Experts in Industry Wrangle Over Whether Combo Vaccines Are Beneficial for Adults

WASHINGTON -- The benefits of combination vaccines may seem obvious (fewer visits, less discomfort), but their development for adults is not without challenges, pharmaceutical company experts said at the World Vaccine Congress on Wednesday.

Combination vaccines have been available for children for decades, but whether they're also needed for adults, and for which viruses, have been debated.

"I think combination vaccines have the potential for enormous public health benefit," said Kayvon Modjarrad, MD, PhD, executive director of vaccine research and development for Pfizer.

In addition to the convenience of fewer shots and fewer sore arms, combination vaccines have the potential to reduce the burden of vaccination on the overall healthcare system and improve equity, he noted.

Francesca Ceddia, MD, chief medical affairs officer for Moderna, said another perk of combined vaccines is the potential to increase coverage rates.

Despite rates of hospitalizations and deaths from COVID-19 being two to five times higher than those for influenza, people don't question flu vaccines the way they do COVID vaccines, Ceddia said, adding that she anticipates that a combination COVID/flu vaccine could help normalize COVID vaccination.

"People do not question why [they] should get diphtheria, tetanus, pertussis, etc.," she pointed out.

Ceddia also highlighted the potential to increase vaccine uptake for lesser known illnesses -- for example, by pairing vaccination for respiratory syncytial virus (RSV) with human metapneumovirus (HMPV).

The primary criteria for pairing two diseases in one vaccine is to have overlapping epidemiology and indications, the panelists said.

In the case of RSV and HMPV, both are respiratory pathogens that affect the upper and lower respiratory tracts, and both impact a similar population -- young children and older adults, Ceddia told MedPage Today in a follow-up email, adding that HMPV is "very similar" to the antigen for RSV.

The viruses also have matching seasonality and a similarly underestimated burden of disease, even more so for HMPV, she said. Moderna is working on such a vaccine and to date has completed phase I trials in pediatric populations.

Looking at less ideal combinations, duration of protection matters. It's unclear how long the current RSV vaccine will protect people, but if that duration is longer than for COVID or flu, pairing RSV with either gets increasingly more complicated. "This is what we're learning," Ceddia said, based on data that are currently being collected.

Piyali Mukherjee, MPH, vice president and head of global medical affairs, vaccines, for GSK, also noted that she sees clear benefits from combination vaccines in adults, and "with so many new technologies -- mRNA, mAbs [monoclonal antibodies] -- I'm sure this space will only grow."

Robert Walker, MD, chief medical officer for Novavax, was more skeptical.

In considering the "value proposition" of combination vaccines for adults, one should look at the injection burden and current vaccine schedule, he said. Children receive approximately 27 separate injections in their first 2 years, with as many as six in one visit.

"Clearly, there's an injection burden there, and there's a medical need," he said. "Do we have the same problem in the adult sector?"

Walker also challenged the idea that a combination flu/COVID vaccine might improve COVID vaccination uptake.

"Equally possible is that the COVID [vaccine] could be pulling the flu acceptance down," he said.

However, a 2023 meta-analysis suggested the opposite: that combining flu vaccines and COVID boosters "can be an effective strategy for increasing the uptake of the latter by populations that have shown reluctance against taking it," the authors wrote.

Ceddia is confident that the negativity and misconceptions around COVID vaccines will dissipate, she told MedPage Today, especially as awareness that vaccination prevents not only acute symptoms but also long COVID increases.

Furthermore, reducing the number of visits for vaccine administration "saves cost and time," she added. "If we assume [combination vaccines] could potentially increase compliance and adherence to vaccination, and improve coverage rates, there would be savings in terms of healthcare cost utilization."

Panelists were also asked about other specific challenges in development, including the potential for immune interference -- the belief that the immune system can become overloaded with simultaneous exposures to more than one vaccine -- and the "upper limit of toxicity" (the point at which increasing the dose of a vaccine changes the adverse event profile).

Modjarrad stressed that these are important considerations. There are already inherent complexities to developing a combination COVID/flu vaccine. For instance, there are multiple antigens present in the flu vaccine itself, which is why Pfizer is taking a "very deliberate, phased approach to this," and starting with two vaccines, not four or five, he said.

Mukherjee added that some immune interference is to be expected. That's why it's important to know what level of interference actually matters, then do studies and collect the data, she said.

As for vaccine reactogenicity, "this is where platform optimization will become very, very important," she noted. In early studies of GSK's partnership with CureVac, for example, "even at the highest dose ranges [that were tested], you do have a much lower level of reactogenicity."

Walker said that Novavax has seen interference between flu and COVID in phase II studies using recombinant protein nanoparticle platform technology, and therefore increased the amount of antigen, but the platform "can accommodate a lot of antigen."

"As we drive up antigen, our experience has been that the reactogenicity is indistinguishable from the lowest antigen dose levels," he said.

Also, as Ceddia pointed out, regulators are quick to remind companies that if a vaccine doesn't perform in the same way as the original, it's unlikely to move forward.

"It's a very complex field," she said, but knowing what has worked in the pediatric space, "there is reason to believe that it could also work in the adult space."

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