Researchers in the United States and South Africa report that the NVX-CoV2373 vaccine from Novavax has proved effective at preventing coronavirus disease (COVID-19) caused by the B.1.351 variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has recently emerged in South Africa.
In a phase 2a/b trial involving more than 4,000 participants in South Africa, a two-dose regimen of the vaccine was 60.1% effective at preventing COVID-19 predominantly caused by the B.1.351 variant among individuals who had not previously been infected with a previous strain of SARS-CoV-2.
Preliminary safety data also indicated an acceptable safety and reactogenicity profile. Local and systemic reactions were mainly mild to moderate and generally lasted less than 3 days.
However, among control participants who received placebo, evidence of prior infection with the presumptive original SARS-CoV-2 strain was not associated with protection against disease caused by the B.1.351 variant.
“This is the first report to provide evidence, in the setting of a controlled vaccine trial, that prior infection with first-wave prototype-like, pre-B.1.351 viruses did not reduce the risk of COVID-19 due to re-infection with B.1.351 variants among placebo recipients,” write the researchers.
The team – from Novavax, Inc., in Gaithersburg, Maryland and various institutions in South Africa – says the findings have significant public health implications for pandemic control strategies and the development and deployment of vaccines.
Vivek Shinde and colleagues advise that although the NVX-CoV2373 vaccine clearly induced cross-protection at clinically significant levels, these findings support the rapid development of vaccine formulations containing the B.1.351 variant.
A pre-print version of the research paper is available on the medRxiv* server, while the article undergoes peer review.
Recently merged variants threaten progress made with vaccination
The recent emergence of SARS-CoV-2 variants poses a threat to the progress made towards controlling the COVID-19 pandemic through vaccination.
In an ongoing randomized, placebo-controlled, phase 1/2 trial of healthy adults, a two-dose regimen of the NVX-CoV2373 vaccine administered 21 days apart was associated with neutralizing antibody responses four times higher than those induced by convalescent sera from moderate-to-severe COVID-19 cases.
However, recent reports on the SARS-C0V-2 variants that have recently emerged in the UK (B.1.1.7), Brazil (P.1), and South Africa (B.1.351) have shown that mutations in key antigenic sites of the virus may render naturally acquired or vaccine-derived immunity to the original strain less protective against variant strains.
What did the current study involve?
Shinde and colleagues have described the preliminary findings of a phase 2a/b trial involving 4,406 participants (mean age 32 years) who were randomly assigned to receive a two dose-regimen (administered 21 days apart) of either the NVX-CoV2373 vaccine or placebo.
Participants included healthy HIV-negative individuals and medically stable people living with HIV (PLWH). All of them lived in South Africa, while the predominant circulating SARS-CoV-2 strain was the B.1.351 variant.
The primary endpoints were safety and vaccine efficacy at 7 days or more following the second dose (after day 28) against symptomatic COVID-19 in previously uninfected participants (seronegative for SARS-CoV-2 at baseline).
A total of 4,387 participants received at least one injection of NVXACoV2373 (n=2,199) or placebo (n=2,188), with 4,332 participants receiving both injections.
What did the study find?
Approximately 30% of participants were seropositive for SARS-CoV-2 at baseline.
Among 2,684 participants who were seronegative at baseline (94% HIV-negative; 6% PLWH), 15 cases of symptomatic COVID-19 were observed in the vaccinated group after day 28, compared with 29 cases in the placebo group, corresponding to a vaccine efficacy of 49.4%.
All cases of the disease were mild to moderate, except for one severe case in the placebo group.
Among the HIV-negative participants, 11 cases of symptomatic COVID-19 were observed in the vaccinated group, compared with 27 in the placebo group, corresponding to a vaccine efficacy of 60.1%. Vaccine efficacy was unaffected by baseline SARS-CoV-2 serostatus in this group. The study was not powered to detect efficacy in the small PLWH cohort.
Of the 44 cases who met the primary efficacy endpoint criterion, whole genome sequence data were available for 41 (samples from 3 cases in the placebo group could not be sequenced). Of these cases, 38 (92.7%) were found to be caused by the B.1.351 variant.
In a post-hoc analysis, vaccine efficacy against the variant was 51.0% in HIV-negative, baseline seronegative participants and 43.0% in the combined HIV-negative and PLWH baseline seronegative population.
Interestingly, the incidence of symptomatic COVID-19 cases among placebo recipients was similar between baseline seronegative and baseline seropositive participants during the first 60 days of follow-up, at 5.3% versus 5.2%.
Evidence of cross-protection against an escape variant
“Although these findings require further confirmation, our observations suggest that vaccination with prototype-sequenced NVX-CoV2373 conferred cross-protection against an immunological escape variant, in stark contrast to naturally acquired immunity,” writes Shinde and colleagues.
The researchers say wild-type and pseudo-virus neutralization assays assessing the impact of the B.1.351 variant on the neutralizing capacity of NVX-CoV2373 vaccine-elicited antibodies are in progress.
“Nevertheless, this is the first study to provide definitive clinical evidence of cross-protection against antigenically drifted viruses,” they add.
“Although cross-protection was clearly present at clinically meaningful levels, our observations support the rapid development of vaccine formulations containing the B.1.351 variant,” concludes the team.
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.