Inactivated rabies-vectored SARS-CoV-2 vaccine provides long-term immune response unaffected by vector immunity

Abstract

The objective of this study is to further analyze recombinant rabies virus-vectored SARS-CoV-2 vaccine, CORAVAX, as an effective COVID-19 vaccine strategy. CORAVAX has proven immunogenic and protective against SARS-CoV-2 in animal models. Here, we have screened adjuvants for the highest quality antibody titers, negated the concern of pre-existing rabies-vector immunity, and established its potential as a long-term COVID-19 vaccine. We have tested toll-like receptor 4 (TLR4) agonists, inflammasome activators, and alum adjuvants in CORAVAX and found TLR4-activating MPLA-AddaVax to have the greatest potential. We followed the humoral immune response to CORAVAX in mice with pre-existing rabies virus immunity and saw no significant differences compared to naive mice. We then followed the immune response to CORAVAX over several months and 1-year post-immunization. Mice maintained high antigen-specific serum antibody titers as well as long-lived antibody-secreting cells in the spleen and bone marrow. We believe this rabies-vector strategy combats the problem of waning immunity of other COVID-19 vaccines. These results together support CORAVAX’s potential during the ongoing COVID-19 pandemic.

Effects of adjuvants in a rabies-vectored Ebola virus vaccine on protection from surrogate challenge

“…RABV vaccination often protects long-term, and revaccination is rarely needed even after decades of previous immunization. We have shown that the RABV platform elicits long-term immunity to the foreign inserted antigen in a recombinant SARS-CoV-2 vaccine in mice 23 , and FILORAB1 has demonstrated durability of antibody responses in NHPs to 1 year 24 .…”

Long‐term immune response to Omicron‐specific mRNA vaccination in mice, hamsters, and nonhuman primates

“…These results indicated that splenic lymphocytes in animals after a long time from full vaccination can be rapidly recalled to an activated state when encountering the same antigens. Deeply, the results also reflected that draining LNs may play an important role in the early stage after mRNA vaccine immunization, while the long‐term rapid immune responses could be more dependent on the spleen 37,38 . Interestingly, the results also showed that a lower activation of B and T lymphocytes in mice vaccinated with the highest dose.…”

Effects of adjuvants on protection in a rabies-vectored Ebola virus vaccine

“…The inactivated RABV vaccine has been safely administered to millions of people, and our inactivated RABV-vectored vaccines have completed or are beginning clinical trials for COVID-19 and Lassa Fever, respectively. We have long-term immunogenicity data for the RABV vaccine platform at 1 year for SARS-CoV-2 in mice (in press), 20 and for Ebola, Sudan, Marburg, and Lassa fever virus in NHPs. 21 By network meta-analysis of all EBOV vaccines in humans, rVSV-ZEBOV exhibited the most risk-benefit, followed by the rAd5.ZEBOV-GP and ChAd3-EBO-Z vaccines.…”

“…19 RABV vaccination often protects long-term, and revaccination is rarely needed even after decades of previous immunization. We have shown that the RABV platform elicits long-term immunity to the foreign inserted antigen in a recombinant SARS-CoV-2 vaccine in mice (in press), 20 and FILORAB1 has demonstrated durability of antibody responses in NHPs to 1 year. 21 The ability of adjuvants to affect vaccine immune responses is an important consideration in vaccine development, especially for inactivated vaccine platforms.…”