CoVac501, a self-adjuvanting peptide vaccine conjugated with TLR7 agonists, against SARS-CoV-2 induces protective immunity

Yiru Long,Jianhua Sun,Huilin Chen,Hong-Yi Zheng,Wei Huang,Yong Gan,Xiaoyan Pan,Jian‐Ping Zuo ,Ben Chen,Tingting Liu,Jianqing Xu,Weiliang Zhu,Yulong Miao ,Tian-Zhang Song,Xionghua Peng,Xiaoyan Zhang,Ji Zhou,Xin-Yan Long,Yachun Zhang,Leike Zhang,Qiuping Qin,Wei Tang,Zhijian Xu,Gengfu Xiao,Heng Li,Xiaowei Tong ,Mian Qin,Xinxin Zhang,Q An ,Peng Zhu,Yong‐Tang Zheng ,Pan Yu,Feng Tang,Jin Ren,Guangyi Jin,Longfei Ding,Datao Liu,Likun Gong

doi:10.1038/s41421-021-00370-2

Abstract

Safe, effective, and economical vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to achieve adequate herd immunity and end the pandemic. We constructed a novel SARS-CoV-2 vaccine, CoVac501, which is a self-adjuvanting peptide vaccine conjugated with Toll-like receptor 7 (TLR7) agonists. The vaccine contains immunodominant peptides screened from the receptor-binding domain (RBD) and is fully chemically synthesized. It has been formulated in an optimized nanoemulsion formulation and is stable at 40 °C for 1 month. In non-human primates (NHPs), CoVac501 elicited high and persistent titers of protective neutralizing antibodies against multiple RBD mutations, SARS-CoV-2 original strain, and variants (B.1.1.7 and B.1.617.2). Specific peptides booster immunization against the B.1.351 variant has also been shown to be effective in improving protection against B.1.351. Meanwhile, CoVac501 elicited the increase of memory T cells, antigen-specific CD8+ T-cell responses, and Th1-biased CD4+ T-cell immune responses in NHPs. Notably, at an extremely high SARS-CoV-2 challenge dose of 1 × 107 TCID50, CoVac501 provided near-complete protection for the upper and lower respiratory tracts of cynomolgus macaques.

Highlights

The uncontrolled transmission and ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lead to a requirement for safe, effective, quickly designable, and economical vaccines to rapidlyDistinguished from these platforms, the peptide vaccine platform has unique advantages as an alternative approach to meet the challenges
Several studies have shown that the receptor-binding domain (RBD) is an immunodominant region in the S protein, and neutralizing antibodies (NAbs) in convalescent patients’ sera are mostly against the RBD19–23
Screening of NAbs epitopes from the RBD for immunization holds promise for inducing specific and protective humoral immune responses

Summary

Introduction

The uncontrolled transmission and ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lead to a requirement for safe, effective, quickly designable, and economical vaccines to rapidly. Distinguished from these platforms, the peptide vaccine platform has unique advantages as an alternative approach to meet the challenges. TLR7 agonists are being developed in combination with various vaccines in our and others’ studies to facilitate the antigen presentation, activate innate immunity, promote antibody affinity maturation, and maintain long-lasting immune memory[13,14,15,16]

Methods

Results

Conclusion