Comparison of the immunogenicity of nasal‐spray rVSV vector, adenovirus vector, and inactivated COVID‐19‐based vaccines in rodent models

Abstract Intranasal (i.n.) vaccines can induce mucosal and systemic immunity against respiratory pathogens. Previously, we demonstrated that the recombinant vesicular stomatitis virus (rVSV)‐based COVID‐19 vaccine rVSV‐SARS‐CoV‐2, with poor immunogenicity via the intramuscular route (i.m.), is more suitable for i.n. administration in mice and nonhuman primates. Here, we found that the rVSV‐SARS‐CoV‐2 Beta variant was more immunogenic than the wild‐type strain and other variants of concern (VOCs) in golden Syrian hamsters. Furthermore, the immune responses elicited by rVSV‐based vaccine candidates via the i.n. route were significantly higher than those of two licensed vaccines: the inactivated vaccine KCONVAC delivered via the i.m. route and the adenovirus‐based Vaxzevria delivered i.n. or i.m. We next assessed the booster efficacy of rVSV following two i.m. doses of KCONVAC. Twenty‐eight days after receiving two i.m. doses of KCONVAC, hamsters were boosted with a third dose of KCONVAC (i.m.), Vaxzevria (i.m. or i.n.), or rVSVs (i.n.). Consistent with other heterologous booster studies, Vaxzevria and rVSV elicited significantly higher humoral immunity than the homogenous KCONVAC. In summary, our results confirmed that two i.n. doses of rVSV‐Beta elicited significantly higher humoral immune responses than commercial inactivated and adeno‐based COVID vaccines in hamsters. As a heterologous booster dose, rVSV‐Beta induced potent, persistent, and broad‐spectrum humoral and mucosal neutralizing responses against all VOCs, highlighting its potential to be developed into a nasal‐spray vaccine.