cGAMP loading enhances the immunogenicity of VLP vaccines [article]

Lise Chauveau, Anne Bridgeman, Tiong Kit Tan, Ryan Beveridge, Joe Frost, Isabela Pedroza-Pacheco, Thomas Partridge, Persephone Borrow, Hal Drakesmith, Alain Townsend, Jan Rehwinkel
2020 bioRxiv   pre-print
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
more » ... hin 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.
doi:10.1101/2020.01.03.893586 fatcat:i3knuis4uzdghp7u47r326ejwe