Rational design of an influenza-COVID-19 chimeric protective vaccine with HA-stalk and S-RBD

Emerg Microbes Infect. 2023 Dec;12(2):2231573. doi: 10.1080/22221751.2023.2231573.

Abstract

Highly contagious respiratory illnesses like influenza and COVID-19 pose serious risks to public health. A two-in-one vaccine would be ideal to avoid multiple vaccinations for these diseases. Here, we generated a chimeric receptor binding domain of the spike protein (S-RBD) and hemagglutinin (HA)-stalk-based vaccine for both SARS-CoV-2 and influenza viruses. The S-RBD from SARS-CoV-2 Delta was fused to the headless HA from H1N1 (H1Delta), creating a chimera that forms trimers in solution. The cryo-electron microscopy structure of the chimeric protein complexed with the RBD-targeting CB6 and the HA-stalk-targeting CR9114 antibodies shows that the trimeric protein is stable and accessible for neutralizing antibody binding. Immunization with the vaccine elicited high and long-lasting neutralizing antibodies and effectively protected mice against the challenges of lethal H1N1 or heterosubtypic H5N8, as well as the SARS-CoV-2 Delta or Omicron BA.2 variants. Overall, this study offers a two-in-one universal vaccine design to combat infections caused by both SARS-CoV-2 variants of concern and influenza viruses.

Keywords: Omicron; SARS-CoV-2; Universal vaccine; broadly neutralizing antibody; chimeric antigen; influenza; subunit vaccine.

MeSH terms

  • Animals
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • COVID-19* / prevention & control
  • Cryoelectron Microscopy
  • Hemagglutinins
  • Humans
  • Influenza A Virus, H1N1 Subtype* / genetics
  • Influenza Vaccines* / genetics
  • Influenza, Human*
  • Mice
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / genetics

Substances

  • Hemagglutinins
  • COVID-19 Vaccines
  • Antibodies, Viral
  • Influenza Vaccines
  • Antibodies, Neutralizing
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2

Supplementary concepts

  • SARS-CoV-2 variants

Grants and funding

This work was supported by National Key Research and Development Projects of the Ministry of Science and Technology of China: [Grant Number 2020YFA0907102, 2021YFC2301400, 2021YFC2301300); Strategic Priority Research Program of CAS: [Grant Number XDB29010202, XDB29040203]; CAS Project for Young Scientists in Basic Research: [Grant Number YSBR-010]; the National Natural Science Foundation of China: [Grant Number 82122040].