Lecture Series: Two-dose regimen sequential immunization of COVID-19 protein vaccines provided early and long protection

Monday, May 23 2022 - 11:00am to 12:00pm

Background: Despite COVID-19 mRNA vaccines were approved, the stringent temperature requirement may limit their application, especially in underdeveloped countries. Other platforms of vaccine are needed to meet huge global demands to quell this pandemic. Methods: we conjugated multiple trimeric spike (Wuhan strain with D614G mutation) ectodomain subunits onto Ferritin nanoparticle to generate protein vaccine candidate, REVC-128, and characterized antigenicity and immunogenicity of this candidate with comparison to trimeric spike without nanoparticle presentation. Results: In-vivo immunogenicity evaluation in mice indicated that a single dose of this vaccine induced potent serum neutralizing antibody titer at two weeks post immunization, which was significantly higher than titer induced by trimeric spike protein without nanoparticle presentation. The comparison of serum binding to spike subunits between animals immunized by spike with and without nanoparticle presentation indicated that nanoparticle preferred the display of spike RBD (Receptor-Binding Domain) over S2 subunit, likely resulting in a more neutralizing but less cross-reactive antibody response. Moreover, a Syrian golden hamster in-vivo model for SARS-CoV-2 virus challenge was implemented at two weeks post a single dose of REVC-128 immunization. The results showed that vaccination protected hamsters against SARS-CoV-2 virus challenge with evidence of steady body weight, suppressed viral loads and alleviation of tissue damage for protected animals, compared with ~10% weight loss, high viral loads and tissue damage in unprotected animals. Furthermore, the data showed that vaccine REVC-128 is thermostable at up to 37°C for at least 4 weeks and room temperature for 6 months. Besides single dose regimen, we found a two-dose regimen sequential immunization strategy with nanoparticle vaccine to prime and soluble trimeric spike to boost could maintain the optimal neutralizing antibody titer before and after the booster for an earlier and longer protection period. We also observed this sequential immunization provided increased serum neutralizing antibody activity against multiple variants of pseudoviruses, including Beta, Delta and Omicron, but much lower than WT strain. Conclusion: These findings, along with history of safety for protein vaccines, suggested that this sequential immunization strategy could provide unique solution against SARS-CoV-2 infection, other than mRNA or two doses of same nanoparticle (e.g., Novavax). A vaccine design to provide broad protection is necessary for the immune escape variants.