Comparative characterization of antibody responses induced by Ad5-vectored spike proteins of emerging SARS-CoV-2 VOCs

Abstract

Highly divergent SARS-CoV-2 variants have continuously emerged and spread around the world, and updated vaccines and innovative vaccination strategies are urgently needed to address the global SARS-COV2 pandemic. Here, we established a series of Ad5-vectored SARS-CoV-2 variant vaccines encoding multiple spike proteins derived from the Alpha, Beta, Gamma, Epsilon, Kappa, Delta and Omicron lineages and analyzed the antibody immune responses induced by single-dose and prime-boost vaccination strategies against emerging SARS-CoV-2 variants of concern (VOCs). Single-dose vaccination with SARS-CoV-2 variant vaccines tended to elicit the optimal self-matched neutralizing effects, and Ad5-B.1.351 produced more broad-spectrum cross-neutralizing antibodies against diverse variants. In contrast, prime-boost vaccination further strengthened and broadened the neutralizing antibody responses against highly divergent SARS-CoV-2 variants. The heterologous administration of Ad5-B.1.617.2 and Ad5-B.1.429 to Ad5-WT-primed mice resulted in superior antibody responses against most VOCs. In particular, the Omicron spike could only stimulate self-matched neutralizing antibodies with infrequent cross-reactivities to other variants used in single-dose vaccination strategies; moreover, with prime-boost regimens, this vaccine elicited an optimal specific neutralizing antibody response to Omicron, and prompted cross-antibody responses against other VOCs that were very similar to those obtained with Ad5-WT booster. Overall, this study delineated the unique characteristics of antibody responses to the SARS-CoV-2 VOC spikes with the single-dose or prime-boost vaccination strategies and provided insight into the vaccine development of next SARS-CoV-2 VOCs.

Heterologous prime-boost immunisation with mRNA- and AdC68-based 2019-nCoV variant vaccines induces broad-spectrum immune responses in mice

“…Numerous studies have indicated that 2019-nCoV Beta variant-specific COVID-19 vaccines induce broader spectrum immune responses against emerging 2019-nCoV variants than other variant-specific COVID-19 vaccines ( 9 , 29 ). Our results demonstrated that single-dose immunisation with AdB could induce broader-spectrum NAb titres than AdW against different 2019-nCoV variants.…”

“…Although Omicron-specific vaccines induce high neutralising activity against Omicron, they are not effective against other variants ( 9 , 10 ). COVID-19 vaccines expressing spike proteins from only Beta or Delta variants showed low immunogenicity, but induced relatively broad-spectrum neutralising antibodies against multiple variants ( 9 , 10 , 12 ). Moreover, the nucleocapsid (N) protein is highly conserved and immunogenic among 2019-nCoV variants and other coronaviruses.…”

“…Novel 2019-nCoV variant vaccines induce immune responses against different 2019-nCoV variants in mice (9)(10)(11)(12). Although Omicron-specific vaccines induce high neutralising activity against Omicron, they are not effective against other variants (9,10).…”

“…Novel 2019-nCoV variant vaccines induce immune responses against different 2019-nCoV variants in mice (9)(10)(11)(12). Although Omicron-specific vaccines induce high neutralising activity against Omicron, they are not effective against other variants (9,10). COVID-19 vaccines expressing spike proteins from only Beta or Delta variants showed low immunogenicity, but induced relatively broad-spectrum neutralising antibodies against multiple variants (9,10,12).…”

Effects of SARS-CoV-2 Omicron BA.1 Spike Mutations on T-Cell Epitopes in Mice

“…The SARS-CoV-2 vaccines Ad5-Spike-WT (also known as Ad5-nCoV) and Ad5-Spike-BA.1 were prepared by CanSino Biotechnology Inc. (Tianjin, China), as described in previous studies [ 7 , 25 ]. Specific-pathogen-free wild-type BALB/c (H-2 d ) and C57BL/6 (H-2 b ) mice were obtained from Beijing Vital River Laboratory Animal Technologies Co., Ltd. (Beijing, China) and SPF Biotechnology Co., Ltd. (Beijing, China), respectively.…”