COVID-19 vaccines prove their mettle against B.1.351 variant

Available COVID-19 vaccines remain highly protective against currently circulating SARS-CoV-2 variants of concern — including the South Africa B.1.351 strain — despite initial concerns of dented antibody neutralization activity, suggests growing evidence from real world and randomized studies.  

A single dose of the Janssen’s Ad26.COV2.S vaccine was 64 percent effective against moderate-to-severe COVID-19, 28 days after vaccination among 6,576 people in South Africa, where B.1.351 is the predominant circulating strain. Efficacy against severe-to-critical illness appeared to be even higher, at 81.7 percent. [N Engl J Med 2021;doi:10.1056/NEJMoa2101544]

These participants were a subset of an overall population of 43,783 participants in the large, multinational, phase III ENSEMBLE study. Among the 91 South African cases with sequencing data available, 86 (95 percent) were caused by the B.1.351 variant.

The corresponding figures among the South African participants were not far off in comparison with the overall population — at 66.1 percent and 85.4 percent for moderate-to-severe and severe-to-critical illness, respectively, 28 days after dosing.

Similarly, a separate phase III study on the Pfizer-BioNTech’s BNT162b2 mRNA vaccine — which included 800 participants from South Africa — showed that none of those who had been vaccinated developed COVID-19 compared with nine cases in the placebo arm. [https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-confirm-high-efficacy-and-no-serious. Accessed 25 May 2021]

This indicates that the antibody response induced by the BNT162b2 vaccine was highly robust — so much so that even when the response to B1.351 was lower than to the wild-type strain, it did not compromise its protective efficacy against the B1.351 variant.

Another vaccine in the pipeline, the Novavax’s NVX-CoV2373 protein-based vaccine, showed an efficacy of 49.4 percent against mild-to-moderate COVID-19 among 2,684 predominantly HIV-negative participants in South Africa. [N Engl J Med 2021;384:1899-1909]

When restricting the analysis to 94 percent of the participants who were HIV-negative, vaccine efficacy was 60.1 percent. Among those with sequencing data available, the efficacy against B.1.351 was 51.0 percent.

Real-world evidence

Real-world data from 385,853 people in Qatar showed that efficacy of the BNT162b2 vaccine was 89.5 percent against the B.1.1.7 variant and 75 percent against the B.1.351 variant. [N Engl J Med 2021;doi:10.1056/NEJMc2104974]

Importantly, vaccine efficacy against severe, critical, or fatal COVID-19 illness was high overall, at 97.4 percent, regardless of variants.

“The BNT162b2 vaccine was effective against infection and disease in the population of Qatar, despite the B.1.1.7 and B.1.351 variants being predominant within the country,” the researchers stated.

Almost half (44.5 percent) of COVID-19 cases in Qatar were caused by B.1.1.7 — the dominant strain early in the vaccination programme — and another 50 percent were caused by B.1.351, which became dominant in mid-March.

“[Although] vaccine effectiveness against the B.1.351 variant was approximately 20 percentage points lower than the effectiveness (>90 percent) reported in the clinical trial and in real-world conditions in Israel, … the reduced protection against infection with the B.1.351 variant did not seem to translate into poor protection against the most severe forms of infection (i.e., those resulting in hospitalization or death),” highlighted the Qatar investigators.

Variants, and more variants

These early data, according to the US White House chief medical advisor Dr Anthony Fauci, look promising, although the vaccine efficacy against other variants of concern such as the Brazil P.1 variant and the India B.1.617 variant remains unclear.

“It does not look like at this point — and this is subject to change — that [the B.1.617 variant] is any more problematic than B.1.351,” Fauci said during the opening keynote address at the ATS* virtual meeting.

In addition to a mutation at N501Y which increases the virus transmissibility, the B.1.351 variant also harbours the E484K mutation, which is known to reduce viral sensitivity to neutralization by monoclonal antibodies as well as convalescent and post-vaccination serum.

“The emergence of variant strains is arguably the greatest threat to control of the COVID-19 pandemic,” wrote Dr Kathleen Neuzil, University of Maryland School of Medicine, Baltimore, Maryland, US, in an editorial. “SARS-CoV-2 will continue to replicate in humans, mutations will continue to occur, and variants of concern will continue to emerge.” [N Engl J Med 2021;384:1952-1954]

“A coordinated global prevention-and control plan is the only way forward,” she highlighted. “From a public health perspective, limiting viral transmission through widespread use of vaccines, masking, social distancing, and other control measures will reduce new viral mutations.”

 

*ATS: American Thoracic Society