tetano
Editor, Senior Moderator
Cell Discov
. 2021 Dec 18;7(1):123.
doi: 10.1038/s41421-021-00360-4.
Heterologous prime-boost immunizations with chimpanzee adenoviral vectors elicit potent and protective immunity against SARS-CoV-2 infection
Jiaojiao Liu[SUP] #[/SUP][SUP] 1 [/SUP], Kun Xu[SUP] #[/SUP][SUP] 2 3 [/SUP], Man Xing[SUP] #[/SUP][SUP] 1 [/SUP], Yue Zhuo[SUP] #[/SUP][SUP] 1 [/SUP], Jingao Guo[SUP] #[/SUP][SUP] 4 5 [/SUP], Meng Du[SUP] 1 [/SUP], Qi Wang[SUP] 1 [/SUP], Yaling An[SUP] 6 [/SUP], Jinhe Li[SUP] 3 4 [/SUP], Ping Gao[SUP] 3 4 [/SUP], Yihan Wang[SUP] 1 [/SUP], Furong He[SUP] 1 [/SUP], Yingying Guo[SUP] 1 [/SUP], Mingxi Li[SUP] 7 [/SUP], Yuchao Zhang[SUP] 8 9 [/SUP], Linqi Zhang[SUP] 7 [/SUP], George F Gao[SUP] 10 11 12 [/SUP], Lianpan Dai[SUP] 13 14 15 [/SUP], Dongming Zhou[SUP] 16 17 [/SUP]
Affiliations
Abstract
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[SUP]+[/SUP] 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.
. 2021 Dec 18;7(1):123.
doi: 10.1038/s41421-021-00360-4.
Heterologous prime-boost immunizations with chimpanzee adenoviral vectors elicit potent and protective immunity against SARS-CoV-2 infection
Jiaojiao Liu[SUP] #[/SUP][SUP] 1 [/SUP], Kun Xu[SUP] #[/SUP][SUP] 2 3 [/SUP], Man Xing[SUP] #[/SUP][SUP] 1 [/SUP], Yue Zhuo[SUP] #[/SUP][SUP] 1 [/SUP], Jingao Guo[SUP] #[/SUP][SUP] 4 5 [/SUP], Meng Du[SUP] 1 [/SUP], Qi Wang[SUP] 1 [/SUP], Yaling An[SUP] 6 [/SUP], Jinhe Li[SUP] 3 4 [/SUP], Ping Gao[SUP] 3 4 [/SUP], Yihan Wang[SUP] 1 [/SUP], Furong He[SUP] 1 [/SUP], Yingying Guo[SUP] 1 [/SUP], Mingxi Li[SUP] 7 [/SUP], Yuchao Zhang[SUP] 8 9 [/SUP], Linqi Zhang[SUP] 7 [/SUP], George F Gao[SUP] 10 11 12 [/SUP], Lianpan Dai[SUP] 13 14 15 [/SUP], Dongming Zhou[SUP] 16 17 [/SUP]
Affiliations
- PMID: 34923570
- DOI: 10.1038/s41421-021-00360-4
Abstract
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[SUP]+[/SUP] 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.