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 CRM(197) were evaluated.


METHODS
Lymphocyte proliferative responses (LPRs) and T(H)1 cytokine T cell responses against the diphtheria-derived carrier protein CRM(197) 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 CRM(197) 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 CRM(197) 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 CRM(197) 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 CRM(197.)


CONCLUSIONS
The PCV prime-elicited memory T cell responses were associated with better and sustained humoral SPP specific IgG responses. ClinicalTrials.gov identifier. NCT00148824.
Rabian
Claire
C
Laboratoire d'Immunologie et d'Histocompatibilité, St. Louis Hospital, Paris, France.
Tschöpe
Inga
I
Lesprit
Philippe
P
Katlama
Christine
C
Molina
Jean-Michel
JM
Meynard
Jean-Luc
JL
Delfraissy
Jean-François
JF
Chêne
Geneviève
G
Lévy
Yves
Y
D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood*; D001426:Bacterial Proteins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D049109:Cell Proliferation; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007156:Immunologic Memory; D008297:Male; D008875:Middle Aged; D022242:Pneumococcal Vaccines / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D014611:Vaccination / Q000379:methods
C414006:23-valent pneumococcal capsular polysaccharide vaccine; D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D002352:Carrier Proteins; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D007074:Immunoglobulin G; D022242:Pneumococcal Vaccines; C028581:CRM197 (non-toxic variant of diphtheria toxin)