Safety and immunogenicity of RTS,S/AS02D malaria vaccine in infants.
BACKGROUND
The RTS,S/AS malaria vaccine is being developed for delivery through the World Health Organization's Expanded Program on Immunization (EPI). We assessed the feasibility of integrating RTS,S/AS02D into a standard EPI schedule for infants.


METHODS
In this phase 2B, single-center, double-blind, controlled trial involving 340 infants in Bagamoyo, Tanzania, we randomly assigned 340 infants to receive three doses of either the RTS,S/AS02D vaccine or the hepatitis B vaccine at 8, 12, and 16 weeks of age. All infants also received a vaccine containing diphtheria and tetanus toxoids, whole-cell pertussis vaccine, and conjugated Haemophilus influenzae type b vaccine (DTPw/Hib). The primary objectives were the occurrence of serious adverse events during a 9-month surveillance period and a demonstration of noninferiority of the responses to the EPI vaccines (DTPw/Hib and hepatitis B surface antigen) with coadministration of the RTS,S/AS02D vaccine, as compared with the hepatitis B vaccine. The detection of antibodies against Plasmodium falciparum circumsporozoite and efficacy against malaria infection were secondary objectives.


RESULTS
At least one serious adverse event was reported in 31 of 170 infants who received the RTS,S/AS02D vaccine (18.2%; 95% confidence interval [CI], 12.7 to 24.9) and in 42 of 170 infants who received the hepatitis B vaccine (24.7%; 95% CI, 18.4 to 31.9). The results showed the noninferiority of the RTS,S/AS02D vaccine in terms of antibody responses to EPI antigens. One month after vaccination, 98.6% of infants receiving the RTS,S/AS02D vaccine had seropositive titers for anticircumsporozoite antibodies on enzyme-linked immunosorbent assay (ELISA). During the 6-month period after the third dose of vaccine, the efficacy of the RTS,S/AS02D vaccine against first infection with P. falciparum malaria was 65.2% (95% CI, 20.7 to 84.7; P=0.01).


CONCLUSIONS
The use of the RTS,S/AS02D vaccine in infants had a promising safety profile, did not interfere with the immunologic responses to coadministered EPI antigens, and reduced the incidence of malaria infection. (ClinicalTrials.gov number, NCT00289185.)
Abdulla
Salim
S
Bagamoyo Research and Training Centre of Ifakara Health Institute, Bagamoyo, Tanzania. sabdulla@ihi.or.tz
Oberholzer
Rolf
R
Juma
Omar
O
Kubhoja
Sulende
S
Machera
Francisca
F
Membi
Christopher
C
Omari
Said
S
Urassa
Alwisa
A
Mshinda
Hassan
H
Jumanne
Ajuza
A
Salim
Nahya
N
Shomari
Mwanjaa
M
Aebi
Thomas
T
Schellenberg
David M
DM
Carter
Terrell
T
Villafana
Tonya
T
Demoitié
Marie-Ange
MA
Dubois
Marie-Claude
MC
Leach
Amanda
A
Lievens
Marc
M
Vekemans
Johan
J
Cohen
Joe
J
Ballou
W Ripley
WR
Tanner
Marcel
M
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D001428:Bacterial Vaccines; D004311:Double-Blind Method; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D010963:Plasmodium falciparum / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology
D000913:Antibodies, Protozoan; D001428:Bacterial Vaccines; D006514:Hepatitis B Surface Antigens; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C533817:RTS,S-AS02D vaccine; C041595:circumsporozoite protein, Protozoan