Cellular CD4 T cell responses to the diphtheria-derived carrier protein of conjugated pneumococcal vaccine and antibody response to pneumococcal vaccination in HIV-infected adults.

Background. The French National Agency for AIDS and Viral Hepatitis Research (ANRS) 114 Pneumovac trial showed that a strategy combining a 7-valent pneumococcal conjugate vaccine (PCV) prime at week 0 followed by a 23-valent pneumococcal polysaccharide vaccine (PPV) boost at week 4 enhances the frequency and magnitude of immunoglobulin (Ig) G responses against Streptococcus pneumoniae polysaccharides (SPPs) compared with PPV alone. CD4 T cell responses specific to the diphtheria-derived carrier protein CRM197 were evaluated. Methods. Lymphocyte proliferative responses (LPRs) and T(H)1 cytokine T cell responses against the diphtheria-derived carrier protein CRM197 contained in the PCV were investigated at weeks 0, 4, and 24. Results. In the prime-boost PCV and PPV group, the magnitude of LPRs to diphtheria toxoid and CRM197 increased at week 4 (P < .001) and persisted until week 24 (P = .08 and .13, respectively, compared with week 4). Interferon-gamma and interleukin-2 production to CRM197 increased significantly at week 4 (P = .02 and P < .001, respectively) and remained stable until week 24 (P = .28 and P = .08, respectively). No changes were detected in the PPV group. A strong association among the magnitude of LPRs to CRM197 at week 4, the breadth of SPP specific IgG responses at week 8 (P = .03), and sustained IgG responses at week 24 was observed. A high frequency of helper follicular CD4(+)CXCR5(+) T cells at baseline was associated with a better LPR response to CRM197. Conclusions. The PCV prime-elicited memory T cell responses were associated with better and sustained humoral SPP specific IgG responses.