SARS-CoV-2 Vaccine Development Strategies

Since early 2020, unprecedented efforts have been devoted to design, test and deploy vaccines that can safely elicit robust and durable immunity against SARS-CoV-2. Platform technologies range from traditional inactivated and protein subunit vaccines to novel nucleic acid approaches, notably messenger RNA formulations encoding the viral spike glycoprotein. Viral vector systems, including adenovirus- and poxvirus-based constructs, have been engineered to present one or more antigenic targets, while live attenuated and replicating bacterial vectors are under investigation for broader immunogenic breadth. Strategies have also explored multi-antigenic designs that incorporate structural proteins such as nucleocapsid alongside spike to improve both mucosal and systemic immune responses. Critical to these developments are the selection of immunostimulatory adjuvants, optimisation of antigen conformations to focus neutralising antibody responses, and iterative adaptation to emerging variants of concern. Collectively, these approaches aim to achieve high efficacy, cross-protection against divergent strains and logistical feasibility for global distribution.

Research from Nature Portfolio

Recent studies have demonstrated the rapid assembly of a synthetic DNA-based vaccine platform using a modified vaccinia Ankara vector encoding both spike and nucleocapsid antigens. In preclinical models, a single regimen of this multi-antigenic construct elicited strong neutralising antibody titres and multifunctional T-cell responses. The modular design enabled swift production of new variants and underscored the value of co-presenting multiple antigens to broaden protective immunity, offering a blueprint for next-generation poxvirus-vectored vaccines against SARS-CoV-2 and related coronaviruses.

SARS-CoV-2 Vaccine Development Strategies publication trend

The graph below shows the total number of articles in sars-cov-2 vaccine development strategies across all publications each year (not limited to Nature Index journals).

Technical terms

Modified vaccinia Ankara (MVA): A highly attenuated poxvirus platform engineered to deliver vaccine antigens without causing disease.

Spike protein: A trimeric surface glycoprotein of SARS-CoV-2 responsible for binding to the host ACE2 receptor and mediating viral entry.

Nucleocapsid protein: An internal structural protein that packages viral RNA and can elicit robust T-cell responses.

Adjuvant: A component that enhances the immune response to a vaccine antigen, improving magnitude or duration of immunity.

Neutralising antibody: An antibody that directly inhibits viral attachment or fusion, thereby preventing host cell infection.

Viral vector: A virus modified to carry and express genetic material encoding one or more vaccine antigens in the host.

References

1. Development of a multi-antigenic SARS-CoV-2 vaccine candidate using a synthetic poxvirus platform. Nature Communications (2020).
2. Synthetic multiantigen MVA vaccine COH04S1 and variant-specific derivatives protect Syrian hamsters from SARS-CoV-2 Omicron subvariants. npj Vaccines (2023).
3. Combining spike- and nucleocapsid-based vaccines improves distal control of SARS-CoV-2. Cell Reports (2021).
4. A single dose, BCG-adjuvanted COVID-19 vaccine provides sterilising immunity against SARS-CoV-2 infection. npj Vaccines (2021).