CDC Study Points to Potential Benefits of Newer Flu Vaccines

CDC update

January 31, 2024 — A recent CDC study suggests that vaccination with non-egg-based flu vaccines might improve the antibody response to circulating influenza viruses over that of traditional egg-based vaccines, which are the most common flu vaccines worldwide. The study looked at people's immune response to various flu vaccines to determine which vaccines induced the best antibody response to circulating influenza viruses. The findings of this study have potential implications for flu vaccination strategy and are part of an ongoing effort to develop better flu vaccines and use existing flu vaccines to maximum effect.

For more than 70 years, most influenza (flu) vaccines have been produced by growing influenza viruses in chicken eggs. One drawback of this production method is that it often introduces changes to the viruses as they adapt to grow in eggs. These so-called "egg-adapted changes" can render the vaccine viruses significantly different from circulating "wild" influenza viruses. As a result, egg-based vaccines can prompt a person's immune system to direct antibodies at targets, or "epitopes," on the vaccine viruses that are not found on circulating viruses. This could result in reduced vaccine effectiveness (VE). Moreover, as CDC research has shown, this antibody response could be reinforced by repeated egg-based vaccination, which could contribute to further reductions in VE over time.

Now, a CDC study published in January in Nature Communications reports that multiple seasons of being vaccinated with non-egg-based flu vaccines may help refocus people's vaccine-induced immune responses to better target circulating influenza viruses. Two non-egg-based flu vaccines—the recombinant flu vaccine and the cell culture-based flu vaccine—were introduced in the United States during the 2013–14 flu season. The study, which looked at data from a randomized clinical trial conducted during the 2018–2019 and 2019–2020 influenza seasons, compared antibody responses following vaccination with recombinant, cell culture-based, or standard egg-based influenza vaccines among 1,400 people.

The results indicate that vaccination with recombinant influenza vaccine induced the most robust antibody responses against multiple vaccine viruses. They also indicate that repeated vaccination with non-egg-based flu vaccines could overcome the effect of prior repeated vaccination with egg-based vaccines. Redirecting the antibody responses away from egg-adapted epitopes resulted in higher antibody responses to cell-grown viruses that better represent circulating viruses.

The findings could inform decision-making related to optimal vaccination strategies for people in different age groups and populations.

For one, vaccination with non-egg-based flu vaccines could be especially beneficial for people who have been repeatedly vaccinated with egg-based vaccines. This could include health care personnel who have annual vaccination requirements and older adults, who tend to have been vaccinated more frequently than other groups of people. The study also adds to the evidence that when young children are first immunized against influenza (called being "primed"), they may benefit from getting a non-egg-based vaccine, as a person's first exposure to influenza virus can play a role in shaping their immune response to subsequent influenza virus infection or flu vaccinations.

Currently, recombinant and cell-based flu vaccines are the only flu vaccines made without the use of eggs that are licensed for use in the United States. The influenza viruses used in the cell-based vaccines are grown in cultured cells of mammalian origin. Recombinant flu vaccines do not require the use of a candidate vaccine virus (CVV) for production because they are created synthetically.

Some observational studies have shown greater protection against flu among people who received cell-based inactivated influenza vaccines compared with those who received standard-dose egg-based vaccines. Nevertheless, egg-based vaccines remain the most widely available flu vaccines and are an important preventive tool. The benefits of vaccination with any flu vaccine, including egg-based flu vaccine, still far outweigh the potential risks of not getting vaccinated. Currently CDC does not have a preference for the use of any one flu vaccine over another except among people 65 years and older. When available, CDC recommends people 65 years and older get a high-dose, an adjuvanted, or a recombinant flu vaccine because a review of existing studies suggested that, in this age group, these vaccines are potentially more effective than standard-dose unadjuvanted flu vaccines.

While vaccine effectiveness can vary, studies show that flu vaccination reduces the risk of flu illness by between 40% and 60% among the overall population during seasons when most circulating influenza viruses are well-matched to those used to make flu vaccines. In people who get vaccinated but still get sick, flu vaccine has been shown to reduce severity of illness, taking flu from "Wild to Mild." CDC estimates that during the 2022–2023 season, flu vaccination prevented about 6 million flu-related illnesses, 3 million medical visits, 65,000 hospitalizations, and 3,700 deaths. CDC recommends everyone 6 months and older get an annual flu vaccine.

If you have questions about which vaccine is best for you, talk to your doctor or other health care professional.