Exploration of the cross-immunity between SARS-CoV and SARS-CoV-2 in mice

Abstract

Aim: This study aimed to develop a universal vaccine that can effectively address future outbreaks of coronavirus infections. Materials & methods: We developed recombinant DNA vaccines and vaccinia vector vaccines specific for SARS-CoV and SARS-CoV-2 and evaluated them in BALB/c mice. Both cellular and humoral immune responses were analyzed. Results: Compared with those immunized with the SARS-CoV or SARS-CoV-2 vaccine alone, the cross-immune group exhibited a 21.2-fold increase in cellular immune response, an over 80-fold increase in binding antibodies and a 136.7-fold increase in neutralizing antibodies. The combination of recombinant DNA and vaccinia vaccines induced a stronger immune response than DNA vaccine immunization alone. Conclusion: This study demonstrated that cross-immunization with different coronaviruses can induce a broad immune response.

Plain language summary

Multiple outbreaks of infections caused by coronaviruses like SARS-CoV-2 have driven the need for a vaccine that can work against multiple types of coronaviruses. This study focused on two coronaviruses, SARS-CoV and SARS-CoV-2, to see if a vaccine could protect against both. We tested a vaccine containing both types of coronaviruses on mice and found that there was a strong immune response against both SARS-CoV and SARS-CoV-2. In fact, using a combination of the two vaccines was even more effective than using either one alone. These findings suggest that being vaccinated for both coronaviruses could provide broader protection against different types of coronaviruses and offer important information about how to develop vaccines that work against multiple viruses.

Summary points

• As the outbreaks of new viruses, particularly SARS-related viruses, become increasingly frequent, we try to develop a universal vaccine strategy to response to potential new viruses emergence.

• We chose mice with cross-immunity to SARS-CoV and SARS-CoV-2 in order to explore methods for inducing broad immune responses.

• Cross-immunization with SARS-CoV and SARS-CoV-2 can induce broader cellular immune response, binding antibodies and neutralizing antibodies than administering either of them alone.

• Combination of recombinant DNA and vaccinia vaccines induced a stronger immune response than DNA vaccine immunization alone.

• Sequential immunization with different vaccines could be a feasible vaccination strategy for future virus outbreaks.

Keywords: :

• cross immunity
• DNA vaccine
• prime boost
• SARS-CoV
• SARS-CoV-2
• sequential immunization
• universal vaccine
• vaccinia vector vaccine

Author contributions

Y Hao, Y Shao and Y Liu contributed to the study conception and design. Completion of the main experimental work, data collection and analysis were performed by Y Hao and S Wang. The pseudovirus assay was performed by L Ren. Animal experiments were conducted by Y Hao, X Shen and S Wang. The first draft of the manuscript was written by Y Hao. All authors read and approved the final manuscript.

Financial disclosure

This work was financially supported by the National Nature Science Foundation of China (U20A20362) and the Subject of National Major Special Projects of the 13th Five-Year Plan of China (2018ZX10731-101-001-008). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

This research was approved by the Institutional Animal Care and Use Committee (IACUC) of the China Center for Disease Control and Prevention (approval number: 2021-CCDC-IACUC-005).

Acknowledgments

The authors are grateful to the National Vaccine and Serum Institute for donating the smallpox vaccine as a vaccinia vector. The authors are also grateful to Jay Levy, the professor at University of California at San Francisco, USA, for his invaluable guidance throughout the manuscript writing. They also thank Editage (www.editage.cn) for English language editing.

Additional information

Funding

This work was financially supported by the National Nature Science Foundation of China (U20A20362) and the Subject of National Major Special Projects of the 13th Five-Year Plan of China (2018ZX10731-101-001-008).