PT  - JOURNAL ARTICLE
AU  - Lise Chauveau
AU  - Anne Bridgeman
AU  - Tiong Kit Tan
AU  - Ryan Beveridge
AU  - Joe Frost
AU  - Isabela Pedroza-Pacheco
AU  - Thomas Partridge
AU  - Persephone Borrow
AU  - Hal Drakesmith
AU  - Alain Townsend
AU  - Jan Rehwinkel
TI  - cGAMP loading enhances the immunogenicity of VLP vaccines
AID  - 10.1101/2020.01.03.893586
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.01.03.893586
4099  - http://biorxiv.org/content/early/2020/01/03/2020.01.03.893586.short
4100  - http://biorxiv.org/content/early/2020/01/03/2020.01.03.893586.full
AB  - Cyclic GMP-AMP (cGAMP) is an immunostimulatory second messenger produced by cGAS that activates STING. Soluble cGAMP acts as an adjuvant when administered with antigens. cGAMP is also incorporated into enveloped virus particles during budding. We hypothesised that inclusion of the adjuvant cGAMP within viral vaccine vectors would promote adaptive immunity against vector antigens. We immunised mice with virus-like particles (VLPs) containing the HIV-1 Gag protein and VSV-G. Inclusion of cGAMP within these VLPs augmented splenic VLP-specific CD4 and CD8 T cell responses. It also increased VLP- and VSV-G-specific serum antibody titres and enhanced in vitro virus neutralisation. The superior antibody response was accompanied by increased numbers of T follicular helper cells in draining lymph nodes. Vaccination with cGAMP-loaded VLPs containing haemagglutinin induced high titres of influenza A virus neutralising antibodies and conferred protection following subsequent influenza A virus challenge. Together, these results show that incorporating cGAMP into VLPs enhances their immunogenicity, making cGAMP-VLPs an attractive platform for novel vaccination strategies.Short summary cGAMP is an innate immune signalling molecule that can be transmitted between cells by inclusion in enveloped virions. This study demonstrates enhanced immunogenicity of HIV-derived virus-like particles containing cGAMP. Viral vectors loaded with cGAMP may thus be potent vaccines.