tetano
Editor, Senior Moderator
Microbiol Spectr
. 2023 Feb 27;e0268722.
doi: 10.1128/spectrum.02687-22. Online ahead of print.
A Beta Strain-Based Spike Glycoprotein Vaccine Candidate Induces Broad Neutralization and Protection against SARS-CoV-2 Variants of Concern
Lei Cao[SUP] #[/SUP][SUP] 1 [/SUP], Jinyuan Guo[SUP] #[/SUP][SUP] 1 [/SUP], Hai Li[SUP] #[/SUP][SUP] 1 [/SUP], Hu Ren[SUP] #[/SUP][SUP] 1 [/SUP], Kang Xiao[SUP] 1 [/SUP], Yan Zhang[SUP] 1 [/SUP], Shuangli Zhu[SUP] 1 [/SUP], Yang Song[SUP] 1 [/SUP], Weijia Zhao[SUP] 2 [/SUP], Dan Wu[SUP] 2 [/SUP], Zhihui Chen[SUP] 2 [/SUP], Yanan Zhang[SUP] 1 3 [/SUP], Baicheng Xia[SUP] 1 [/SUP], Tianjiao Ji[SUP] 1 [/SUP], Dongmei Yan[SUP] 1 [/SUP], Dongyan Wang[SUP] 1 [/SUP], Qian Yang[SUP] 1 [/SUP], Yangzi Zhou[SUP] 1 [/SUP], Xiaolei Li[SUP] 1 [/SUP], Zhanjun Hou[SUP] 2 [/SUP], Wenbo Xu[SUP] 1 4 [/SUP]
Affiliations
Abstract
The coronavirus disease 2019 (COVID-19) pandemic is still ongoing. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) are circulating worldwide, making it resistant to existing vaccines and antiviral drugs. Therefore, the evaluation of variant-based expanded spectrum vaccines to optimize the immune response and provide broad protectiveness is very important. In this study, we expressed spike trimer protein (S-TM) based on the Beta variant in a GMP-grade workshop using CHO cells. Mice were immunized twice with S-TM protein combined with aluminum hydroxide (Al) and CpG Oligonucleotides (CpG) adjuvant to evaluate its safety and efficacy. BALB/c immunized with S-TM + Al + CpG induced high neutralizing antibody titers against the Wuhan-Hu-1 strain (wild-type, WT), the Beta and Delta variants, and even the Omicron variant. In addition, compared with the S-TM + Al group, the S-TM + Al + CpG group effectively induced a stronger Th1-biased cell immune response in mice. Furthermore, after the second immunization, H11-K18 hACE2 mice were well protected from challenge with the SARS-CoV-2 Beta strain, with a 100% survival rate. The virus load and pathological lesions in the lungs were significantly reduced, and no virus was detected in mouse brain tissue. Our vaccine candidate is practical and effective for current SARS-CoV-2 VOCs, which will support its further clinical development for potential sequential immune and primary immunization. IMPORTANCE Continuous emergence of adaptive mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to challenge the use and development of existing vaccines and drugs. The value of variant-based vaccines that are capable of inducing a higher and broader protection immune response against SARS-CoV-2 variants is currently being evaluated. This article shows that a recombinant prefusion spike protein based on a Beta variant was highly immunogenic and could induced a stronger Th1-biased cell immune response in mice and was effectively protective against challenge with the SARS-CoV-2 Beta variant. Importantly, this Beta-based SARS-CoV-2 vaccine could also offer a robust humoral immune response with effectively broad neutralization ability against the wild type and different variants of concern (VOCs): the Beta, Delta, and Omicron BA.1 variants. To date, the vaccine described here has been produced in a pilot scale (200L), and the development, filling process, and toxicological safety evaluation have also been completed, which provides a timely response to the emerging SARS-CoV-2 variants and vaccine development.
Keywords: SARS-CoV-2; broad neutralization; spike glycoprotein; variant-based vaccine; variants of concern.
