Can I Boost With Novavax?

 While the recently FDA-authorized Novavax vaccine (NVX-CoV2373) was originally seen as a way to convince the unvaccinated to get their COVID shot, some researchers say its main role now likely will be as a booster.

The protein subunit vaccine -- a more traditional vaccination technology -- may be particularly appealing to those who were sidelined by side effects from mRNA vaccines, who may be hopeful for an easier booster experience; though whether it will produce fewer side effects in this setting remains to be seen.

Researchers have also raised earlier questions about whether mixing and matching boosters can lead to better immunity, especially as new variants evolve.

While the Novavax shot is not yet authorized by the FDA as a booster, several experts told MedPage Today it could be headed that way.

"Probably the best niche now for Novavax's purified protein vaccine is as a booster strategy for mRNA vaccines," Paul Offit, MD, of Children's Hospital of Philadelphia, who served on the FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC) on Novavax, told MedPage Today.

Robert "Chip" Schooley, MD, an infectious disease expert at the University of California San Diego who has served on VRBPAC in the past, said since there "aren't many people left who have been neither vaccinated nor infected ... it will likely be mainly used as a booster."

Schooley noted that there are no data yet as to whether Novavax-as-a-booster can provide as much protection as mRNA boosters, or if it can provide substantial protection against recent Omicron variants.

"We'll not see efficacy (infection prevention) data any time soon, but one would guess that this vaccine would provide enough stimulation in a booster format to benefit the host," Schooley said.

During the VRBPAC hearing on Novavax in June, Offit said the company confirmed it was studying its vaccine as a booster in various scenarios including on top of mRNA vaccines. Indeed, on May 31, the company announced that it had initiated a phase III trial of its vaccine as a booster in people who previously got mRNA vaccines.

According to ClinicalTrials.gov, the study will evaluate booster doses of monovalent or bivalent versions of its vaccine, on top of at least two doses of either the Moderna or Pfizer vaccine.

However, that study lists an expected completion date of July 2023 and is listed as "active, not recruiting."

The company is also participating in an ongoing NIH phase I/II "mix and match" trial evaluating fully vaccinated adults getting booster doses of different COVID vaccines.

Novavax told MedPage Today in an email that it presented preclinical trial data to VRBPAC showing that homologous boosting with the initial vaccine, an Omicron BA.1-specific vaccine, or a bivalent vaccine, "generated antibody levels that were consistent with dosing regimens in the phase III clinical trial."

Fewer Side Effects, Broader Immunity?

Questions remain about some of the key reasons people would want to boost with Novavax -- notably, for potentially fewer side effects, or for potentially broader immunity.

Katelyn Jetelina, PhD, MPH, an epidemiologist at UTHealth in Dallas, noted in an earlier Substack post that based on existing data, a Novavax boost may not be as powerful as she would have hoped.

A study in The Lancet showed that a single dose of an mRNA vaccine plus a single dose of Novavax didn't produce as robust an antibody response as two doses of mRNA, she said. A paper in Science found comparable antibody responses between three doses of mRNA vaccines versus two doses of Novavax plus one dose of mRNA. Finally, another study in The Lancet showed two doses of mRNA plus a Novavax booster didn't provide an advantage in antibody response over other vaccine and booster combinations, Jetelina said.

"This study shows that combining can be advantageous for certain vaccines, but that doesn't seem to be the case for mRNA and Novavax," she wrote.

She did note that effects on durability remain to be seen. It could be that a Novavax booster on top of mRNA vaccines slows the rapid waning in protection against infection of these vaccines, but this is an open question.

For those who are hopeful about diminished side effects, there's even less evidence to go on, said Alex Sette, DrBiolSci, of La Jolla Institute for Immunology in California.

"Certainly it would be an interesting possibility, as it would be expected that the mechanisms that cause reactions may be different," he told MedPage Today in an email.

That said, he warned, he hasn't seen any data on side effects comparing these booster strategies. "I am not sure one can say that side effects are less," he said. "Some of the mRNA side effects are very rare and Novavax has been in relatively fewer people thus far, so a balanced comparison is currently difficult."

"It should be noted that the Pfizer and Moderna mRNA vaccines seem to have different reaction patterns, so in that respect a mix-match approach could also be considered," he added.

Offit agreed that the side effect profile of boosting with Novavax is unknown: "Fever, headache, pain might not be better," he said. "We'll have to see."

Jetelina warned against any delays in getting a booster for authorized groups as the latest Omicron variant surge continues: "For now, I don't recommend using Novavax off-label as a booster, or worse, waiting for a booster because Novavax is coming."

https://www.medpagetoday.com/special-reports/exclusives/99932