An innovative nasal vaccine strategy to combat COVID

The respiratory mucosa is the primary site of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in humans. However at this site, parenteral vaccination regimens cannot induce adequate protective immunity. Relying on intramuscular administration, these vaccines have been shown to induce high levels of circulating antibodies, memory B cells, and circulating effector cluster of differentiation (CD)4+ and CD8+ T cells in preclinical and clinical models. However, they fail to induce tissue-resident memory B (BRM) cells and T (TRM) cells and mucosal immunoglobulin G (IgG) and dimeric IgA. Recent preclinical assessments of vaccines delivered intranasally (IN) induced adequate mucosal immunogenicity at respiratory mucosa. They also conferred immune protection and reduced viral shedding in mice, hamsters, and nonhuman primates. Further, they induced cross-reactive immunity against sarbecoviruses.



Researchers hypothesized systemic priming with messenger ribonucleic acid (mRNA)-lipid nanoparticle (LNP) followed by IN boosting conferred adequate protective immunity, unlike parenteral vaccination.

So they vaccinated K18-hACE2 mice with mRNA-based BNT162b2 vaccine IM - the prime dose. After 14 days, they intranasally (IN) administered an unadjuvanted SARS-CoV-2 spike - the booster dose. The team used divergent unadjuvanted intranasal SARS-CoV-2 spike boosters or an immunosilent polyplex encapsulating spike mRNA. They euthanized these mice at days 21 or 28 to assess for mucosal humoral immunity.

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