Cell Discovery (Feb 2022)

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

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

DOI
https://doi.org/10.1038/s41421-021-00370-2
Journal volume & issue
Vol. 8, no. 1
pp. 1 – 16

Abstract

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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.