Abstract
Antigen-specific tissue-resident memory T cells (Trms) and neutralizing IgA antibodies provide the most effective protection of the lungs from viral infections. To induce those essential components of lung immunity against SARS-CoV-2, we tested various immunization protocols involving intranasal delivery of a novel Modified Vaccinia virus Ankara (MVA)-SARS-2-spike vaccine candidate. We show that a single intranasal MVA-SARS-CoV-2-S application in mice strongly induced pulmonary spike-specific CD8+ T cells, albeit restricted production of neutralizing antibodies. In prime-boost protocols, intranasal booster vaccine delivery proved to be crucial for a massive expansion of systemic and lung tissue-resident spike-specific CD8+ T cells and the development of Th1 - but not Th2 - CD4+ T cells. Likewise, very high titers of IgG and IgA anti-spike antibodies were present in serum and broncho-alveolar lavages that possessed high virus neutralization capacities to all current SARS-CoV-2 variants of concern. Importantly, the MVA-SARS-2-spike vaccine applied in intramuscular priming and intranasal boosting treatment regimen completely protected hamsters from developing SARS-CoV-2 lung infection and pathology. Together, these results identify intramuscular priming followed by respiratory tract boosting with MVA-SARS-2-S as a promising approach for the induction of local, respiratory as well as systemic immune responses suited to protect from SARS-CoV-2 infections.
Highlights
Large vaccination campaigns started at the beginning of 2021 to combat the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic
Our study showed that respiratory delivery of a MVA-SARS-2-S vaccine efficiently protected hamsters from SARS-CoV-2 infection
The rapid clearance of SARS-CoV-2 combined with the minimal immune response can only be attributed to the existence of two major pillars of adaptive immunity in the respiratory tract: the local production and secretion of IgA antibodies and tissue resident memory T cells directed against the spike protein
Summary
Large vaccination campaigns started at the beginning of 2021 to combat the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. In contrast to intramuscular vaccine application, inhalative vaccination induces high levels of antigen-specific IgA antibodies and tissue-resident memory T cells (Trms) in the respiratory tract [17,18,19]. Upon re-infection, Trms get rapidly activated, secrete cytokines, proliferate, and recruit other leukocytes, enabling accelerated clearance of the pathogens [22]. Along these lines, respiratory delivery of coronavirus 2019 (COVID-19) vaccine candidates induced robust lung immunity and protected against SARS-CoV-2 infection [23,24,25,26]. Inhaled COVID-19 vaccine candidate based on parainfluenza virus type 5 vector efficiently blocked animal-to-animal transmission of the SARS-CoV-2 [27]. There are several COVID-19 vaccine candidates in development for inhaled administration [28] and the latest clinical results proved safety and immunogenicity of aerosolized adenovirus type-5 vector-based COVID-19 vaccine [29]
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