You Won't Believe How Much Better the New mRNA Flu Vaccine Is—Is Your Shot at Risk?

In a significant advancement for influenza prevention, a Phase 3 trial involving over 18,000 volunteers across three countries has demonstrated that a novel mRNA influenza vaccine developed by Pfizer outperforms traditional seasonal flu shots by an impressive 34.5%. This finding highlights the potential of mRNA technology, which gained prominence during the COVID-19 pandemic, to revolutionize influenza vaccination.

During the trial, 18,746 participants aged 18 to 64 were randomly assigned to receive either the quadrivalent modRNA influenza vaccine (modRNA) or the conventional flu shot known as Fluzone. Researchers evaluated the effectiveness of both vaccines in preventing illness, the amount of antibodies generated, and the side effects experienced by participants. Both vaccines contained two strains each of the influenza A and B viruses.

The results indicated that the relative efficacy of the modRNA vaccine compared to the control group was 34.5%, based on 57 cases in the modRNA group and 87 cases in the control group. This outcome met the study's criteria for both noninferiority and superiority. However, it's important to note that the "influenza-like illness" primarily observed in participants was largely attributed to the A/H3N2 and A/H1N1 strains, leading to inconclusive data on the mRNA vaccine’s efficacy against influenza B.

While both groups reported mostly mild or moderate side effects, the incidence was notably higher among those who received the mRNA vaccine. Local injection-site reactions occurred in 70.1% of the modRNA group compared to 43.1% in the control group. Moreover, 65.8% of the mRNA group experienced overall side effects versus 48.7% with the traditional vaccine, with fever being the most common reaction at a rate of 5.6% in the mRNA group compared to 1.7% in the control.

Professor Paul Griffin, Head of the Mater Clinical Unit at the University of Queensland School of Medicine, explained that the modRNA vaccine includes components where nucleosides are replaced by naturally occurring modified nucleosides, such as pseudouridine. This modification enhances performance and allows for faster production, offering significant advantages over traditional egg-based influenza vaccines, which can take six months or longer to prepare. This rapid production capability would enable quicker adaptation to circulating flu strains, potentially offering better protection against serious illness.

Despite the promising results, there remains skepticism surrounding mRNA technology. More than 10 years of research culminated in the rapid deployment of mRNA vaccines during the pandemic, yet concerns persist among some groups. Key advantages of mRNA technology include its ability to activate multiple arms of the immune system, including long-lived killer T cells, which can recognize various influenza strains. Dr. Emma Grant, Group Leader at the Institute for Molecular Science at La Trobe University, highlighted that this study indicated increased cellular responses compared to traditional vaccines, moving closer to the long-sought goal of a "universal" influenza vaccine.

However, the study has limitations. It was funded by Pfizer and conducted with independent researchers in the U.S., South Africa, and the Philippines. Critics have pointed out the absence of older populations in the trial, a demographic particularly vulnerable to complications from influenza. Sanjaya Senanayake, an infectious diseases specialist and Associate Professor of Medicine at The Australian National University, expressed concern over this omission and the higher incidence of side effects from the mRNA vaccine, which could hinder public acceptance at a time when vaccine skepticism is already pronounced.

Vinod Balasubramaniam, a molecular virologist and Associate Professor at Monash University Malaysia, noted that while the side effects were predominantly mild to moderate and short-lived, their frequency could discourage uptake among potential recipients. Despite these challenges, it is crucial to weigh the cost-effectiveness of the mRNA vaccine against traditional flu vaccines, as governmental funding will be necessary for widespread implementation.

Importantly, the trial did not report any incidences of myocarditis or pericarditis among participants, conditions that had raised concerns with earlier mRNA vaccines. Dr. Rodney Pearce AM, Chair of the Immunization Coalition, stated that the absence of such incidents may suggest that these effects are more closely associated with COVID vaccines rather than inherent to mRNA technology itself.

While competitors like Moderna are also pursuing mRNA flu vaccines, they recently faced setbacks with disappointing early trial results. As the field progresses, the implications of Pfizer’s findings could spur further research and development in mRNA technology for vaccines against a range of viral illnesses, potentially improving public health outcomes.

The findings from this study were published in the New England Journal of Medicine, signaling a noteworthy step forward in the quest for more effective influenza vaccines. As research continues, the hope remains that mRNA technology can provide broader and longer-lasting protection against influenza variants, ushering in a new era of vaccination.