A two-adjuvant multiantigen candidate vaccine induces superior protective immune responses against SARS-CoV-2 challenge
Wenwen Jiang,
Li Shi,
Lukui Cai,
Xiaoyu Wang,
Jingyan Li,
Heng Li,
Jiangli Liang,
Qin Gu,
Guang Ji,
Jing Li,
Longding Liu,
Mingbo Sun
Affiliations
Wenwen Jiang
Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming, Yunnan, China
Li Shi
Laboratory of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming, Yunnan, China
Lukui Cai
Laboratory of Vaccine Development, Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming, Yunnan, China
Xiaoyu Wang
Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming, Yunnan, China
Jingyan Li
Laboratory of Vaccine Development, Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming, Yunnan, China
Heng Li
Laboratory of Respiratory Infection, Kunming National High-level Biosafety Research Center, Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming, Yunnan, China
Jiangli Liang
Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming, Yunnan, China
Qin Gu
Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming, Yunnan, China
Guang Ji
Laboratory of Vaccine Development, Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming, Yunnan, China
Jing Li
Laboratory of Respiratory Infection, Kunming National High-level Biosafety Research Center, Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming, Yunnan, China
Longding Liu
Laboratory of Respiratory Infection, Kunming National High-level Biosafety Research Center, Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming, Yunnan, China; Corresponding author
Mingbo Sun
Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming, Yunnan, China; Laboratory of Vaccine Development, Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming, Yunnan, China; Corresponding author
Summary: An ideal vaccine against SARS-CoV-2 is expected to elicit broad immunity to prevent viral infection and disease, with efficient viral clearance in the upper respiratory tract (URT). Here, the N protein and prefusion-full S protein (SFLmut) are combined with flagellin (KF) and cyclic GMP-AMP (cGAMP) to generate a candidate vaccine, and this vaccine elicits stronger systemic and mucosal humoral immunity than vaccines containing other forms of the S protein. Furthermore, the candidate vaccine administered via intranasal route can enhance local immune responses in the respiratory tract. Importantly, human ACE2 transgenic mice given the candidate vaccine are protected against lethal SARS-CoV-2 challenge, with superior protection in the URT compared with that in mice immunized with an inactivated vaccine. In summary, the developed vaccine can elicit a multifaceted immune response and induce robust viral clearance in the URT, which makes it a potential vaccine for preventing disease and infection of SARS-CoV-2.