Do recombinant vaccines provide better protection against the flu than traditional vaccines?

RAIVEN: Helping determine what type of flu vaccine offers greater protection against the virus


For almost a century, vaccines that protect against the influenza virus (flu) have been manufactured from chicken eggs. However, during the past decade, several alternative influenza vaccines have been licensed by the Food and Drug Administration (FDA). These second-generation vaccines are called recombinant (new gene combination) vaccines and do not use chicken eggs in their production.

Recent evidence has shown that these recombinant vaccines may offer adults better protection against flu compared to the standard-dose egg-based flu vaccine. However, large-scale trials that evaluate laboratory-confirmed influenza outcomes are needed to confirm these preliminary findings.

The Randomized Assessment of Influenza Vaccine Efficacy Network (RAIVEN) is a joint effort between the Centers for Disease Control and Prevention (CDC), Westat, and multiple partners across the U.S. to conduct randomized trials to evaluate how well different flu vaccines protect adults against flu. One of the goals of these trials is to make them more accessible to U.S. communities, with an emphasis on including populations that have been historically underrepresented in this type of research.

During the 2022-23 influenza season, RAIVEN is conducting a randomized trial to compare the protection offered by one recombinant flu vaccine against the standard egg-based vaccine. Both vaccines are licensed for use in adults by the FDA. Participants will be randomly assigned to receive one of the study vaccines, thus reducing differences between the two groups.


Because recruiting and vaccination visits were site-based, it was critical that we identified community partners with demonstrated capabilities that aligned with the RAIVEN trial. Westat developed the partner selection criteria, including:

  • Successful experience conducting studies of a similar size and scope
  • Ability to recruit and retain participants
  • Geographic diversity and ability to recruit and enroll a population that is racially and ethnically diverse
  • Demonstrated ability to store and administer vaccines

Westat finalized our recommendations, and CDC approved our 6 research partners. These relationships with partners, some of whom have not been involved in CDC research in the past and who could reach populations historically underrepresented in vaccine trials, were major contributors to the study’s success.

During fall 2022, nearly 4,000 adults aged 18-64 years were enrolled in this trial at multiple partner sites around the country. Enrollment goals were also used to ensure racial and ethnic representation among the trial population. Enrolled participants randomly received one of the 2 trial vaccines. Both participants and study investigators were blinded to the vaccine assignments. Throughout flu season, participants were monitored for flu infection by responding to weekly text messages. When reporting that they felt ill with flu-like symptoms, participants were also asked to respond to short daily questionnaires about their illness and to send a self-collected nasal swab to the study laboratory. Nasal swabs were tested for influenza as well as COVID-19.

Westat serves as the RAIVEN coordinating center. In addition to recruiting suitable research partners, Westat worked with CDC investigators to develop the study protocol and materials. Our IT staff designed and implemented an innovative research data platform that provides electronic participant screening, consent, and enrollment. It also allows for text and email communications and surveillance. The participant dashboard component provides information on tasks that need to be completed as well as incentives earned.

Westat also vetted and established agreements with study laboratories for specimen analyses; serves as the central Institutional Review Board (IRB) for the study; and operates as the data coordinating center to collect, manage, and develop the final datasets that we will deliver to CDC.


The results of this study will provide a better understanding about whether newer vaccines provide better protection than traditional vaccines against the flu. These results could help guide national policy decisions, including preferential recommendations for particular age or risk groups, benefiting the broad U.S. adult population.


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