Adenoviral-Based Vaccine Elicits Robust Systemic and Mucosal Cross-Reactive Responses in African Green Monkeys and Reduces Shedding after SARS-CoV-2 Challenge

Abstract

As new SARS-CoV-2 variants continue to emerge and impact communities worldwide, efforts to develop next generation vaccines that enhance mucosal immunity would be beneficial for protecting individuals and reducing community transmission. We have developed a non-replicating recombinant adenovirus vector (rAd5) vaccine delivered by mucosal administration engineered to express both a protein antigen and a novel molecular adjuvant in the same cell. Here we describe the immunogenicity of three unique SARS-CoV-2 rAd5 vaccine preclinical candidates and their efficacy following viral challenge in African green monkeys. Animals were prime and boost immunized intranasally twenty-nine days apart with rAd5 vaccine candidates containing viral SARS-CoV-2 spike protein alone or in combination with viral nucleocapsid. Mucosal immunization elicited significant increases in antigen-specific serum antibody responses and functional neutralizing activity against multiple variants of concern. Robust antigen specific mucosal IgA responses were observed after a single administration of rAd5 and generated strong cross-reactive neutralizing antibodies against multiple variants including delta. Importantly, all vaccinated animals exhibited a significant reduction in viral loads and infectious particle shedding in both the nasal passages and lower airways compared to unvaccinated controls following challenge with SARS-CoV-2. These findings demonstrate that mucosal immunization using rAd5 is highly immunogenic, confers protective cross-reactive humoral responses in both the circulation and mucosa, and reduces viral loads and shedding upon challenge with multiple SARS-CoV-2 variants.

Mucosal immunization with Ad5-based vaccines protects Syrian hamsters from challenge with omicron and delta variants of SARS-CoV-2

“…Another limitation is that each experiment was only performed once for both the omicron and delta cohorts, as the high cost of BSL-3 infections and the everevolving variants made an exact experimental repeat ill-favored. Although these challenge experiments were only performed once each, the observation that mucosal application of this rAd5-S is able to generate both serum and mucosal immune responses has been shown in other hamster studies (20,21), NHP studies (43,44), and studies from human clinical trials (22). Future experiments will be performed to further confirm our observations, and the data analyzed here will inform the experimental design of studies including those that utilize this mucosal rAd5-S vaccine to boost animals that have previously been immunized with mRNA vaccines in immunogenicity studies.…”