RBD conjugate vaccine with a built-in TLR1/2 agonist is highly immunogenic against SARS-CoV-2 and variants of concern

Zhou, Shihao; Zhang, Ruyan; Zhang, Haiwei; Liu, Yanling; Wen, Yiping; Wang, Jian; Li, Yuting; You, Zi-Wei; Yin, Xuguang; Qiu, Hong; Gong, Rui; Yang, Guang‐Fu; Guo, Jun

doi:10.1039/d1cc06520c

Cited by 19 publications

(29 citation statements)

References 37 publications

(4 reference statements)

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“…Female BALB/c mice aged 6 weeks were vaccinated on days 1, 15, and 29 for subcutaneous injection (200 mL per mouse), and the sera were collected on days 14, 28, and 42 to evaluate the antibody immune responses including enzyme linked immunosorbent assay (ELISA), fluorescence-activated cell sorting (FACS) analysis, and complement-dependent cytotoxicity (CDC) assay (48)(49)(50). In addition, the spleens from mice were collected on days 42 to evaluate the cellular immune responses including cytotoxic T lymphocyte (CTL) assay, intracellular cytokine staining (ICS) assay, and enzyme-linked immunospot (ELISpot) assay (51)(52)(53)(54). All mice used in the experiments were purchased and bred in the Laboratory Animal Centre of Huazhong Agriculture University, and the experiments were conducted strictly in accordance with the principles of welfare and ethics of medical laboratory animals.…”

Section: Vaccine Design and Immunizationmentioning

confidence: 99%

Alum Adjuvant and Built-in TLR7 Agonist Synergistically Enhance Anti-MUC1 Immune Responses for Cancer Vaccine

Zhou

Zhang

et al. 2022

Front. Immunol.

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The tumor-associated antigen mucin 1 (MUC1) is an attractive target of antitumor vaccine, but its weak immunogenicity is a big challenge for the development of vaccine. In order to enhance immune responses against MUC1, herein, we conjugated small molecular toll-like receptor 7 agonist (TLR7a) to carrier protein BSA via MUC1 glycopeptide to form a three-component conjugate (BSA-MUC1-TLR7a). Furthermore, we combined the three-component conjugate with Alum adjuvant to explore their synergistic effects. The immunological studies indicated that Alum adjuvant and built-in TLR7a synergistically enhanced anti-MUC1 antibody responses and showed Th1-biased immune responses. Meanwhile, antibodies elicited by the vaccine candidate effectively recognized tumor cells and induced complement-dependent cytotoxicity. In addition, Alum adjuvant and built-in TLR7a synergistically enhanced MUC1 glycopeptide-specific memory CD8+ T-cell immune responses. More importantly, the vaccine with the binary adjuvant can significantly inhibit tumor growth and prolong the survival time of mice in the tumor challenge experiment. This novel vaccine construct provides an effective strategy to develop antitumor vaccines.

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Section: Vaccine Design and Immunizationmentioning

confidence: 99%

Alum Adjuvant and Built-in TLR7 Agonist Synergistically Enhance Anti-MUC1 Immune Responses for Cancer Vaccine

Zhou

Zhang

et al. 2022

Front. Immunol.

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“…Pam3CSK4, TLR1/2 agonist, has been studied in combination with protein adjuvants as alternative vaccine for SARS-CoV-2. Studies about the vaccine showed that Pam3CSK4 protects organism against SARS-CoV-2 virus ( Zhou et al, 2022 ).…”

Section: Tlrs Sensing Of Sars-cov-2mentioning

confidence: 99%

Toll-like receptor (TLRs) agonists and antagonists for COVID-19 treatments

Liu

Yang

et al. 2022

Front. Pharmacol.

