Plasmodium falciparum-specific cellular immune responses after immunization with the RTS,S/AS02D candidate malaria vaccine in infants living in an area of high endemicity in Mozambique.
Results from clinical trials in areas where malaria is endemic have shown that immunization with RTS,S/AS02A malaria vaccine candidate induces partial protection in adults and children and cellular effector and memory responses in adults. For the first time in a malaria vaccine trial, we sought to assess the cell-mediated immune responses to RTS,S antigen components in infants under 1 year of age participating in a clinical phase I/IIb trial of RTS,S/AS02D in Mozambique. Circumsporozoite protein (CSP)-specific responses were detected in approximately half of RTS,S-immunized infants and included gamma interferon (IFN-gamma), interleukin-2 (IL-2), and combined IL-2/IL-4 responses. The median stimulation indices of cytokine-producing CD4(+) and CD8(+) cells were very low but significantly higher in RTS,S-immunized infants than in infants that received the comparator vaccine. Protection against subsequent malarial infection tended to be associated with a higher percentage of individuals with CSP-specific IL-2 in the supernatant (P = 0.053) and with higher CSP-specific IFN-gamma-producing CD8(+) T-cell responses (P = 0.07). These results report for the first time the detection of malaria-specific cellular immune responses after vaccination of infants less than 1 year of age and pave the way for future field studies of cellular immunity to malaria vaccine candidates.
Barbosa
Arnoldo
A
Centro de Investigação en Saúde de Manhiça, Manhiça, Mozambique.
Naniche
Denise
D
Aponte
John J
JJ
Manaca
M Nelia
MN
Mandomando
Inacio
I
Aide
Pedro
P
Sacarlal
Jahit
J
Renom
Montse
M
Lafuente
Sarah
S
Ballou
W Ripley
WR
Alonso
Pedro L
PL
D000328:Adult; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control*; D009073:Mozambique; D010919:Placebos / Q000008:administration & dosage; D010963:Plasmodium falciparum / Q000276:immunology*; D011247:Pregnancy; D015800:Protozoan Proteins / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D007376:Interleukin-2; D017780:Malaria Vaccines; D010919:Placebos; D015800:Protozoan Proteins; C533817:RTS,S-AS02D vaccine; C041595:circumsporozoite protein, Protozoan; D015847:Interleukin-4; D007371:Interferon-gamma