A successful vaccine requires an antigen, an adjuvant, and a delivery strategy. Viral nanoparticles (VNPs) and virus-like particles (VLPs) are known to be potent adjuvants and here we utilize cowpea mosaic virus (CPMV) and bacteriophage Qβ as a vaccination platform technology. The VNPs are engineered to display the target antigen; moreover, the VLPs are then subjected to hot-melt extrusion to formulate slow-release VLP/PLGA formulations. We highlight the utility of this plug-and-play approach for development of vaccines targeting cardiovascular diseases (CVD) and infectious diseases such as HPV and COVID-19. For CVD we designed a trivalent vaccine displaying atherosclerosis-related B cell epitopes as antigens to block different checkpoint proteins in cholesterol metabolism (PCSK9, ApoB, and CETP). For HPV, an epitope derived from the highly conserved L2 capsid protein was used as antigen to develop a Qβ-based universal vaccine able to neutralize most HPV serotypes. And for COVID-19 we formulated trivalent COVID-19 vaccine candidates using Qβ and CPMV nanoparticles displaying SARS-CoV-2 S protein B cell epitopes. In each case efficacy of the VLP-based vaccine candidates is demonstrated, i.e. the trivalent CVD vaccines were immunogenic against PCSK9, ApoB, and CETP and lowered the cholesterol levels in plasma from vaccinated mice. And the HPV and COVID-19 vaccine candidates elicited antibodies neutralizing the target pathogen. In each case, the slow-release formulation demonstrated efficacy after single-dose administration. This multivalent vaccination approach combined with the novel implant-based delivery technology could be an excellent platform targeting various diseases, especially where the cold-chain and high costs are prohibitive for therapeutic biologics.

Single-dose, implant-based, viral nanoparticles vaccines: From cardiovascular to infectious diseases

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.