AU - Davies, D. Huw
N1 - Funding Information:
We thank Quy Nguyen and Melanie Oakes, UCI Genomics High Throughput Facility, for single cell transcriptomic sequencing. We also thank the UCI Laser Spectroscopy Labs for use of dynamic light scattering facilities. Supported by Defense Threat Reduction Agency (DTRA) Grant HDTRA1-18-1-0036 and NIH U01 Grant AI160397. ED and QN were supported by the NSF Grant DMS1763272 and a grant from Simons Foundation (594598). ED is also supported by the NIH Grant T32GM136624. Work in the Krammer laboratory was supported by NIAID Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051. The views expressed in this article are those of the authors and do not reflect the official policy or position of the U.S. Department of Defense or the U.S. Army.
Funding Information:
We thank Quy Nguyen and Melanie Oakes, UCI Genomics High Throughput Facility, for single cell transcriptomic sequencing. We also thank the UCI Laser Spectroscopy Labs for use of dynamic light scattering facilities. Supported by Defense Threat Reduction Agency (DTRA) Grant HDTRA1-18-1-0036 and NIH U01 Grant AI160397. ED and QN were supported by the NSF Grant DMS1763272 and a grant from Simons Foundation (594598). ED is also supported by the NIH Grant T32GM136624. Work in the Krammer laboratory was supported by NIAID Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051. The views expressed in this article are those of the authors and do not reflect the official policy or position of the U.S. Department of Defense or the U.S. Army.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85131120296&partnerID=8YFLogxK
U2 - 10.1038/s41598-022-12727-y
DO - 10.1038/s41598-022-12727-y
M3 - Article
C2 - 35654904
AN - SCOPUS:85131120296
SN - 2045-2322
VL - 12
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 9198
ER -