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Inclusion of cGAMP within virus‐like particle vaccines enhances their immunogenicity
Author(s) -
Chauveau Lise,
Bridgeman Anne,
Tan Tiong K,
Beveridge Ryan,
Frost Joe N,
Rijal Pramila,
PedrozaPacheco Isabela,
Partridge Thomas,
GilbertJaramillo Javier,
Knight Michael L,
Liu Xu,
Russell Rebecca A,
Borrow Persephone,
Drakesmith Hal,
Townsend Alain R,
Rehwinkel Jan
Publication year - 2021
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.202152447
Subject(s) - immunogenicity , virus like particle , vesicular stomatitis virus , virus , virology , biology , viral envelope , adjuvant , rhabdoviridae , antibody , glycoprotein , antigen , vaccination , microbiology and biotechnology , recombinant dna , immunology , biochemistry , gene
Cyclic GMP‐AMP (cGAMP) is an immunostimulatory molecule produced by cGAS that activates STING. cGAMP is an adjuvant when administered alongside antigens. cGAMP is also incorporated into enveloped virus particles during budding. Here, we investigate whether inclusion of cGAMP within viral vaccine vectors enhances their immunogenicity. We immunise mice with virus‐like particles (VLPs) containing HIV‐1 Gag and the vesicular stomatitis virus envelope glycoprotein G (VSV‐G). cGAMP loading of VLPs augments CD4 and CD8 T‐cell responses. It also increases VLP‐ and VSV‐G‐specific antibody titres in a STING‐dependent manner and enhances virus neutralisation, accompanied by increased numbers of T follicular helper cells. Vaccination with cGAMP‐loaded VLPs containing haemagglutinin induces high titres of influenza A virus neutralising antibodies and confers protection upon virus challenge. This requires cGAMP inclusion within VLPs and is achieved at markedly reduced cGAMP doses. Similarly, cGAMP loading of VLPs containing the SARS‐CoV‐2 Spike protein enhances Spike‐specific antibody titres. cGAMP‐loaded VLPs are thus an attractive platform for vaccination.