A Randomized Trial Assessing the Safety and Immunogenicity of AS01 and AS02 Adjuvanted RTS,S Malaria Vaccine Candidates in Children in Gabon

被引:65
作者
Lell, Bertrand
Agnandji, Selidji
von Glasenapp, Isabelle
Haertle, Sonja
Oyakhiromen, Sunny
Issifou, Saadou
Vekemans, Johan
Leach, Amanda
Lievens, Marc
Dubois, Marie-Claude
Demoitie, Marie-Ange
Carter, Terrell
Villafana, Tonya
Ballou, W. Ripley
Cohen, Joe
Kremsner, Peter G.
机构
[1] Medical Research Unit, Albert Schweitzer Hospital, Lambaréné
[2] GlaxoSmithKline, Biologicals, Rixensart
[3] PATH Malaria Vaccine Initiative, Bethesda, MD
[4] Bill and Melinda Gates Foundation, Seattle, WA
[5] Institute for Tropical Medicine, University of Tübingen, Tübingen
关键词
PLASMODIUM-FALCIPARUM INFECTION; PHASE 2A TRIAL; DOUBLE-BLIND; NAIVE ADULTS; RTS; S/AS02A; EFFICACY; FORMULATIONS; IMMUNIZATION; MOZAMBIQUE; PROTECTION;
D O I
10.1371/journal.pone.0007611
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: The malaria vaccine candidate antigen RTS, S includes parts of the pre-erythrocytic stage circumsporozoite protein fused to the Hepatitis B surface antigen. Two Adjuvant Systems are in development for this vaccine, an oil-in water emulsion - based formulation (AS02) and a formulation based on liposomes (AS01). Methods & Principal Findings: In this Phase II, double-blind study (NCT00307021), 180 healthy Gabonese children aged 18 months to 4 years were randomized to receive either RTS, S/AS01(E) or RTS, S/AS02(D), on a 0-1-2 month vaccination schedule. The children were followed-up daily for six days after each vaccination and monthly for 14 months. Blood samples were collected at 4 time-points. Both vaccines were well tolerated. Safety parameters were distributed similarly between the two groups. Both vaccines elicited a strong specific immune response after Doses 2 and 3 with a ratio of anti-CS GMT titers (AS02(D)/AS01(E)) of 0.88 (95% CI: 0.68-1.15) post-Dose 3. After Doses 2 and 3 of experimental vaccines, anti-CS and anti-HBs antibody GMTs were higher in children who had been previously vaccinated with at least one dose of hepatitis B vaccine compared to those not previously vaccinated. Conclusions: RTS, S/AS01(E) proved similarly as well tolerated and immunogenic as RTS, S/AS02(D), completing an essential step in the age de-escalation process within the RTS, S clinical development plan. Trial Registration: ClinicalTrials.gov.NCT00307021
引用
收藏
页数:9
相关论文
共 25 条
[1]   Duration of protection with RTS,S/AS02A malaria vaccine in prevention of Plasmodium falciparum disease in Mozambican children:: single-blind extended follow-up of a randomised controlled trial [J].
Alonso, PL ;
Sacarlal, J ;
Aponte, JJ ;
Leach, A ;
Macete, E ;
Aide, P ;
Sigauque, B ;
Milman, J ;
Mandomando, I ;
Bassat, Q ;
Guinovart, C ;
Espasa, M ;
Corachan, S ;
Lievens, M ;
Navia, MM ;
Dubois, MC ;
Menendez, C ;
Dubovsky, F ;
Cohen, J ;
Thompson, R ;
Ballou, WR .
LANCET, 2005, 366 (9502) :2012-2018
[2]   Efficacy of the RTS,S/AS02A vaccine against Plasmodium falciparum infection and disease in young African children:: randomised controlled trial [J].
Alonso, PL ;
Sacarlal, J ;
Aponte, JJ ;
Leach, A ;
Macete, E ;
Milman, J ;
Mandomando, I ;
Spiessens, B ;
Guinovart, C ;
Espasa, M ;
Bassat, Q ;
Aide, P ;
Ofori-Anyinam, O ;
Navia, MM ;
Corachan, S ;
Ceuppens, M ;
Dubois, MC ;
Demoitié, MA ;
Dubovsky, F ;
Menéndez, C ;
Tornieporth, N ;
Ballou, WR ;
Thompson, R ;
Cohen, J .
