Fig. 1
Mucosal immunization with a trivalent ChAd-vectored vaccine induces superior protection against ancestral SARS-CoV-2 and variants of concern. a Three different SARS-CoV-2 antigen domains (S1 Spike Protein (S1), nucleocapsid (N), RNA-dependent RNA polymerase (RdRp)) were cloned into either human (Tri:HuAd) or chimpanzee (Tri:ChAd) adenoviral vectors. BALB/c mice were immunized either intranasal (i.n.) or intramuscular (i.m.) prior to lethal SARS-CoV-2 challenge. b Results of the comparative analyses utilizing both the two different vector platforms and routes of application (i.n. vs. i.m.). Mucosal immunization (i.n.) with the Tri:ChAd vaccine induced overall superior immune responses: increased production of systemic and local IgG and IgA antibodies, markedly enhanced antibody neutralization capacity, a strong induction of multifunctional CD8+ T cell responses as well as the strong activation of TRM and TII. I.n. vaccinated mice infected with an otherwise lethal dose of SARS-CoV-2 showed no body weight loss and a significant decrease of viral burden. c Schematic representation of the three different chimpanzee adenoviral constructs: the trivalent (S1, N, RdRp), bivalent (N, RdRp) and monovalent (S1) vaccines. Mucosal delivery of the trivalent vaccine exhibits highest protective efficacy against SARS-CoV-2 and varianst of concern (VOC) indicated by prevention of morbidity (body weight loss) and a significant decrease in viral burden compared to mice that received the bivalent or monovalent vaccines. d The optimal vaccination strategy against both SARS-CoV-2 and VOC was proven to be an intranasal application of a trivalent vaccine using the chimpanzee adenoviral vector platform. Created with BioRender.com
