Blunted Vaccine-Induced Immunity in Repeatedly Vaccinated People

influenza virus., antibodies
influenza virus., antibodies
Early events in vaccine-induced immunity may be blunted in repeatedly vaccinated individuals.

Early events in vaccine-induced immunity may be blunted in repeatedly vaccinated individuals, according to a study published in the Journal of Infectious Diseases.

Many countries recommend annual influenza vaccination; however, the protection these vaccines provide varies among individuals and depends in part on the match with the strains that ultimately emerge in the subsequent influenza season. Despite benefits of getting vaccinated for influenza annually, increasing evidence suggests that repeated vaccination may lead to diminished vaccine efficacy. Although the role of CD4 T cells in facilitating the antibody responses to influenza vaccination have been well documented, CD4 T-cell responses to influenza vaccination in individuals who have been previously vaccinated has not been compared with those without vaccination history. Therefore, this study analyzed CD4 T-cell responses to influenza vaccination in individuals with different vaccine histories.

In total, 78 healthy adults were included and evaluated over the course of 2 successive seasons. Participants provided blood samples on day 0 and on days 7, 14, and 28 after vaccination with licensed influenza vaccines, which included Fluzone, Flucelvax, and Flublok. Both CD4 T-cell and B-cell responses to influenza vaccination were evaluated. At the time of enrollment, participants self-reported their previous year’s influenza vaccine history. On the basis of participants’ responses on whether or not they had received an influenza vaccine in the previous season, results were comparatively analyzed. CD4 T-cell responses to vaccination were assessed by the presence of circulating CD4 T cells that express markers associated with the follicular helper cell response. In the vaccinated group, the mean age was 29 years. In the nonvaccinated group, the mean age was 27 years.

Results showed that people who had been previous vaccinated exhibit significantly blunted CD4 T-cell responses and diminished antibody responses. By day 14 postvaccination in participants who were not previously vaccinated, CD4 T cells reactive with each of the HA-derived epitopes (H1, H3, and HA-B) were significantly amplified by 2- to 3-fold (H1, P =.0054; H3, P =.004; HA-B, P <.0001). On day 7 postvaccination, CD4 T cells expressing CXCR5, PD1, and ICOS (markers used to identify follicular helper cells) were quantified.

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Unvaccinated participants had a more robust CD4 T helper cell responses to vaccination, with 3-fold greater follicular helper cells in the blood compared with individuals who were previously vaccinated (P <.0001). This suggests participants who were previously vaccinated mounted a significantly less robust hemagglutinin-specific CD4 T-cell response when compared with those who were unvaccinated. Further, a similar pattern in hemagglutinin-specific responses was observed when HAI titers, reflecting antibodies that detect the specific regions on the head hemagglutinin protein associated with binding to red blood cells, the most commonly used correlate of protection, were measured. In participants that were previously vaccinated, HAI titers were significantly less robust after vaccination (H1N1, P =.034; H3N2, P =.0009; B-Phuket, P <.0001; B-Brisbane, P =.0006), which indicated that an influenza vaccination in the previous season diminished the vaccine-induced antibody response in the following year, and data support that these elicited antibody responses are statistically and positively correlated with the elicited CD4 T-cell response to each of the hemagglutinin proteins.

Overall, the study authors concluded that, “These results suggest that limited CD4 T cell help may underlie the diminished or altered antibody responses in repeatedly vaccinated [people].”


Richards KA, Shannon I, Treanor JJ, Yang H, Nayak JL, Sant AJ. Evidence that blunted CD4 T cells responses underlie deficient protective antibody responses to influenza vaccines in repeatedly vaccinated human subjects [published online August 26, 2019]. J Infect Dis. doi:10.1093/infdis/jiz433/5554480