A two-adjuvant multiantigen candidate vaccine induces superior protective immune responses against SARS-CoV-2 challenge

Cell Rep. 2021 Dec 14;37(11):110112. doi: 10.1016/j.celrep.2021.110112. Epub 2021 Nov 24.

Abstract

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.

Keywords: SARS-CoV-2; SFL(mut); cGAMP; flagellin; mucosal immunity; nucleocapsid; protective efficacy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Vaccine
  • Administration, Intranasal
  • Angiotensin-Converting Enzyme 2 / immunology
  • Angiotensin-Converting Enzyme 2 / metabolism
  • Animals
  • Antibodies, Viral / immunology
  • Antigens / immunology
  • COVID-19 / immunology
  • COVID-19 / prevention & control
  • COVID-19 Vaccines / genetics
  • COVID-19 Vaccines / immunology*
  • Chlorocebus aethiops
  • Combined Modality Therapy / methods*
  • Coronavirus Nucleocapsid Proteins / immunology
  • Female
  • Flagellin / immunology
  • HEK293 Cells
  • Humans
  • Immunity / immunology
  • Immunity / physiology
  • Immunity, Humoral / immunology
  • Immunization
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nucleotides, Cyclic / immunology
  • Phosphoproteins / immunology
  • SARS-CoV-2 / immunology*
  • SARS-CoV-2 / pathogenicity
  • Spike Glycoprotein, Coronavirus / immunology
  • Vaccination
  • Vero Cells

Substances

  • Adjuvants, Vaccine
  • Antibodies, Viral
  • Antigens
  • COVID-19 Vaccines
  • Coronavirus Nucleocapsid Proteins
  • Nucleotides, Cyclic
  • Phosphoproteins
  • Spike Glycoprotein, Coronavirus
  • cyclic guanosine monophosphate-adenosine monophosphate
  • nucleocapsid phosphoprotein, SARS-CoV-2
  • spike protein, SARS-CoV-2
  • Flagellin
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2