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.

Aging and Options to Halt Declining Immunity to Virus Infections

“…Consequently, these functional defects impair the humoral response induced by vaccination and the formation of B cell memory (347)(348)(349). It was shown that repeated vaccinations may lead to a reduced CD4 + T cell response, which correlates with a reduced antibody response (350).…”

Recombinant HA-based vaccine outperforms split and subunit vaccines in elicitation of influenza-specific CD4 T cells and CD4 T cell-dependent antibody responses in humans

“…Studies by many groups (reviewed in refs 63,64 ) have shown that individuals who were vaccinated in previous seasons have diminished HA-specific responses to influenza vaccination. We have found that the lower antibody responses in previously vaccinated subjects also exhibit diminished CD4 T-cell responses 65 . Others have shown that preexisting serum antibody levels are also associated with lower subsequent B cell and antibody responses to the influenza vaccines 66,67 .…”

Balanced Cellular and Humoral Immune Responses Targeting Multiple Antigens in Adults Receiving a Quadrivalent Inactivated Influenza Vaccine

“…Although subunit vaccines are generally considered to have limited capacity to boost cellular responses [ 23 ], recent studies have reported the induction of significant HA–specific CD4 T cell responses by Flucelvax [ 7 , 10 ]. While little is still known about the CD8 responses and their protein targets contained in this vaccine, here, we evaluated both CD4 and CD8 responses.…”

“…Current vaccines are licensed based on World Health Organization-approved centers that test the vaccine efficacy solely based on standard measures of humoral immunity. Therefore, most studies, including Flucelvax, have focused on evaluating humoral [ 9 ], as well as HA-specific CD4 dependent neutralizing antibody responses [ 10 ]. The antibody responses to any of the viral proteins other than HA are not considered or measured because their role is traditionally dismissed from an immunological and vaccine efficacy perspective.…”