Beta strain-containing bivalent vaccine protects against various SARS-CoV-2 variants

A Beta variant-containing vaccine conferred protection against different SARS-CoV-2 variants, with an acceptable safety profile in adults <60 years, a phase III trial has shown.

“[This] bivalent recombinant protein vaccine contained stabilized SARS-CoV-2 prefusion S proteins from both the ancestral Wuhan-Hu-1 (D614) and the B.1.351 variant, with the GSK AS03 adjuvant system,” said the researchers. “Our Beta strain-containing vaccine confers protection against Omicron BA.1 and BA.2 variants that are not a component of the vaccine, thus providing clinical evidence that cross-protection might be conferred without a variant-chasing approach.”

About 13K individuals were randomized 1:1 to two 0.5-mL injections of the vaccine (5 μg ancestral, 5 μg Beta variant spike protein, with AS03 adjuvant) or placebo 21 days apart. A total of 12,924 participants received at least one injection (mean age 36.1 years, 58 percent male, 75 percent SARS-CoV-2 non-naïve). Median follow-up duration was 85 days after dose 1 and 58 days after dose 2. [Lancet Respir Med 2023;doi:10.1016/S2213-2600(23)00263-1]

In the modified full analysis set (n=11,416), 121 symptomatic COVID-19 cases were reported at least 14 days after dose 2, with more cases in the placebo vs the vaccine arm (n=89 vs 32). This translated to an overall vaccine efficacy of 64.7 percent (95 percent confidence interval [CI], 46.6–77.2).

“The primary objective was met in all participants, demonstrating efficacy against symptomatic COVID-19 higher than 50 percent, with a lower bound of the 95 percent CI higher than 30 percent,” the researchers noted.

Reactogenicity

In the reactogenicity subset (n=4,851), less than half of vaccine and placebo recipients reported injection-site reactions (47 percent vs 27 percent) and systemic reactions (46 percent vs 34 percent). “These rates might indicate potentially less reactogenicity compared with mRNA-based licensed vaccines … although these vaccines have not been evaluated together in the context of a single trial,” said the researchers.

There were low rates of adverse events (AEs) of special interest, serious AEs, and deaths in both arms (<1 percent). No AE of special interest, serious AE, or death was considered treatment related. There were no reported cases of myocarditis, pericarditis, and thrombosis with thrombocytopenia syndrome, which have been previously reported with other vaccines.

Extends options for cross-protection

First-generation COVID-19 vaccines have been shown to be less effective against new emergent SARS-CoV-2 variants of concern, including Omicron. [Lancet 2021;397:1351-1362; N Engl J Med 2021;384:1899-1909; JAMA Netw Open 2022;5:e2232760; N Engl J Med 2022;386:494-496; N Engl J Med 2023; 388:89-91] There is also the issue of waning immunity associated with the primary series of prototype vaccines. [N Engl J Med 2022;386:1532-1546; Am J Epidemiol 2023;192:895-907]

The findings showed the efficacy of two doses of a Beta variant-containing vaccine against Omicron as a primary series. “The data provide clinical evidence for a vaccination strategy to develop vaccines with an antigen from a non-predominant strain to confer cross-protection against newly emergent variants,” said the researchers.

“[T]he addition of new vaccines to the current armamentarium will extend options to facilitate protection across different regions, healthcare settings, and populations in the context of the ongoing pandemic, regardless of previous infection status, and with the threat of rapidly evolving SARS-CoV-2 strains,” they continued.

“[W]e should also consider the possibility that many people could be developing hybrid immunity to SARS-CoV-2, whereby immunity is formed by the combination of vaccination and infection,” the researchers noted. “Although data on hybrid immunity are currently scarce, the consensus opinion is that hybrid immunity confers greater protection than that obtained from either infection or vaccination alone.”

Study limitations include the small population of at-risk individuals (ie, older adults) and few COVID-19 hospitalizations and severe COVID-19 cases. “[W]e will continue to monitor and report data on moderate and severe COVID-19 and on hospital admissions due to COVID-19. The short follow-up duration also precluded any firm conclusions on the durability of the vaccine’s protection and long-term safety, which we will also continue to monitor,” they said.