Nasal vaccination with an rVSV-ΔG-spike vaccine induces robust mucosal and systemic protective immunity against SARS-CoV-2 variants of concern

The emergence of rapidly spreading variants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) poses a major challenge to the protective efficacy of vaccines and therapeutic antibodies. These variants contain mutations at specific amino acids that impede vaccines and antibodies efficacy. Hence, current intramuscular injected vaccines fail to induce sufficient mucosal immunity at the site of infection. BriLife^® (rVSV-ΔG-spike) is a SARS-CoV-2 vaccine candidate based on a replication-competent vesicular stomatitis virus (VSV) platform, presenting membrane-associated modified spike structures. BriLife^® recently completed phase II clinical trial. We asked whether the mucosal distribution of hACE2 receptor can be utilized by BriLife^® to achieve preferred mucosal and systemic immunity. We therefore compared the protection afforded by intranasal administration of the vaccine to the conventional intramuscular route in K18 hACE2 transgenic mice and golden Syrian hamsters. Both vaccination routes induced systemic immunity and conferred protection from death or disease. Yet, intranasal administration was found to be superior over intramuscular administration by: A) inducing binding and neutralizing IgA and IgG antibodies, B) inducing mucosal T cell immunity, C) enabling reduction of vaccine dose, D) significantly reducing viral load at the nasal turbinates early post-infection, and E) preventing virus spread to co-caged animals.

Taken together, intranasal vaccination with BriLife^® induces efficient immunity at the respiratory system that may prove advantageous over intramuscular vaccines against future SARS-CoV-2 VOCs.