Infectious Disease

COVID-19 vaccine manufacturers release positive data on boosters

December 22, 2022

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Bancel and Das are employed by Moderna. Bourla is employed by Pfizer. Fauci reports no relevant financial disclosures. Glenn is employed by Novavax. Sahin is employed by BioNTech.


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The manufacturers of the COVID-19 vaccines authorized for use as additional booster shots in the United States all released positive clinical trial data on their retooled shots ahead of the start of the holiday season.

“We’re hoping that a combination of people who’ve been infected and boosted and vaccinated — or people who’ve been vaccinated and boosted and not infected — that there’s enough community protection that we’re not going to see a repeat of what we saw last year at this time,” National Institute of Allergy and Infectious Diseases Director Anthony S. Fauci, MD, said during a White House press briefing.

Bivalent COVID-19 booster graphic

Source: CDC

Anthony S. Fauci, MD
Anthony S. Fauci

All the data are from company-run trials.

Moderna tests two boosters

Moderna said data from a phase 2/3 trial showed that its bivalent COVID-19 booster shot elicited a higher antibody response against SARS-CoV-2 omicron subvariants than its original vaccine.

The booster, mRNA-1273.222, targets the wild-type vaccine and the omicron BA.4 and BA.5 subvariants and is one of two boosters Moderna has been testing against its original vaccine. Both mRNA-1273.222 and the company’s other booster vaccine, mRNA-1273.214 — which is aimed at the BA.1 subvariant — outperformed the original vaccine, according to a press release.

“We are pleased to see that both of our bivalent booster vaccine candidates offer superior protection against omicron BA.4/BA.5 variants compared to our original booster, which is encouraging given that COVID-19 remains a leading cause of hospitalization and death globally,” Moderna CEO Stéphane Bancel, MSc, MBA, said in the release.

In 511 previously vaccinated and boosted study participants aged 19 to 89 years, Moderna reported that the mRNA-1273.222 booster elicited a superior neutralizing antibody response against the BA.4 and BA.5 subvariants compared with a booster dose of the company’s original vaccine.

Study participants received Moderna’s original COVID-19 vaccine as a booster shot about 4 1/2 months after initial vaccination and the updated booster, mRNA-1273.222, about 9 1/2 months after initial vaccination. Although pre-booster titer levels were similar between the groups, the updated mRNA-1273.222 bivalent booster triggered a 15.1-fold increase in titer levels. Participants without a previous SARS-CoV-2 infection saw a 26.4-fold increase in titer levels and participants who had a previous infection saw a 9.8-fold increase in titer levels.

Moderna also reported that an exploratory analysis of 40 participants using research assays demonstrated “robust neutralizing activity” against BQ.1.1, though the response was about fivefold lower than the booster’s effects against BA.4 and BA.5.

Data published Oct. 6 in The New England Journal of Medicine also showed the mRNA-1273.214 booster triggered a stronger antibody response against BA.1, BA.4 and BA.5 than Moderna’s original shot.

“Responding quickly and effectively to emerging COVID-19 variants is one of the largest challenges facing the global community. This bivalent model provides a framework that may allow scientists to develop safe, effective and tailored vaccines more efficiently,” Rituparna Das, MD, Moderna’s vice president for clinical development of COVID-19 vaccines, said in a press release at the time.

Modern’s mRNA-1273.222 vaccine is authorized for use in people aged as young as 6 years.

At the time the new data were released, nearly three-quarters of new COVID-19 infections in the United States were caused by BA.5, BQ.1.1 and BQ.1, according to CDC. As of Nov. 24, only 12.1% of people aged 5 years or older received a bivalent booster dose, according to the CDC.

Bancel noted the antibody response garnered by the new boosters against BQ.1.1 in assays and said the new data confirm “that updated vaccines have the potential to offer protection as the virus continues to evolve rapidly to escape our immunity.”

Pfizer shot protects against emerging variants

Pfizer and BioNTech announced that their bivalent COVID-19 booster, which also targets the original strain of SARS-CoV-2 and the omicron BA.4 and BA.5 sublineages, elicited a stronger immune responses than their original vaccine in a phase 2/3 trial.

Adults aged 18 to 55 years experienced a 9.5-fold increase in neutralizing antibody titers against the omicron sublineages compared with pre-booster levels, and people aged older than 55 years saw a 13.2-fold rise, according to data reported in a press release.

In adults aged older than 55 years, neutralizing antibodies were fourfold higher after receiving the bivalent booster compared with original vaccine.

Pfizer chairman and chief executive officer Albert Bourla, DVM, PhD, said in the press release that the updated data “provide confidence in the adaptability of our [messenger RNA] platform and our ability to rapidly update the vaccine to match the most prevalent strains.”

“These data demonstrate that our BA.4/BA.5-adapted bivalent vaccine works as conceptually planned in providing strong protection against the omicron BA.4 and BA.5 sublineages,” Ugur Sahin, MD, CEO and co-founder of BioNTech, said in the release.

