Abstract
The emerging SARS-CoV-2 variants of concern (VOCs) threaten the effectiveness of current COVID-19 vaccines administered intramuscularly and designed to only target the spike protein. There is a pressing need to develop next-generation vaccine strategies for broader and long-lasting protection. Using adenoviral vectors (Ad) of human and chimpanzee origin, we evaluated Ad-vectored trivalent COVID-19 vaccines expressing spike-1, nucleocapsid, and RdRp antigens in murine models. We show that single-dose intranasal immunization, particularly with chimpanzee Ad-vectored vaccine, is superior to intramuscular immunization in induction of the tripartite protective immunity consisting of local and systemic antibody responses, mucosal tissue-resident memory T cells and mucosal trained innate immunity. We further show that intranasal immunization provides protection against both the ancestral SARS-CoV-2 and two VOC, B.1.1.7 and B.1.351. Our findings indicate that respiratory mucosal delivery of Ad-vectored multivalent vaccine represents an effective next-generation COVID-19 vaccine strategy to induce all-around mucosal immunity against current and future VOC.
Keywords: COVID-19; SARS-CoV-2; T cell immunity; adenoviral vector; animal models; chimpanzee adenoviral vector; human adenoviral vector; humoral immunity; intramuscular immunization; multi-valent vaccine; next-generation vaccines; respiratory mucosal immunity; respiratory mucosal immunization; trained innate immunity; variants of concern.
【저자키워드】 COVID-19, SARS-CoV-2, variants of concern, T cell immunity, animal models, Humoral immunity, adenoviral vector, chimpanzee adenoviral vector, human adenoviral vector, intramuscular immunization, multi-valent vaccine, next-generation vaccines, respiratory mucosal immunity, respiratory mucosal immunization, trained innate immunity, 【초록키워드】 Vaccine, COVID-19 vaccine, Immunity, antibody, Innate immunity, VoC, B.1.351, T cells, SARS-CoV-2 variant, variants of concern, Local, animal models, immunization, variants, Spike protein, Antigen, Humoral immunity, T cell, protective immunity, B.1.1.7, nucleocapsid, adenoviral vectors, memory T cells, VOCs, Effectiveness, RdRP, adenoviral vector, respiratory, memory T cell, intranasal, multivalent vaccine, intramuscular, mucosal, humoral, Single-dose, murine models, trivalent, Administered, responses, effective, develop, evaluated, provide, the spike protein, long-lasting, induce, expressing, intramuscularly, 【제목키워드】 COVID-19 vaccine, variant, mucosal, strain, robust, provide,