Efficacy of vaccines against the SARS-CoV-2 Delta variant

The coronavirus 19 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported in Wuhan, China in late 2019. Since then, COVID-19 has caused the deaths of more than 4.5 million people worldwide, along with social and economic disruption.

Study: Prediction of vaccine efficacy of the Delta variant. Image Credit: Fit Ztudio /

COVID-19 vaccines

In general, scientists around the world have widely accepted that the development of safe and efficient vaccines against SARS-CoV-2 will help to bring the world to its pre-pandemic normalcy. To this end, several different COVID-19 vaccines, many of which are based on new technology, have been developed and since approved for use in many countries around the world.

Despite the ground-breaking rate at which vaccines were developed, the emergence of mutated strains of SARS-CoV-2 have led to immune evasion and challenged the efficacy of the vaccines that were primarily developed against the prototype strain. In fact, the efficacy of the vaccines against the SARS-CoV-2 Delta variant, which is largely the dominant circulating strain worldwide, is still unknown.

The SARS-CoV-2 Delta variant has certain key mutations of L452R, P681R, and T478K that aids in its immune evasion against neutralization. The L452R mutation, for example, causes structural changes in the receptor-binding domain (RBD), which normally functions to increase the interaction between the spike (S) protein and the angiotensin-converting enzyme 2 (ACE2) receptor of the host cell. Comparatively, the T478K mutation reduces neutralizing potency of certain antibody lineages.

A new study published in the pre-print server medRxiv* uses statistical models to determine vaccine-specific efficacy against the various SARS-CoV-2 variants and clinical endpoints for the Delta variant and other variants of concerns (VoC), as defined by the World Health Organization.

About the study

The current study involved a widespread search from three peer-reviewed databases (PubMed, Web of Science, and Embase) and an open science platform (Europe PMC) to obtain studies on original analyses of COVID-19 vaccine efficacy against wild type and new variants.

This systemic research was also done to update the previously reported meta-analysis of in vitro neutralization titers of individuals who had been vaccinated against both the prototype strain and the new variants. These two datasets were combined to determine vaccine efficacy against the new strains.

Efficacy data against both symptomatic and severe infection for both the prototype and mutant strains were collected from a total of nine vaccines. Matching of the efficacy data to the neutralization data helped to predict the efficacy of six vaccines that included the BNT162b2, mRNA-1273, Gam-COVID-Vac, Ad26.COV2.S, ChAdOx1 nCoV-19, and NVX-CoV2373 vaccines.

Study findings

The results of the current study indicated that the predicted efficacy against the Delta variant is much lower than the prototype strains. The results also showed that the reduction in predicted efficacy is more for the adenovirus-vector vaccines as compared to the messenger ribonucleic acid (mRNA) vaccines.

The loss of predicted efficacy of the vaccines against the Delta variant was found to be less than that when these vaccines were assessed against the Beta variant. Additionally, the vaccine efficacy estimate was found to be lower than the Alpha and Gamma variants.

Phase 3 randomized controlled trials help to provide accurate data on efficacy among specific populations, whereas test-negative/cohort studies provided real-world insights on protection against different SARS-CoV-2 variants. However, since most vaccines were developed using prototype-virus-based clinical trials without sequencing, the efficacy of the majority of vaccines against the different SARS-CoV-2 variants is still unknown. Furthermore, most of the studies were performed before the emergence of the Delta strain; therefore, it is difficult to repeat these studies exactly how they were done before.

The use of an in vitro cross-neutralizing assay is effective and time-saving for determining the predicted efficacy of the vaccines.


Despite being able to provide valuable insights on the efficacy of vaccines against the SARS-CoV-2 mutant strains, the current study has certain limitations. Firstly, the prediction is based on the assumption that neutralizing antibodies are the only determinants of immune protection, while humoral and cellular immunity may also be important.

Secondly, the results are based on a previously established model and not by conducting studies in the real world. Thirdly, due to limited observed efficacy against infections, the study may overestimate the predicted efficacy of the vaccines.

“Finally, as the various variants continue to emerge worldwide, our data may serve to inform decisions towards resource allocation and planning of mitigation measures by public health decision-makers.”

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

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