Intranasal administration of unadjuvanted SARS‐CoV‐2 spike antigen boosts antigen‐specific immune responses induced by parenteral protein subunit vaccine prime in mice and hamsters

Abstract

With the continued transmission of SARS‐CoV‐2 across widely vaccinated populations, it remains important to develop new vaccines and vaccination strategies capable of providing protective immunity and limiting the spread of disease. Heterologous prime‐boost vaccination based on the selection of different vaccine formulations and administration routes for priming and booster doses presents a promising strategy for inducing broader immune responses in key systemic and respiratory mucosal compartments. Intranasal vaccination can induce mucosal immune responses at the site of SARS‐CoV‐2 infection; however, the lack of clinically approved mucosal adjuvants makes it difficult to induce robust immune responses with protein subunit vaccines. Herein, we evaluated the immunogenicity of heterologous prime‐boost regimens in mice and hamsters based on a parenteral vaccination of the antigen in combination with sulfated lactosylarchaeol (SLA) archaeosomes, a liposome adjuvant comprised of a single semisynthetic archaeal lipid, followed by an intranasally administered unadjuvanted SARS‐CoV‐2 spike antigen. Intranasal administration of unadjuvanted spike to mice and hamsters increased serum spike‐specific IgG titers and spike‐neutralizing activity compared with nonboosted animals. Spike‐specific IgA responses were also detected in the bronchoalveolar lavage fluid in the lungs of mice that received an intranasal boost. In hamsters, the intranasal boost showed high efficacy against SARS‐CoV‐2 infection by protecting from body weight loss and reducing viral titers in the lungs and nasal turbinate. Overall, our heterologous intramuscular prime‐intranasal boost with SLA‐adjuvanted and unadjuvanted spike, respectively, demonstrated the potential of protein subunit formulations to promote antigen‐specific systemic and mucosal immune responses.

mRNA Technology and Mucosal Immunization

“…The proposal of mucosal mRNA vaccines carried within EVs obtained from edible plants appears viable since—as suggested by our experience with animals—no adjuvants are needed, no safety concerns emerged from the experimental studies, and the mucosal response to a viral vaccine has been satisfactory both in the digestive and respiratory tracts. This is in line with recent results in parenterally primed animals that demonstrate the efficacy of intranasal immunization with a non-adjuvanted virus protein [ 125 ]. Similarly, recent data on humans indicate that combinations of parenteral and mucosal vaccinations can both provide systemic protection and diminish the interhuman transmission of microbial agents [ 29 ].…”