High-Dose Recombinant Vaccine may Enhance Protection Against Influenza among Adults Aged 50-64

In a groundbreaking cluster-randomized observational study, Kaiser Permanente Northern California has unveiled compelling evidence supporting the superiority of a high-dose recombinant influenza vaccine over standard-dose egg-based vaccines. The study concluded that the high-dose recombinant vaccine was more protective than the standard egg-based vaccine. 

The study was conducted during the 2018–2019 and 2019–2020 influenza seasons and involved a staggering 1,630,328 vaccinees aged 18 to 64 years.

The study results were published in The New England Journal of Medicine. 

This cutting-edge research, driven by the imperative to evaluate the relative effectiveness of vaccine formulations, focused on adults aged 50 to 64 years—the primary target age group. The high-dose recombinant vaccine, known as Flublok Quadrivalent, contained an impressive three times the amount of hemagglutinin protein, a critical component for immune response, compared to conventional egg-based vaccines. Furthermore, the recombinant formulation demonstrated resilience against antigenic drift during manufacturing, a notable advantage in vaccine development. As there is uncertainty on the relative effectiveness of various vaccines, Kaiser Permanente Northern California facilities conducted a cluster-randomized observational study to evaluate the relative effectiveness of recombinant vaccines. 

The study, employing a cluster-randomized design, saw Kaiser Permanente Northern California facilities alternate weekly between the high-dose recombinant vaccine and two standard-dose influenza vaccines. The primary outcome of interest was laboratory-confirmed influenza (A or B) identified through polymerase chain reaction (PCR) testing. Secondary outcomes encompassed influenza A and B subtypes, as well as influenza-related hospitalization rates. The results, unveiled after a meticulous analysis employing Cox regression, revealed a striking disparity in vaccine effectiveness between the two formulations.

Results:

• Among participants aged 50 to 64 years, the recombinant vaccine demonstrated a 15.3% higher relative effectiveness against PCR-confirmed influenza compared to standard-dose vaccines.
• This translates to a notable reduction in influenza cases, with 559 participants per 1000 testing positive in the recombinant-vaccine group, as opposed to 925 participants per 1000 in the standard-dose group.
• Notably, the heightened protection extended to specific influenza subtypes, with the recombinant vaccine exhibiting a 15.7% higher relative effectiveness against influenza A in the same age group.
• This robust efficacy against influenza A, a strain known for its severity, underscores the potential public health impact of adopting advanced vaccine formulations.
• However, while the high-dose recombinant vaccine emerged as a standout performer in preventing PCR-confirmed influenza, it did not demonstrate a significant advantage in protecting against influenza-related hospitalization when compared to standard-dose vaccines.

In conclusion, this comprehensive study underscores the substantial benefits of the high-dose recombinant influenza vaccine for adults aged 50 to 64 years. The threefold increase in hemagglutinin protein content and resistance to antigenic drift position the recombinant formulation as a frontrunner in influenza vaccine development. As the world grapples with evolving health challenges, research of this nature paves the way for enhanced protection against seasonal influenza, offering a glimmer of hope for a healthier and more resilient future.

Further reading: Recombinant or Standard-Dose Influenza Vaccine in Adults under 65 Years of Age. N Engl J Med 2023; 389:2245-2255. DOI: 10.1056/NEJMoa2302099