The results are from a phase 2/3 clinical trial of the bivalent booster that included 114 people who were tested 30 days after receiving either the bivalent booster or a booster dose of the original vaccine. Participants who received the bivalent vaccine had received a booster 10 to 11 months earlier, and those administered the original vaccine had received a booster about 7 months earlier.

Among the 38 participants aged 18 to 55 years, the geometric mean titer (GMT) against the omicron sublineages was 606 — a 9.5-fold rise over pre-booster levels. Among the 36 participants aged 55 years or older, the GMT was 896 — a 13.2-fold rise over their pre-booster levels.

Among 40 participants aged 55 years or older who received a booster of the original vaccine, the GMT was 236 — which is a 2.9-fold rise, meaning the neutralizing antibody titers were about fourfold higher for the bivalent booster over the original vaccine in this age group.

“As we head into the holiday season, we hope these updated data will encourage people to seek out a COVID-19 bivalent booster as soon as they are eligible in order to maintain high levels of protection against the widely circulating omicron BA.4 and BA.5 sublineages,” Bourla said.

The companies also announced new data showing that their bivalent COVID-19 booster vaccine elicited a stronger response specifically against the omicron BQ.1.1 sublineage than the original vaccine in people aged 55 years and older.

The results were from an analysis of the immune response induced by the bivalent shot against newer omicron sublineages, including BA.4.6, BA.2.75.2 and XBB.1, as well as BQ.1.1, which had doubled in prevalence in the weeks leading up to the announcement to account for around a quarter of cases in the U.S., according to the CDC’s COVID Data Tracker.

The new data, which were gathered 1 month after participants were given either a fourth dose of the omicron BA.4/BA.5-adapted vaccine or the original vaccine, showed that the bivalent booster generated a greater increase in neutralizing antibodies against emerging omicron sublineages than the original.

Specifically, the data showed that neutralizing antibodies against BA.4.6, BA.2.75.2, BQ.1.1 and XBB.1 increased by 11.1-fold (95% CI, 7.1-17.3), 6.7-fold (95% CI, 4.4-10.2), 8.7-fold (95% CI, 5.7-13.3), and 4.8-fold (95% CI, 3.3-6.9), respectively, among people given the adapted booster, compared with increases of 2.3-fold (95% CI, 1.9-2.8), 2.1-fold (95% CI, 1.7-2.5), 1.8-fold, (95% CI, 1.6-2.2), and 1.5-fold (95% CI, 1.3-1.8), respectively, following a booster dose of the companies’ original COVID-19 vaccine.

Based on these findings, the companies said the omicron BA.4/BA.5-adapted bivalent booster, which has been authorized for emergency use for people aged 5 years and older, could provide improved protection against COVID-19 due to omicron BA.4 and BA.5 sublineages as well as new sublineages that continue to increase in prevalence.

Two Novavax shots perform well

Novavax said that its omicron subvariant vaccine candidate and original COVID-19 vaccine both performed well in a phase 3 trial.

The trial showed no benefit from a bivalent shot combining the two vaccines, suggesting that a bivalent booster is not needed because its vaccine can be updated, when necessary, the company said.

Used as a fourth shot, Novavax’s original vaccine induced “a broad immune response” against the original strain of SARS-CoV-2, as well as the omicron BA.1 and BA.5 sublineages, the company said. Neutralizing responses were even greater among participants who received the BA.1 booster as a fourth shot compared with the original vaccine.

“[These] results show that use of our [original] vaccine as a booster induces cross-reactive responses to a broad range of variants with the potential to protect against future strains,” Gregory M. Glenn, MD, president of research and development at Novavax, said in a press release, adding that the Novavax vaccine “presents a potential strategy to protect against COVID-19 now and into the future.”

The data were from 273 participants who received a booster dose of the original vaccine, 279 who received a BA.1 booster vaccine candidate and 277 who received a bivalent booster dose composed of the original vaccine and the BA.1 candidate.

Although all three groups showed similar immunoglobulin G antibody responses against the wild-type virus and BA.1 variant, there was not a significant difference in efficacy against the BA.5 variant between the original Novavax vaccine, the BA.1 candidate or the bivalent vaccine, the company said.

When comparing neutralizing antibody responses among each of the three vaccine groups, the BA.1 booster vaccine induced a neutralizing response that was 1.6 times greater than the original vaccine among people who were not previously infected.

All three vaccine formulations were well tolerated, Novavax said, with the most common side effects among participants being pain or tenderness at the spot of injection, fatigue or malaise, headache, muscle pain and joint pain — and most reactions were mild or moderate.

The FDA in June authorized Novavax’s two-dose COVID-19 vaccine for adults. It authorized the updated bivalent booster vaccines from Moderna and Pfizer-BioNTech in August.

In October, the agency also authorized a booster shot of the original Novavax vaccine as an alternative to the messenger RNA vaccines.


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