Evidence That Blunted CD4 T-Cell Responses Underlie Deficient Protective Antibody Responses to Influenza Vaccines in Repeatedly Vaccinated Human Subjects

Abstract Despite the benefits of yearly influenza vaccination, accumulating evidence suggests that diminished vaccine efficacy may be related to repeated vaccination. Although studied at the level of B-cell responses, CD4 T-cell responses have not yet been examined. In this study, we analyze CD4 T-cell responses to influenza vaccination in subjects who differ in their vaccine history. We find a striking disparity in their responses, with previously vaccinated subjects exhibiting significantly blunted CD4 T-cell responses and diminished antibody responses. These results suggest that limiting CD4 T-cell help mteaserrlie the diminished or altered antibody responses in repeatedly vaccinated subjects. Antibody responses to influenza vaccines are often diminished in individuals who are repeatedly vaccinated. Here, we discovered that requisite CD4 T-cell responses are similarly reduced, suggesting that early events in vaccine-induced immunity are blunted in repeatedly vaccinated subjects.