Magnitude and breadth of antibody cross-reactivity induced by recombinant influenza hemagglutinin trimer vaccine is enhanced by combination adjuvants.

Autor: Hernandez-Davies JE; Vaccine Research and Development Center, Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA, 92697, USA., Dollinger EP; Department of Mathematics, University of California, Irvine, CA, 92697, USA., Pone EJ; Vaccine Research and Development Center, Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA, 92697, USA., Felgner J; Vaccine Research and Development Center, Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA, 92697, USA., Liang L; Vaccine Research and Development Center, Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA, 92697, USA., Strohmeier S; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Jan S; Vaccine Research and Development Center, Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA, 92697, USA., Albin TJ; Department of Chemistry, University of California, Irvine, CA, 92697, USA.; Avidity Biosciences, San Diego, CA, 92121, USA., Jain A; Vaccine Research and Development Center, Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA, 92697, USA., Nakajima R; Vaccine Research and Development Center, Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA, 92697, USA., Jasinskas A; Vaccine Research and Development Center, Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA, 92697, USA., Krammer F; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Esser-Kahn A; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, 60637, USA., Felgner PL; Vaccine Research and Development Center, Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA, 92697, USA., Nie Q; Department of Mathematics, University of California, Irvine, CA, 92697, USA., Davies DH; Vaccine Research and Development Center, Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA, 92697, USA. ddavies@uci.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 Jun 02; Vol. 12 (1), pp. 9198. Date of Electronic Publication: 2022 Jun 02.
DOI: 10.1038/s41598-022-12727-y
Abstrakt: 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. The Author(s).)
Databáze: MEDLINE
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