A safe and effective vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is urgently needed to tackle the COVID-19 global pandemic. Here, we describe the development of chimpanzee adenovirus serotypes 6 and 68 (AdC6 and AdC68) vector-based vaccine candidates expressing the full-length transmembrane spike glycoprotein. We assessed the vaccine immunogenicity, protective efficacy, and immune cell profiles using single-cell RNA sequencing in mice. Mice were vaccinated via the intramuscular route with the two vaccine candidates using prime-only regimens or heterologous prime-boost regimens. Both chimpanzee adenovirus-based vaccines elicited strong and long-term antibody and T cell responses, balanced Th1/Th2 cell responses, robust germinal center responses, and provided effective protection against SARS-CoV-2 infection in mouse lungs. Strikingly, we found that heterologous prime-boost immunization induced higher titers of protective antibodies, and more spike-specific memory CD8 + T cells in mice. Potent neutralizing antibodies produced against the highly transmissible SARS-CoV-2 variants B.1.1.7 lineage (also known as N501Y.V1) and B.1.351 lineage (also known as N501Y.V2) were detectable in mouse sera over 6 months after prime immunization. Our results demonstrate that the heterologous prime-boost strategy with chimpanzee adenovirus-based vaccines is promising for further development to prevent SARS-CoV-2 infection.
【저자키워드】 immunology, Biological techniques, 【초록키워드】 COVID-19, neutralizing antibody, SARS-CoV-2, Efficacy, Vaccine, coronavirus, antibody, B.1.351, SARS-COV-2 infection, SARS-CoV-2 variant, CD8, Single-cell RNA sequencing, B.1.1.7 lineage, memory, Adenovirus, global pandemic, T cell, protective antibodies, mice, sera, Lungs, T cell responses, Lineage, vaccine candidate, glycoprotein, potent, Protective, intramuscular, Immune cell, Safe, heterologous prime-boost, regimen, acute respiratory syndrome, serotype, profile, regimens, full-length, responses, Prevent, effective, Cell, prime immunization, robust, produced, detectable, provided, expressing, the vaccine, elicited, adenovirus-based, heterologous prime-boost immunization, transmembrane spike, 【제목키워드】 SARS-COV-2 infection, immunization, protective immunity, adenoviral vector, elicit,