Variable vaccine efficacy against CoV-2 variants

 

The mRNA vaccines used to prevent COVID-19 appear to be highly effective against variants of concern, in contrast to the reduced efficacy seen with other vaccine technologies.

A national surveillance study in Israel reported that the efficacy of the Pfizer-BioNTech vaccine in real-world use 7 days after full vaccination (two doses) was 98.0% for symptomatic COVID-19, and 98.2% for severe/critical COVID (Haas et al. Lancet 2021; epublished 5 May 2021; www.thelancet.com/action/showPdf?pii=S0140-6736%2821%2900947-8). The estimated prevalence of the UK variant (B.1.1.7) at the time of the study was 94.5% of samples, indicating that efficacy against the variant was comparable to what has been reported against the pandemic strain (D614G variant). The UK variant has been associated with a higher risk of mortality (hazard ratio 1.67) (Grint et al. medRxiv, 10 March 2021; www.medrxiv.org/content/10.1101/2021.03.04.21252528v2.full.pdf). In the Israeli study, the estimated vaccine efficacy for the endpoint of COVID-related mortality was 96.6%. Efficacy against the South Africa (B.1.351) variant could not be estimated due to the small number of cases.

A separate study in Qatar estimated that the efficacy of the Pfizer-BioNTech vaccine against the UK and South Africa variants was 89.5% and 75.0%, respectively (Abu-Raddad et al. N Engl J Med 2021; epublished 5 May 2021. https://www.nejm.org/doi/10.1056/NEJMc2104974). The effectiveness against both variants with respect to severe/critical/fatal COVID-19 was 97.4%.

In contrast, vaccines that use other technologies appear to be substantially less effective – or ineffective – against variants of concern. For the AstraZeneca vaccine, a post-hoc analysis of UK data reported efficacy for symptomatic COVID-19 against the B.1.1.7 variant was 66.7% after two standard doses (Emary et al. Lancet 2021;397:1351-1362; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009612/). However, a separate study found that the AstraZeneca vaccine was not effective against the South Africa variant (Madhi et al. N Engl J Med 2021; epublished 16 March 2021. www.nejm.org/doi/full/10.1056/NEJMoa2102214). The randomized double-blind study (N=2026) reported that vaccine efficacy against the B.1.351 variant was 10.4%.

In the phase II South African trial of the Novavax spike protein/adjuvant vaccine, the overall efficacy against symptomatic COVID-19 was 49.4%; in the HIV-negative subgroup, efficacy was 60.1% (Shinde et al. N Engl J Med 2021; epublished 5 May 2021;  www.nejm.org/doi/full/10.1056/NEJMoa2103055). The estimated efficacy against the B.1.351 variant was 51.0% in the HIV-negative group after two doses. According to unpublished data from the interim analysis of the phase III trial, vaccine efficacy was 95.6% against pre-variant strains, and 85.6% against the UK strain (https://ir.novavax.com/news-releases/news-release-details/novavax-covid-19-vaccine-demonstrates-893-efficacy-uk-phase-3).

Some added protection may be obtained from a third vaccine dose, according to the results of the first posted study on booster injections. Subjects in the phase II and III studies of the Moderna mRNA-1273 vaccine were eligible for a booster dose administered 5.9-7.5 months after the second inoculation. The booster was either the mRNA-1273 vaccine or a retooled version encoding the S protein from the B.1.351 variant (mRNA-1273.351) (a multivalent vaccine, mRNA-1273.211, is also in development by Moderna). Both vaccines induced higher neutralizing antibody titres against the pandemic strain and the B1.351 and P.1 (Brazil) variants, indicating additional efficacy may be gained with a booster injection. The antibody response to the pandemic strain was higher with the original vaccine booster; response to the B.1.351 strain was higher with the novel mRNA-1273.351 vaccine. The study is ongoing.

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