tetano
Editor, Senior Moderator
ACS Infect Dis
. 2022 Jun 24.
doi: 10.1021/acsinfecdis.2c00259. Online ahead of print.
Adjuvant-Protein Conjugate Vaccine with Built-In TLR7 Agonist on S1 Induces Potent Immunity against SARS-CoV-2 and Variants of Concern
Ru-Yan Zhang[SUP] 1 [/SUP], Shi-Hao Zhou[SUP] 1 [/SUP], Chen-Bin He[SUP] 1 [/SUP], Jian Wang[SUP] 1 [/SUP], Yu Wen[SUP] 1 [/SUP], Ran-Ran Feng[SUP] 1 [/SUP], Xu-Guang Yin[SUP] 1 [/SUP], Guang-Fu Yang[SUP] 1 [/SUP], Jun Guo[SUP] 1 [/SUP]
Affiliations
Abstract
With the global pandemic of the new coronavirus disease (COVID-19), a safe, effective, and affordable mass-produced vaccine remains the current focus of research. Herein, we designed an adjuvant-protein conjugate vaccine candidate, in which the TLR7 agonist (TLR7a) was conjugated to S1 subunit of SARS-CoV-2 spike protein, and systematically compared the effect of different numbers of built-in TLR7a on the immune activity for the first time. As the number of built-in TLR7a increased, a bell-shaped reaction was observed in three TLR7a-S1 conjugates, with TLR7a(10)-S1 (with around 10 built-in adjuvant molecules on one S1 protein) eliciting a more potent immune response than TLR7a(2)-S1 and TLR7a(18)-S1. This adjuvant-protein conjugate strategy allows the built-in adjuvant to provide cluster effects and prevents systemic toxicity and facilitates the co-delivery of adjuvant and antigen. Vaccination of mice with TLR7a(10)-S1 triggered a potent humoral and cellular immunity and a balanced Th1/Th2 immune response. Meanwhile, the vaccine induces effective neutralizing antibodies against SARS-CoV-2 and all variants of concern (B.1.1.7/alpha, B.1.351/beta, P.1/gamma, B.1.617.2/delta, and B.1.1.529/omicron). It is expected that the adjuvant-protein conjugate strategy has great potential to construct a potent recombinant protein vaccine candidate against various types of diseases.
Keywords: COVID-19; SARS-CoV-2; TLR7 agonist; adjuvant-protein conjugate; recombinant protein vaccine.
. 2022 Jun 24.
doi: 10.1021/acsinfecdis.2c00259. Online ahead of print.
Adjuvant-Protein Conjugate Vaccine with Built-In TLR7 Agonist on S1 Induces Potent Immunity against SARS-CoV-2 and Variants of Concern
Ru-Yan Zhang[SUP] 1 [/SUP], Shi-Hao Zhou[SUP] 1 [/SUP], Chen-Bin He[SUP] 1 [/SUP], Jian Wang[SUP] 1 [/SUP], Yu Wen[SUP] 1 [/SUP], Ran-Ran Feng[SUP] 1 [/SUP], Xu-Guang Yin[SUP] 1 [/SUP], Guang-Fu Yang[SUP] 1 [/SUP], Jun Guo[SUP] 1 [/SUP]
Affiliations
- PMID: 35748575
- DOI: 10.1021/acsinfecdis.2c00259
Abstract
With the global pandemic of the new coronavirus disease (COVID-19), a safe, effective, and affordable mass-produced vaccine remains the current focus of research. Herein, we designed an adjuvant-protein conjugate vaccine candidate, in which the TLR7 agonist (TLR7a) was conjugated to S1 subunit of SARS-CoV-2 spike protein, and systematically compared the effect of different numbers of built-in TLR7a on the immune activity for the first time. As the number of built-in TLR7a increased, a bell-shaped reaction was observed in three TLR7a-S1 conjugates, with TLR7a(10)-S1 (with around 10 built-in adjuvant molecules on one S1 protein) eliciting a more potent immune response than TLR7a(2)-S1 and TLR7a(18)-S1. This adjuvant-protein conjugate strategy allows the built-in adjuvant to provide cluster effects and prevents systemic toxicity and facilitates the co-delivery of adjuvant and antigen. Vaccination of mice with TLR7a(10)-S1 triggered a potent humoral and cellular immunity and a balanced Th1/Th2 immune response. Meanwhile, the vaccine induces effective neutralizing antibodies against SARS-CoV-2 and all variants of concern (B.1.1.7/alpha, B.1.351/beta, P.1/gamma, B.1.617.2/delta, and B.1.1.529/omicron). It is expected that the adjuvant-protein conjugate strategy has great potential to construct a potent recombinant protein vaccine candidate against various types of diseases.
Keywords: COVID-19; SARS-CoV-2; TLR7 agonist; adjuvant-protein conjugate; recombinant protein vaccine.