CDC Study Finds Potential Enhanced Benefit of Recombinant Flu Vaccines

August 16, 2021—A new CDC study showed that flu shots made using recombinant technology produced a better antibody response among health care personnel compared with both cell-based and traditional flu shots. The study, conducted during the 2018-2019 flu season, compared antibody responses among health care personal one month and six-months post-vaccination between recombinant (RIV), cell-based (ccIV), and traditional egg-based flu shots (IIV). The immune responses generated by recombinant vaccine outperformed those of both the cell-based and the standard dose flu vaccines made using traditional egg-based technology. While not definitive, this suggests that vaccine effectiveness may be higher for recombinant flu vaccines.

For decades flu vaccines have been produced by growing flu viruses in eggs, which is required for egg-based vaccine production. This production technology has some drawbacks including the fact that growth in eggs can cause mutations in the vaccine viruses that can impact how well the vaccines work. Recombinant and cell-based vaccines are produced using a different production process that does not require growth in eggs.

To compare the immune responses produced by RIV and ccIIV, researchers conducted a randomized, open-label trial among health care personnel. Participants were randomized to receive either ccIIV, RIV, or IIV. Serum specimens were collected pre-vaccination, one month post-vaccination, and six-months post-vaccination, so that researchers could compare whether antibody responses against the vaccine viruses were present among recipients of the different vaccines.

Researchers found no consistent differences in antibody responses between participants that received ccIIV and those who received the egg-based IIV. However, all three vaccine types: egg-based IIV, ccIIV, and RIV still elicited immune responses against the flu virus strains these vaccines were designed to protect against.

This study is subject to several limitations. Researchers were unable to look at the role of prior vaccination on immune responses because most participants had received annual flu vaccines during all five seasons before this study. Also, the study sample may have been subject to selection bias if health care personnel who agreed to participate were more accepting of flu vaccines, and therefore, were more likely to get vaccinated.

This trial focused on antibody-mediated immunity against hemagglutinin (a protein on the surface of influenza viruses) and may not directly translate to differences in protection against flu viruses. Previous trials have demonstrated that recombinant flu vaccines provide better protection than egg-based inactivated influenza vaccines in adults 50 years and older; however, large-scale efficacy trials are needed to understand whether RIV or ccIV provide more robust protection against flu in younger adults.

These findings support a possible additional benefit from flu vaccination with recombinant flu vaccines. Additional studies are needed to assess whether these findings remain consistent over multiple seasons, with different vaccine virus compositions, and across other markers of immune response. Such studies will also need to assess vaccine benefits against laboratory-confirmed outcomes to minimize bias and ensure accuracy of the findings.

This study is available for viewing on Clinical Infectious Diseases online.