Evaluation of the safety and immunogenicity of the RTS,S/AS01E malaria candidate vaccine when integrated in the expanded program of immunization.
BACKGROUND
The RTS,S/AS01(E) malaria candidate vaccine is being developed for immunization of African infants through the Expanded Program of Immunization (EPI).


METHODS
This phase 2, randomized, open, controlled trial conducted in Ghana, Tanzania, and Gabon evaluated the safety and immunogenicity of RTS,S/AS01(E) when coadministered with EPI vaccines. Five hundred eleven infants were randomized to receive RTS,S/AS01(E) at 0, 1, and 2 months (in 3 doses with diphtheria, tetanus, and whole-cell pertussis conjugate [DTPw]; hepatitis B [HepB]; Haemophilus influenzae type b [Hib]; and oral polio vaccine [OPV]), RTS,S/AS01(E) at 0, 1, and 7 months (2 doses with DTPwHepB/Hib+OPV and 1 dose with measles and yellow fever), or EPI vaccines only.


RESULTS
The occurrences of serious adverse events were balanced across groups; none were vaccine-related. One child from the control group died. Mild to moderate fever and diaper dermatitis occurred more frequently in the RTS,S/AS01(E) coadministration groups. RTS,S/AS01(E) generated high anti-circumsporozoite protein and anti-hepatitis B surface antigen antibody levels. Regarding EPI vaccine responses upon coadministration when considering both immunization schedules, despite a tendency toward lower geometric mean titers to some EPI antigens, predefined noninferiority criteria were met for all EPI antigens except for polio 3 when EPI vaccines were given with RTS,S/AS01(E) at 0, 1, and 2 months. However, when antibody levels at screening were taken into account, the rates of response to polio 3 antigens were comparable between groups.


CONCLUSIONS
RTS,S/AS01(E) integrated in the EPI showed a favorable safety and immunogenicity evaluation. Trial registration. ClinicalTrials.gov identifier: NCT00436007 . GlaxoSmithKline study ID number: 106369 (Malaria-050).
Agnandji
Selidji T
ST
Albert Schweitzer Hospital, Medical Research Unit Lambaréné, Lambaréné, Gabon. agnandjis@yahoo.fr
Asante
Kwaku Poku
KP
Lyimo
John
J
Vekemans
Johan
J
Soulanoudjingar
Solange S
SS
Owusu
Ruth
R
Shomari
Mwanajaa
M
Leach
Amanda
A
Fernandes
Jose
J
Dosoo
David
D
Chikawe
Maria
M
Issifou
Saadou
S
Osei-Kwakye
Kingsley
K
Lievens
Marc
M
Paricek
Maria
M
Apanga
Stephen
S
Mwangoka
Grace
G
Okissi
Blaise
B
Kwara
Evans
E
Minja
Rose
R
Lange
Jorn
J
Boahen
Owusu
O
Kayan
Kingsley
K
Adjei
George
G
Chandramohan
Daniel
D
Jongert
Erik
E
Demoitié
Marie-Ange
MA
Dubois
Marie-Claude
MC
Carter
Terrel
T
Vansadia
Preeti
P
Villafana
Tonya
T
Sillman
Marla
M
Savarese
Barbara
B
Lapierre
Didier
D
Ballou
William Ripley
WR
Greenwood
Brian
B
Tanner
Marcel
M
Cohen
Joe
J
Kremsner
Peter G
PG
Lell
Bertrand
B
Owusu-Agyei
Seth
S
Abdulla
Salim
S
D016667:Bacterial Capsules / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D005260:Female; D005681:Gabon; D005869:Ghana; D018073:Haemophilus Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D006801:Humans; D007114:Immunization / Q000379:methods*; D007117:Immunization, Secondary / Q000379:methods; D007223:Infant; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D008297:Male; D011055:Poliovirus Vaccine, Oral / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D013636:Tanzania
D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; C044237:Haemophilus influenzae type b polysaccharide vaccine; D017325:Hepatitis B Vaccines; D017780:Malaria Vaccines; D011055:Poliovirus Vaccine, Oral; C533816:RTS,S-AS01E vaccine