LANCET, 2004, 364 (9443) :1411-1420
[3]   Safety of the RTS,S/AS02D candidate malaria vaccine in infants living in a highly endemic area of Mozambique:: a double blind randomised controlled phase I/IIb trial [J].
Aponte, John J. ;
Aide, Pedro ;
Renom, Montse ;
Mandomando, Inacio ;
Bassat, Quique ;
Sacarlal, Jahit ;
Manaca, M. Nelia ;
Lafuente, Sarah ;
Barbosa, Arnoldo ;
Leach, Amanda ;
Lievens, Marc ;
Vekemans, Johan ;
Sigaugue, Betuel ;
Dubois, Marie-Claude ;
Demoitie, Marie-Ange ;
Sillman, Marla ;
Savarese, Barbara ;
McNeil, John G. ;
Macete, Eusebio ;
Ballou, W. Ripley ;
Cohen, Joe ;
Alonso, Pedro L. .
LANCET, 2007, 370 (9598) :1543-1551
[4]   Efficacy of RTS,S/ASO2 malaria vaccine against Plasmodium falciparum infection in semi-immune adult men in The Gambia:: a randomised trial [J].
Bojang, KA ;
Milligan, PJM ;
Pinder, M ;
Vigneron, L ;
Alloueche, A ;
Kester, KE ;
Ballou, WR ;
Conway, DJ ;
Reece, WHH ;
Gothard, P ;
Yamuah, L ;
Delchambre, M ;
Voss, G ;
Greenwood, BM ;
Hill, A ;
McAdam, KPWJ ;
Tornieporth, N ;
Cohen, JD ;
Doherty, T .
LANCET, 2001, 358 (9297) :1927-1934
[5]   Generalized convulsive seizure as an adverse event following immunization: case definition and guidelines for data collection, analysis, and presentation [J].
Bonhoeffer, J ;
Menkes, J ;
Gold, MS ;
de Souza-Brito, G ;
Fisher, MC ;
Halsey, N ;
Vermeer, P .
VACCINE, 2004, 22 (5-6) :557-562
[6]  
Breman JG, 2004, AM J TROP MED HYG, V71, P1
[7]   A phase I safety and immunogenicity trial with the candidate malaria vaccine RTS,S/SBAS2 in semi-immune adults in the Gambia [J].
Doherty, JF ;
Pinder, M ;
Tornieporth, N ;
Carton, C ;
Vigneron, L ;
Milligan, P ;
Ballou, WR ;
Holland, CA ;
Kester, KE ;
Voss, G ;
Momin, P ;
Greenwood, BM ;
McAdam, KPWJ ;
Cohen, J .
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 1999, 61 (06) :865-868
[8]   A review of human vaccine research and development: Malaria [J].
Girard, Marc P. ;
Reed, Zarifah H. ;
Friede, Martin ;
Kieny, Marie Paule .
VACCINE, 2007, 25 (09) :1567-1580
[9]   Socio-economic status is inversely related to bed net use in Gabon [J].
Goesch, Julia N. ;
Schwarz, Norbert G. ;
Decker, Marie-Luise ;
Oyakhirome, Sunny ;
Borchert, Lea B. ;
Kombila, Ulrich D. ;
Poetschke, Marc ;
Lell, Bertrand ;
Issifou, Saadou ;
Kremsner, Peter G. ;
Grobusch, Martin P. .
MALARIA JOURNAL, 2008, 7 (1)
[10]   Intermittent preventive treatment against malaria in infants in Gabon -: A randomized, double-blind, placebo-controlled trial [J].
Grobusch, Martin P. ;
Lell, Bertrand ;
Schwarz, Norbert G. ;
Gabor, Julian ;
Dornemann, Jenny ;
Poetschke, Marc ;
Oyakhirome, Sunny ;
Kiessling, Georg C. ;
Necek, Magdalena ;
Laengin, Matthias U. ;
Klouwenberg, Peter Klein ;
Kloepfer, Anna ;
Naumann, Benjamin ;
Altun, Handan ;
Agnandji, Selidji T. ;
Goesch, Julia ;
Decker, Marieluise ;
Salazar, Carmen L. Ospina ;
Supan, Christian ;
Kombila, Davy U. ;
Borchert, Lea ;
Koester, Kai B. ;
Pongratz, Peter ;
Adegnika, Akim A. ;
von Glasenapp, Isabelle ;
Issifou, Saadou ;
Kremsner, Peter G. .
JOURNAL OF INFECTIOUS DISEASES, 2007, 196 (11) :1595-1602