Three vaccines show promise against COVID variants

COVID-19 vaccine being drawn into a syringe
COVID-19 vaccine being drawn into a syringe

Governor Tom Wolf / Flickr cc

Data from three trials posted yesterday show efficacy of the Novavax and Pfizer COVID-19 vaccines and good immune response of the Moderna vaccine against different SARS-CoV-2 variants of concern.

Novavax versus B1351

Two of the studies appeared in the New England Journal of Medicine (NEJM), the first of which describes a phase 2a-b clinical trial at 16 sites in South Africa from Aug 17 to Nov 25, 2020, on the efficacy of the Novavax COVID-19 vaccine against the B1351 variant first identified in South Africa, where virus transmission is ongoing.

Led by scientists from Novavax, the study involved randomly assigning HIV-negative participants aged 18 to 84 years and medically stable HIV-positive participants aged 18 to 64 years in a 1:1 ratio to receive two doses of either the Novavax vaccine or a placebo 21 days apart.

Roughly 30% of the 4,387 participants who received at least one dose of vaccine or placebo tested positive for COVID-19 at baseline. The vaccine group was made up of 2,199 participants, while 2,188 were in the placebo group.

Of the 2,684 initially uninfected participants (94% HIV-negative), 15 in the vaccine group and 29 in the placebo group later tested positive for coronavirus, for a vaccine efficacy of 49.4% (95% confidence interval [CI], 6.1% to 72.8%). Vaccine efficacy in HIV-negative participants was 60.1% (95% CI, 19.9% to 80.1%). The trial wasn't powered to determine efficacy in the small HIV-positive group.

Of the 41 virus isolates that were sequenced, 92.7% were B1351. Among HIV-negative participants, post hoc vaccine efficacy against B1351 was 51.0% (95% CI, -0.6% to 76.2%). More local and systemic adverse reactions occurred in the vaccine group than in the placebo group, and serious adverse events were rare in both.

"We have found that a prototype-sequenced NVX-CoV2373 [Novavax] vaccine was efficacious and induced notable cross-protection during a pandemic with a dominant circulation of the B.1.351 variant," the researchers wrote.

The authors noted that previous infection with a non-B1351 SARS-CoV-2 strain did not appear protective against B1351 in the first 2 months of follow-up but said that future research may help determine whether previous infection with the original SARS-CoV-2 strain alters the severity of infections with variants.

Mean participant age was 32 years, 57% were men, 95.3% were Black, 20% were obese, 5.6% had high blood pressure, and 1.6% had type 2 diabetes.

Pfizer against B1351, B117

In the second NEJM study, researchers from Weill Cornell Medicine and Hamad Medical Corp. in Qatar used national COVID-19 data to analyze the efficacy of the Pfizer/BioNTech COVID-19 vaccine against B1351 and B117, which was first observed in the United Kingdom.

As of Mar 31, 385,853 people in Qatar had received at least one dose of the vaccine, and 265,410 had received two doses. After Mar 7, almost all COVID-19 cases in Qatar were caused by B1351 or B117. 

Estimated Pfizer vaccine efficacy against B117 was 89.5% (95% CI, 85.9% to 92.3%) at least 14 days after the second dose, while efficacy against B1351 was 75.0% (95% CI, 70.5% to 78.9%). Efficacy against severe outcomes caused by any SARS-CoV-2 variant was 97.4% (95% CI, 92.2% to 99.5%).

When the researchers used a cohort study design to compare the incidence of infection in vaccinated people with that of an antibody-negative national cohort, vaccine efficacy against B117 was estimated at 87% (95% CI, 81.8% to 90.7%), and efficacy against B1351 was 72.1% (95% CI, 66.4% to 76.8%).

The authors observed that the vaccine was effective against the variants but that efficacy against B1351 was about 20 percentage points lower than that reported in a December 2020 Pfizer vaccine efficacy trial and in real-world studies in Israel and the United States. Also, 6,689 people in Qatar who had received one dose of the vaccine and 1,616 who had received two doses had breakthrough infections as of Mar 31; five people died of their infections after the first dose, and two died after the second.

"Nevertheless, 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), which was robust, at greater than 90%," the researchers concluded.

Coordinated global plan needed

In a commentary on both NEJM studies in the same journal, Kathleen Neuzil, MD, MPH, of the University of Maryland School of Medicine in Baltimore, said that trials of vaccines against currently circulating variants and those that have yet to emerge will become more difficult as randomized, controlled trials wane after broad vaccine availability.

"A global scientific agenda that encompasses extensive genomic surveillance, detailed 'correlate of protection' evaluations, and robust postintroduction surveillance and sequencing is necessary to measure the effect of new and current vaccines against SARS-CoV-2 variants," she wrote.

Neuzil called the emergence of variants the biggest threat to control of the pandemic. "A coordinated global prevention-and-control plan is the only way forward," she said. "Global investments in vaccine science and technology must be accompanied by investments in public health, genomic and disease surveillance, and programmatic immunization infrastructure to mitigate the effects of COVID-19 and future pandemics."

Moderna versus B1351, P1

In a press release, Moderna released preliminary data from its ongoing phase 2 clinical trial demonstrating that a single dose of its COVID-19 vaccine, when given as a booster to people who had completed their two-dose regimens, increased concentrations of neutralizing antibodies against SARS-CoV-2, B1351, and the P1 variant first seen in Brazil.

A strain-matched vaccine booster achieved higher antibody concentrations against B1351 than a booster with the original vaccine 15 days later. The trial is evaluating three types of booster vaccines: one based on B1351, a multistrain version, and its original vaccine.

The researchers found that 6 to 8 months after receiving two doses of the original vaccine against wild-type SARS-CoV-2, antibody levels against that strain were still high (37 of 40 participants had detectable antibody levels). But antibody concentrations against B1351 and P1 were significantly lower, with roughly half of participants having undetectable levels.

Participants given a booster dose 2 weeks after receiving the second dose showed antibody concentrations comparable to or higher than previously documented peak levels against the wild-type strain after two doses. The relative decrease in antibody levels between the B1351 and wild-type virus improved after the multistrain booster, falling from a 7.7-fold difference to 2.6-fold, which the researchers said suggests "a potentially more balanced immune response against the tested variants."

The boosters were generally well-tolerated and similar to those that occur after a second dose of the vaccine. Most adverse effects were mild or moderate, and no severe adverse events were reported. The multistrain booster was associated with fewer adverse events than the original vaccine.

Moderna Chief Executive Officer Stephane Bancel said that the company is encouraged by the findings. "The strong and rapid boost in titers to levels above primary vaccination also clearly demonstrates the ability of mRNA-1273 [original Moderna vaccine] to induce immune memory," he said in the release.

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