FDA Committee Recommends Development of Monovalent, XBB-Containing Vaccines

The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) has unanimously recommended that COVID-19 vaccines being developed for deployment this Fall should only include protection against the now-dominant XBB variant SARS-CoV-2 virus.¹

Although rates of infection have slowed, “We’re concerned that we may have another wave of COVID-19 during a time when the virus has further evolved, immunity of the population has waned further, and we move indoors for wintertime,” said Peter Marks, MD, PhD, director of the Center for Biologics Evaluation and Research.²

Omicron subvariants XBB.1.5, XBB.1.16, and XBB.2.3 are responsible for most of the current COVID-19 infections in the United States, with 39.9% of cases due to XBB.1.5³—making it the preferred target for updated vaccines. VRBPAC panel members also recommended that manufacturers more away from the previous bivalent vaccine design into a monovalent vaccine targeting XBB subvariants, which “elicits stronger neutralizing antibody responses” compared with current bivalent vaccines.

Although committee members agreed around the shift from bivalent to monovalent immunization, there was “considerable debate,” according to an NPR report,⁴ over whether COVID-19 vaccines should be handled in the same way as influenza vaccines: reformulated each year based on circulating strains.

Marks pointed out that people “understand a yearly influenza vaccine. At this point it may not be yearly, but, for all intents and purposes, it looks like by next fall there will be further drift from this [strain] and we may have to come back here.” However, Paul A. Offit, MD, professor of pediatrics at the Children’s Hospital of Philadelphia, pointed out that COVID-19 “is not the flu,” adding that there remains a need to define “who really benefits from booster dosing…Because it’s not everybody.”⁴

Manufacturer Updates

Vaccine manufacturers Pfizer, Moderna, and Novavax each presented preclinical data from research around updated versions of their COVID-19 vaccines targeting the XBB.1.5 variant. Representatives from Pfizer said that the company would be able to distribute reformulated vaccine doses as early as the end of July, depending on which vaccine strain was selected, while Moderna representatives expect to begin delivering updated vaccine doses by the end of the summer. In a press release distributed after the meeting, Novavax indicated that the company would be able to begin delivering their updated vaccine this fall.

“The fact that most of the manufacturers are ready to work on XBB.1.5 is an added reason to select this strain or this variant, given the immunologic data, said Arnold Monto, MD, VRBPAC meeting chair.⁵

“Now that we are nearing harmonization on guidance from the FDA, the World Health Organization, and [the] European Medicines Agency, we believe we are in a better position to offer an alternative vaccine choice for individuals worldwide,” said John C. Jacobs, Novavax president and CEO.⁶ Data presented by the company at the VRBPAC meeting demonstrated that the company’s XBB.1.5 vaccine “included functional immune responses for XBB.1.5, XBB.1.16, and XBB.2.3 variants, indicating a broad response that could potentially be applicable for forward-drift variants.”

The Novavax COVID-19 vaccine, adjuvanted, has not yet been approved or licensed by the FDA. However, the vaccine—a protein-based vaccine using the company’s novel Matrix-M adjuvant—has been authorized under an Emergency Use Authorization as a primary series vaccine for individuals aged 12 years and older. It is also authorized for use as a first booster dose at least 6 months after completion of a primary vaccination series in adults aged 18 years or older.

Darin Edwards, PhD, executive director and COVID-19 Program Lead at Moderna, presented the company’s preclinical data, which demonstrated that XBB-containing vaccines are “more immunogenic against currently circulating XBB variants.”⁷ Edwards was followed by Rituparna Das, MD, PhD, vice president of COVID vaccines at Moderna, who discussed data from a clinical trial of investigational XBB.1.5 variant-containing vaccines.

Results of that trial (NCT04927065) showed that among 101 participants who had previously received 4 doses of a COVID-19 vaccine, an XBB-containing vaccine was more immunogenic against the currently circulating XBB variants, compared with the currently authorized BA.4/5 vaccines. These vaccines also elicit robust neutralizing antibodies against these variants, with a consistent safety profile to previously authorized vaccines.

Kena A. Swanson, PhD, vice president of viral vaccine research and development at Pfizer, also shared results of preclinical vaccine research around XBB-containing vaccine candidates as both a primary series and booster dose.⁷ Compared with the current BA.4/5 vaccines, XBB.1.5-containing booster doses showed that a monovalent XBB.1.5 booster elicited the highest neutralizing titers against each evaluated XBB sublineage, including XBB.1.16 and XBB.2.3. As a 2-dose primary series, a monovalent XBB.1.5 vaccine generated the highest neutralizing titers against the same XBB strains.

An official decision from the FDA around the vaccine formulation is anticipated in the coming days.

References

1. Cosdon N. COVID-19 vaccines should be monovalent and contain XBB strain, FDA committee recommends. Contagion. June 15, 2023. Accessed June 16, 2023. https://www.contagionlive.com/view/covid-19-vaccines-should-be-monovalent-and-contain-the-xbb-strain-fda-committee-recommends

2. Neergaard L, Stobbe M. FDA advisers endorse updating COVID vaccines to target latest omicron strain. Associated Press. June 15, 2023. Accessed June 16, 2023. https://apnews.com/article/covid19-vaccine-booster-shot-coronavirus-fall-72c0436ac9211f1a893fe8056106909d

3. What COVID-19 variants are going around in June 2023? Nebraska Medicine. June 15, 2023. Accessed June 16, 2023. https://www.nebraskamed.com/COVID/what-covid-19-variants-are-going-around

4. Huang P, Stone W. FDA advisers back updated COVID shots for fall vaccinations. NPR. June 15, 2023. Accessed June 16, 2023. https://www.npr.org/sections/health-shots/2023/06/15/1182503195/fda-advisers-back-updated-covid-shots-for-fall-vaccinations

5. Satija B, Roy S. FDA advisers back updated COVID vaccine targeting dominant variant. Reuters. June 15, 2023. Accessed June 16, 2023. https://www.reuters.com/business/healthcare-pharmaceuticals/us-fda-panel-weigh-makeup-next-covid-vaccine-2023-06-15

6. Novavax prepared to deliver protein-based monovalent XBB COVID vaccine consistent with FDA VRBPAC recommendation for the fall. News release. Novavax. June 15, 2023. Accessed June 16, 2023. https://www.prnewswire.com/news-releases/novavax-prepared-to-deliver-protein-based-monovalent-xbb-covid-vaccine-consistent-with-fda-vrbpac-recommendation-for-the-fall-301852622.html

7. Vaccines and Related Biological Products Advisory Committee June 15, 2023 meeting announcement. FDA. June 15, 2023. Accesed June 16, 2023. https://www.fda.gov/advisory-committees/advisory-committee-calendar/vaccines-and-related-biological-products-advisory-committee-june-15-2023-meeting-announcement