Abstract:
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.)