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Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) rapidly infects humans and animals which make coronavirus disease 2019 (COVID-19) a grievous epidemic worldwide which broke out in 2020. According to data analysis of the other coronavirus family, for instance severe acute respiratory syndrome SARS coronavirus (SARS-CoV), can provide experience for the mutation of SARS-CoV-2 and the prevention and treatment of COVID-19. Toll-like receptors (TLRs) as a pattern recognition receptor (PRRs), have an indispensable function in identifying the invader even activate the innate immune system. It is possible for organism to activate different TLR pathways which leads to secretion of proinflammatory cytokines such as Interleukin 1 (IL-1), Interleukin 6 (IL-6), Tumor necrosis factor α (TNFα) and type Ⅰ interferon. As a component of non-specific immunity, TLRs pathway may participate in the SARS-CoV-2 pathogenic processes, due to previous works have proved that TLRs are involved in the invasion and infection of SARS-CoV and MERS to varying degrees. Different TLR, such as TLR2, TLR4, TLR7, TLR8 and TLR9 probably have a double-sided in COVID-19 infection. Therefore, it is of great significance for a correctly acknowledging how TLR take part in the SARS-CoV-2 pathogenic processes, which will be the development of treatment and prevention strategies.

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“…In addition, we also investigated potent COVID-19 subunit vaccines using RBD as the protein antigen. 13 , 14 However, few studies have systematically compared these S subunits as vaccine antigens in immunological evaluation.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, a stabilized prefusion form of the S protein (S-trimer) was achieved by adding two stabilizing proline mutations in the C-terminal S2 fusion in previous research. , Given their indispensable functions in viral infection, the S-trimer, , S-ECD (extracellular domain), S1, , and RBD , are ideal targets for developing subunit vaccines against SARS-CoV-2 and its variants. In addition, we also investigated potent COVID-19 subunit vaccines using RBD as the protein antigen. , However, few studies have systematically compared these S subunits as vaccine antigens in immunological evaluation.…”

Section: Introductionmentioning

confidence: 99%

MPLA-Adjuvanted Liposomes Encapsulating S-Trimer or RBD or S1, but Not S-ECD, Elicit Robust Neutralization Against SARS-CoV-2 and Variants of Concern

et al. 2022

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Safe and effective vaccines are the best method to defeat worldwide SARS-CoV-2 and its circulating variants. The SARS-CoV-2 S protein and its subunits are the most attractive targets for the development of protein-based vaccines. In this study, we evaluated three lipophilic adjuvants, monophosphoryl lipid A (MPLA), Toll-like receptor (TLR) 1/2 ligand Pam 3 CSK 4 , and α-galactosylceramide ( α -GalCer), in liposomal and nonliposomal vaccines. The immunological results showed that the MPLA-adjuvanted liposomal vaccine induced the strongest humoral and cellular immunity. Therefore, we further performed a systematic comparison of S-trimer, S-ECD, S1, and RBD as antigens in MPLA-adjuvanted liposomes and found that, although these four vaccines all induced robust specific antibody responses, only S-trimer, S1, and RBD liposomes, but not S-ECD, elicited potent neutralizing antibody responses. Moreover, RBD, S-trimer, and S1 liposomes effectively neutralized variants (B.1.1.7/alpha, B.1.351/beta, P.1/gamma, B.1.617.2/delta, and B.1.1.529/omicron). These results provide important information for the subunit vaccine design against SARS-CoV-2 and its variants.

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RBD conjugate vaccine with a built-in TLR1/2 agonist is highly immunogenic against SARS-CoV-2 and variants of concern

Abstract: The coronavirus 2019 (COVID-19) pandemic is causing serious impact in the world, safe and effective vaccines and medicines are the best method to combat the disease. The receptor-binding domain (RBD)...

Cited by 19 publications

References 37 publications

Alum Adjuvant and Built-in TLR7 Agonist Synergistically Enhance Anti-MUC1 Immune Responses for Cancer Vaccine

Alum Adjuvant and Built-in TLR7 Agonist Synergistically Enhance Anti-MUC1 Immune Responses for Cancer Vaccine

Toll-like receptor (TLRs) agonists and antagonists for COVID-19 treatments

MPLA-Adjuvanted Liposomes Encapsulating S-Trimer or RBD or S1, but Not S-ECD, Elicit Robust Neutralization Against SARS-CoV-2 and Variants of Concern

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