How effective are COVID-19 vaccines against SARS-CoV-2 variants of concern?

By Colin Lightfoot, M.Sc. Infection and ImmunitySep 29 2021

As of 29 September 2021, there have been more than 232 million cases and 4.76 million deaths recorded worldwide as a result of coronavirus 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).  A number of vaccines have been developed to cope with this pandemic, and they have proven highly effective in observational and randomized trials (RCTs). The key antigenic target for most current vaccines is the SARS-CoV-2 spike protein.

From the expanding proportion of cases in England in late 2020, the B.1.1.7 (Alpha) variant was first identified from genomic sequencing of samples obtained from COVID-19 patients, the B.1.351 (Beta) variant was then identified in South Africa, the P.1 (Gamma) in Brazil and the B.1.617.2 (Delta) variant in India.

Due to the association with increased transmission, more severe disease outcomes, a reduction in neutralization antibodies generated from vaccines and previous infection, and reduced effectiveness of treatments, the Alpha, Beta, Gamma, and Delta variants have been classified as variants of concern (VOC).

If the virulence or transmissibility of VOC increases, then the importance of vaccination programs and efficient public health measures will also increase. It was essential to generate evidence of vaccine effectiveness of COVID-19 vaccines against VOC.

The authors from this paper performed a systematic review and meta-analysis evaluating vaccine effectiveness from RCTs and observational studies.

A preprint version of this study, which is yet to undergo peer review, is available on the medRxiv* preprint server.

Study: Effectiveness of COVID-19 vaccines against SARS-CoV-2 variants of concern: a systematic review and meta-analysis. Image Credit: NIAID

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

The effectiveness of vaccines against the Alpha variant

To determine the efficacy of vaccines against the alpha variant, the authors analyzed 2 RCTs, 5 cohort studies, and 11 case-control studies. A total of 4 COVID-19 vaccines were included for the analysis (mRNA-1273, NVX-CoV2373, ChAdOx1, and BNT162b2).

The total vaccine effectiveness of full vaccination against the Alpha variant was 88.3%. Analysis of subgroups by study design displayed vaccine effectiveness to be 79.4% in two RCTs, 88.3% in 5 cohort studies, and 88.7%  in 10 case-control studies.

Vaccine type subgroup analysis showed vaccine effectiveness to be 90.9% for mRNA vaccinations in 15 study groups, 73.8%  in 5 study groups with non-replicating vector vaccines, 86.3% in 1 study group for protein subunit vaccines, and 82.0% for the combination of the BNT162b2 and ChAdOx1 vaccines in 1 study group. Furthermore, they noted that, on average, mRNA vaccines performed better than non-mRNA vaccines.

The total vaccine effectiveness of a partial vaccination against the Alpha variant was 59.0%. Analysis of subgroups by study design showed vaccine effectiveness to be 53.3% in 4 cohort studies and 60.6% in 10 case-control studies. In a partial vaccination, mRNA vaccines also performed better.

Forest plot showing vaccine effectiveness of COVID-19 vaccines against Alpah variant. Abbreviations: VE, vaccine effectiveness; CI, confidence interval; RCT, randomized controlled trial.

The effectiveness of vaccines against the Beta and Gamma variants

To evaluate vaccine effectiveness against the Beta variant, 4 RCTs, 1 cohort study, and 4 case-control studies were analyzed. To assess vaccine effectiveness against the Gamma variant, 1 cohort study and 3 case-control studies were analyzed.

The total vaccine effectiveness against the Beta variant was 73.2. Analysis of subgroups by study design displayed vaccine effectiveness to be 70.2% in the 4 RCTs, 80.2% in the 4 case-control studies, and 49.0% in the cohort study. Analysis of vaccine-type subgroups revealed for mRNA vaccines in 6 studies, the vaccine effectiveness was 80.3%, for non-replicating vector vaccines in 2 studies, the vaccine effectiveness was 44.9%, and for protein subunit vaccines in 1 study, the vaccine effectiveness was 51.1%.

The total vaccine effectiveness against the gamma variant was 47.5% in 4 study groups, and with a partial dose of the vaccine, the effectiveness was 40.6%  in 2 study groups. When Beta and Gamma variants were grouped together, total vaccine effectiveness was 70.7%. The most effective vaccines against both these variants were the mRNA.

Forest plot showing vaccine effectiveness of COVID-19 vaccines against Beta/Gamma variants. Abbreviations: VE, vaccine effectiveness; CI, confidence interval; RCT, randomized controlled trial.

The effectiveness of vaccines against the Delta variant

To determine the efficacy of the vaccines against the delta variant, the authors analyzed one RCT, 4 cohort studies, and 7 case-control studies. The total vaccine effectiveness against the Delta variant was 71.6%.

Analysis of subgroups by study design showed that vaccine effectiveness in the RCT was 65.2%, 74.8% in the 7 case-control studies, and 66.2% in the 4 cohort studies. Analysis of vaccine effectiveness by vaccine type showed that mRNA vaccines were 75.6% in 11 study groups, non-replicating vector vaccine effectiveness was 64.4% in 4 study groups, and the vaccine effectiveness of inactivated vaccines was 62.5% in 2 study groups.

Analysis of vaccine effectiveness against the Delta variant with a partial dose of the vaccines was 52.6%. Analysis of vaccine effectiveness by study design subgroups showed it to be 59.5% in the cohort study and 49.3% in the 7 case-control studies. The most effective vaccine type against this variant was the mRNA-based vaccines.

Forest plot showing vaccine effectiveness of COVID-19 vaccines against Delta variant. Abbreviations: VE, vaccine effectiveness; CI, confidence interval; RCT, randomized controlled trial.

Implications

The data analyzed for this systematic review and meta-analysis shows that full vaccination with COVID-19 vaccines is highly effective against the Alpha variant but less effective against the Beta, Gamma, and Delta variants. Furthermore, only a partial dose of any vaccine is shown to be much less effective against all the variants. Therefore, the data suggest that full vaccination should be recommended against all VOCs.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources