COVID-19 Vaccine Development and Efficacy

In under two years since the emergence of SARS-CoV-2, multiple vaccine platforms have progressed from genomic sequencing to global deployment. mRNA vaccines, protein-based nanoparticle formulations and viral vectors have all demonstrated robust immunogenicity by inducing neutralising antibodies and T-cell responses against the spike glycoprotein. Rapid phase 3 trials provided clear measures of vaccine efficacy against symptomatic and severe disease, initially against ancestral strains and later against variants of concern including Alpha, Beta, Delta and Omicron. The integration of novel adjuvants has enhanced immunogenicity in protein constructs and enabled dose sparing. Heterologous booster regimens have been shown to broaden and heighten immune protection, especially against immune-evasive sub-lineages. Ongoing surveillance, real-world effectiveness studies and iterative vaccine design will be key to sustaining protection in diverse populations and low-resource settings.

Research from Nature Portfolio

Recent systematic comparisons across phase 3 trials have ranked mRNA-1273 and BNT162b2 platforms highest for preventing symptomatic COVID-19 in adults, while also confirming comparable protection in older age groups. Protein-based nanoparticle vaccines have proven effective as standalone regimens and as heterologous boosters. In experimental models of the Omicron BA.5 subvariant, prime-boost sequences involving protein-nanoparticle boosters elicited stronger neutralising titres and reduced viral replication compared with homologous mRNA or adenoviral regimens. Further work has characterised the neutralisation profiles of ancestral-sequence protein vaccines, showing that a third dose restores cross-reactive neutralising activity against Omicron BA.1 and BA.4/5 to levels on par with three-dose mRNA series.

COVID-19 Vaccine Development and Efficacy publication trend

The graph below shows the total number of articles in covid-19 vaccine development and efficacy across all publications each year (not limited to Nature Index journals).

Technical terms

Neutralising antibody: Antibody that binds to viral surface proteins to block entry into host cells and prevent infection.

Adjuvant: Substance added to a vaccine formulation to enhance or modulate the immune response to the antigen.

Protein nanoparticle vaccine: Vaccine comprising viral proteins self-assembled into nanoscale particles to mimic the structure of the virus and improve immunogenicity.

Homologous booster: Additional vaccine dose using the same vaccine platform as the initial series.

Heterologous booster: Booster dose employing a different vaccine platform or formulation from that used in the primary vaccination series.

References

1. Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant. New England Journal of Medicine (2021).
2. Comparing the clinical efficacy of COVID-19 vaccines: a systematic review and network meta-analysis. Scientific Reports (2021).
3. Different dose regimens of a SARS-CoV-2 recombinant spike protein vaccine (NVX-CoV2373) in younger and older adults: A phase 2 randomized placebo-controlled trial. PLOS Medicine (2021).
4. Safety and immunogenicity of an AS03-adjuvanted plant-based SARS-CoV-2 vaccine in Adults with and without Comorbidities. npj Vaccines (2022).
5. Novavax NVX-COV2373 triggers neutralization of Omicron sub-lineages. Scientific Reports (2023).
6. Immunogenicity of NVX-CoV2373 heterologous boost against SARS-CoV-2 variants. npj Vaccines (2023).
7. Immunogenicity and efficacy of vaccine boosters against SARS-CoV-2 Omicron subvariant BA.5 in male Syrian hamsters. Nature Communications (2023).