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+ 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.
Highlights
Introduction As witnessed over the last2 years, the rapid and global expansion of the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)[1], is a continued crisis affecting public health and the global economy
Spike structural protein, which embeds in the viral surface envelope, is the main protein used as a target in COVID-19 vaccines, and the receptor-binding domain (RBD) of spike is the major target for neutralizing antibodies that interfere with viral receptor binding[8]
The binding and neutralizing antibody responses were both developed as early as 14 days after the first administration of the two vaccine candidates, with endpoint IgG titers of 7108 and 5489 (GMT, AdC68-S), and pseudovirus-based neutralizing titer 50 (NT50) of 125 (GMT, AdC6-S) and 67(GMT, AdC68-S)
Summary
Introduction As witnessed over the last2 years, the rapid and global expansion of the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)[1], is a continued crisis affecting public health and the global economy. Chinese scientists first published the whole-genome sequence of SARS-CoV-22, and ever since, multiple research programs and vaccine industries have participated in vaccine development. Several manufacturers have successfully developed COVID-19 vaccines based on various platforms and strategies, and some of these vaccines have been authorized or approved for emergency use in some countries, with several more in different stages of clinical trials[3]. Poor neutralizing potency against B.1.351 variant was observed in specimens obtained from participants in clinical trials of several COVID-19 vaccines[9,10]. As new mutations are constantly being reported, eliciting higher and broader protective immune responses is urgent for the development of COVID-19 vaccines, and a heterologous primeboost strategy based on existing vaccine candidates may be a fast, safe, and economical way to achieve this goal
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