This is a summary, written by members of the CITF Secretariat, of:
Parham KA, Kim GN, Richer CG, Ninkov M, Wu K, Saeedian N, Li Y, Rashu R, Barr SD, Arts EJ, Haeryfar SMM, Kang CY, Troyer RM. Monovalent and trivalent VSV-based COVID-19 vaccines elicit neutralizing antibodies and CD8+ T cells against SARS-CoV-2 variants. iScience. 2023 Apr 21;26(4):106292. doi: https://doi.org/10.1016/j.isci.2023.106292.
The results and/or conclusions contained in the research do not necessarily reflect the views of all CITF members.
A CITF-funded study, published in iScience, developed four spike-based vaccines against the SARS-CoV-2 virus and measured antibody and cellular responses. All four – one based on the wildtype (original strain), one based on Beta, one based on Delta and a trivalent vaccine combining all three – produced a strong neutralizing antibody response in an animal model against all SARS-CoV-2 variants, including against the Omicron variant. The study was led by Dr. Ryan Troyer (Western University).
A recombinant vesicular stomatitis virus (rVSV) platform was used to generate the vaccines. After mice were prime-boost immunized with various combinations of 3 monovalent variant vaccines and the trivalent vaccine, sera were analysed to measure antibody and cellular immunity.
- A prime-vaccination (first dose) with the trivalent vaccine, followed by a booster of the same trivalent vaccine (trivalent/trivalent regimen), consistently produced a neutralizing antibody response against all SARS-CoV-2 variants tested, with all mice generating neutralizing antibodies.
- The trivalent/trivalent regimen was the most effective, with a 10.9-fold increase in neutralization capacity against the Delta variant compared to the wildtype/wildtype regimen.
- For Omicron, the most highly mutated variant to date, a first dose and booster dose with the Delta/Delta vaccine was the most effective regimen (1.9-fold increase in neutralizing titers), followed by the trivalent/trivalent regimen (1.5-fold). The wildtype/wildtype vaccine regimen was equally as effective as the wildtype/Delta vaccine regimen in neutralizing the virus (1.0- and 0.8-fold, respectively).
- All vaccines induced a spike-specific CD8+T cell response to SARS-CoV-2.
- The greatest CD8+ T cell response was seen in the wildtype/wildtype and Trivalent/Trivalent immunized mice compared to the Beta/Beta, Delta/Delta, and wildtype/Delta immunized mice.
The study shows that rVSV is an effective platform for the generation of SARS-CoV-2 vaccines against variants of the original virus. VSV does not commonly infect humans and provides a safe vaccine platform that effectively induces mucosal and systemic immunity while having several manufacturing advantages.