. 2023 Feb 27;e0268722.
doi: 10.1128/spectrum.02687-22. Online ahead of print.
A Beta Strain-Based Spike Glycoprotein Vaccine Candidate Induces Broad Neutralization and Protection against SARS-CoV-2 Variants of Concern
Lei Cao[SUP] #[/SUP][SUP] 1 [/SUP], Jinyuan Guo[SUP] #[/SUP][SUP] 1 [/SUP], Hai Li[SUP] #[/SUP][SUP] 1 [/SUP], Hu Ren[SUP] #[/SUP][SUP] 1 [/SUP], Kang Xiao[SUP] 1 [/SUP], Yan Zhang[SUP] 1 [/SUP], Shuangli Zhu[SUP] 1 [/SUP], Yang Song[SUP] 1 [/SUP], Weijia Zhao[SUP] 2 [/SUP], Dan Wu[SUP] 2 [/SUP], Zhihui Chen[SUP] 2 [/SUP], Yanan Zhang[SUP] 1 3 [/SUP], Baicheng Xia[SUP] 1 [/SUP], Tianjiao Ji[SUP] 1 [/SUP], Dongmei Yan[SUP] 1 [/SUP], Dongyan Wang[SUP] 1 [/SUP], Qian Yang[SUP] 1 [/SUP], Yangzi Zhou[SUP] 1 [/SUP], Xiaolei Li[SUP] 1 [/SUP], Zhanjun Hou[SUP] 2 [/SUP], Wenbo Xu[SUP] 1 4 [/SUP]
Affiliations
- PMID: 36847495
- DOI: 10.1128/spectrum.02687-22
Abstract
The coronavirus disease 2019 (COVID-19) pandemic is still ongoing. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) are circulating worldwide, making it resistant to existing vaccines and antiviral drugs. Therefore, the evaluation of variant-based expanded spectrum vaccines to optimize the immune response and provide broad protectiveness is very important. In this study, we expressed spike trimer protein (S-TM) based on the Beta variant in a GMP-grade workshop using CHO cells. Mice were immunized twice with S-TM protein combined with aluminum hydroxide (Al) and CpG Oligonucleotides (CpG) adjuvant to evaluate its safety and efficacy. BALB/c immunized with S-TM + Al + CpG induced high neutralizing antibody titers against the Wuhan-Hu-1 strain (wild-type, WT), the Beta and Delta variants, and even the Omicron variant. In addition, compared with the S-TM + Al group, the S-TM + Al + CpG group effectively induced a stronger Th1-biased cell immune response in mice. Furthermore, after the second immunization, H11-K18 hACE2 mice were well protected from challenge with the SARS-CoV-2 Beta strain, with a 100% survival rate. The virus load and pathological lesions in the lungs were significantly reduced, and no virus was detected in mouse brain tissue. Our vaccine candidate is practical and effective for current SARS-CoV-2 VOCs, which will support its further clinical development for potential sequential immune and primary immunization. IMPORTANCE Continuous emergence of adaptive mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to challenge the use and development of existing vaccines and drugs. The value of variant-based vaccines that are capable of inducing a higher and broader protection immune response against SARS-CoV-2 variants is currently being evaluated. This article shows that a recombinant prefusion spike protein based on a Beta variant was highly immunogenic and could induced a stronger Th1-biased cell immune response in mice and was effectively protective against challenge with the SARS-CoV-2 Beta variant. Importantly, this Beta-based SARS-CoV-2 vaccine could also offer a robust humoral immune response with effectively broad neutralization ability against the wild type and different variants of concern (VOCs): the Beta, Delta, and Omicron BA.1 variants. To date, the vaccine described here has been produced in a pilot scale (200L), and the development, filling process, and toxicological safety evaluation have also been completed, which provides a timely response to the emerging SARS-CoV-2 variants and vaccine development.
Keywords: SARS-CoV-2; broad neutralization; spike glycoprotein; variant-based vaccine; variants of concern.