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.
【저자키워드】 Vaccine, vaccination, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Lungs, respiratory tract, bronchus-associated lymphoid tissue (BALT), modified vaccinia virus Ankara (MVA), spike (S) protein, 【초록키워드】 SARS-CoV-2, pathology, protocol, Immunity, Neutralizing antibodies, hamsters, T cells, Th1, Th2, SARS-CoV-2 variant, lung, Lung infection, Local, virus, CD4, CD8, viral infections, immunization, Antigen, serum, T cell, Viral, mice, IgA, immune responses, Lungs, memory T cells, Virus neutralization, vaccine candidate, Neutralizing, respiratory tract, hamster, respiratory, SARS-CoV-2 infections, memory T cell, anti-spike antibodies, intranasal, anti-spike antibody, intramuscular, Booster vaccine, protocols, followed by, systemic immune response, systemic immune responses, IgA antibodies, treatment regimen, priming, component, vaccinia, memory T, SARS-CoV-2-S, approach, effective, PROTECT, tested, identify, applied, induce, IgA antibody, titers of IgG, 【제목키워드】 SARS-CoV-2, pulmonary, delivery, vector, rodent, Against,