A Phase 3 Trial of RTS,S/AS01 Malaria Vaccine in African Infants

被引：547

作者：

Mian-McCarthy, Sara ^{[19
]}

Agnandji, Selidji Todagbe ^{[1
,2
]}

Lell, Bertrand ^{[1
,2
]}

Fernandes, Jose Francisco ^{[1
,2
]}

Abossolo, Beatrice Peggy ^{[1
,2
]}

Methogo, Barbara Gaelle Nfono Ondo ^{[1
,2
]}

Kabwende, Anita Lumeka ^{[1
,2
]}

Adegnika, Ayola Akim ^{[1
,2
]}

Mordmueller, Benjamin ^{[1
,2
]}

Issifou, Saadou ^{[1
,2
]}

Kremsner, Peter Gottfried ^{[1
,2
]}

Sacarlal, Jahit ^{[3
,4
]}

Aide, Pedro ^{[3
,4
]}

Lanaspa, Miguel ^{[3
,4
]}

Aponte, John J. ^{[3
,4
]}

Machevo, Sonia ^{[3
,4
]}

Acacio, Sozinho ^{[3
,4
]}

Bulo, Helder ^{[3
,4
]}

Sigauque, Betuel ^{[3
,4
]}

Macete, Eusebio ^{[3
,4
]}

Alonso, Pedro ^{[3
,4
]}

Abdulla, Salim ^{[5
,6
]}

Salim, Nahya ^{[5
,6
]}

Minja, Rose ^{[5
,6
]}

Mpina, Maxmillian ^{[5
,6
]}

Ahmed, Saumu ^{[5
,6
]}

Ali, Ali Mohammed ^{[5
,6
]}

Mtoro, Ali Takadir ^{[5
,6
]}

Hamad, Ali Said ^{[5
,6
]}

Mutani, Paul ^{[5
,6
]}

Tanner, Marcel ^{[5
,6
]}

Tinto, Halidou ^{[7
,8
]}

D'Alessandro, Umberto ^{[7
,8
]}

Sorgho, Hermann ^{[7
,8
]}

Valea, Innocent ^{[7
,8
]}

Bihoun, Biebo ^{[7
,8
]}

Guiraud, Issa ^{[7
,8
]}

Kabore, Berenger ^{[7
,8
]}

Sombie, Olivier ^{[7
,8
]}

Guiguemde, Robert Tinga ^{[7
,8
]}

Ouedraogo, Jean Bosco ^{[7
,8
]}

Hamel, Mary J. ^{[9
]}

Kariuki, Simon ^{[9
]}

Oneko, Martina ^{[9
]}

Odero, Chris ^{[9
]}

Otieno, Kephas ^{[9
]}

Awino, Norbert ^{[9
]}

McMorrow, Meredith ^{[9
]}

Muturi-Kioi, Vincent ^{[9
]}

Laserson, Kayla F. ^{[9
]}

机构：

[1] Albert Schweitzer Hosp, Lambarene, Gabon

[2] Univ Tubingen, Inst Trop Med, Tubingen, Germany

[3] Ctr Invest Saude Manhica, Manhica, Mozambique

[4] Univ Barcelona, Barcelona Ctr Int Hlth Res CRESIB, Hosp Clin, Barcelona, Spain

[5] Ifakara Hlth Inst, Bagamoyo, Tanzania

[6] Swiss Trop & Publ Hlth Inst, Basel, Switzerland

[7] Inst Rech Sci Sante, Nanoro, Burkina Faso

[8] Inst Trop Med, B-2000 Antwerp, Belgium

[9] KEMRI CDC Res & Publ Hlth Collaborat, Kisumu, Kenya

[10] KEMRI Walter Reed Project, Kombewa, Kenya

[11] KEMRI Wellcome Trust Res Program, Kilifi, Kenya

[12] Kintampo Hlth Res Ctr, Kintampo, Ghana

[13] London Sch Hyg & Trop Med, London, England

[14] Natl Inst Med Res, Korogwe, Tanzania

[15] Univ Copenhagen, Copenhagen, Denmark

[16] Sch Med Sci, Kumasi, Ghana

[17] Univ N Carolina Project, Lilongwe, Malawi

[18] GlaxoSmithKline Vaccines, Wavre, Belgium

[19] PATH Malaria Vaccine Initiat, Commun & Advocacy Unit, Washington, DC 20001 USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2012年 / 367卷 / 24期

关键词：

III MULTICENTER TRIAL; CANDIDATE VACCINE; CASE-DEFINITION; FALCIPARUM-MALARIA; DATA-COLLECTION; DOUBLE-BLIND; SAFETY; IMMUNOGENICITY; EFFICACY; IMMUNIZATION;

D O I：

10.1056/NEJMoa1208394

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND The candidate malaria vaccine RTS,S/AS01 reduced episodes of both clinical and severe malaria in children 5 to 17 months of age by approximately 50% in an ongoing phase 3 trial. We studied infants 6 to 12 weeks of age recruited for the same trial. METHODS We administered RTS,S/AS01 or a comparator vaccine to 6537 infants who were 6 to 12 weeks of age at the time of the first vaccination in conjunction with Expanded Program on Immunization (EPI) vaccines in a three-dose monthly schedule. Vaccine efficacy against the first or only episode of clinical malaria during the 12 months after vaccination, a coprimary end point, was analyzed with the use of Cox regression. Vaccine efficacy against all malaria episodes, vaccine efficacy against severe malaria, safety, and immunogenicity were also assessed. RESULTS The incidence of the first or only episode of clinical malaria in the intention-to-treat population during the 14 months after the first dose of vaccine was 0.31 per person-year in the RTS,S/AS01 group and 0.40 per person-year in the control group, for a vaccine efficacy of 30.1% (95% confidence interval [ CI], 23.6 to 36.1). Vaccine efficacy in the per-protocol population was 31.3% (97.5% CI, 23.6 to 38.3). Vaccine efficacy against severe malaria was 26.0% (95% CI, -7.4 to 48.6) in the intention-to-treat population and 36.6% (95% CI, 4.6 to 57.7) in the per-protocol population. Serious adverse events occurred with a similar frequency in the two study groups. One month after administration of the third dose of RTS,S/AS01, 99.7% of children were positive for anti-circumsporozoite antibodies, with a geometric mean titer of 209 EU per milliliter (95% CI, 197 to 222). CONCLUSIONS The RTS,S/AS01 vaccine coadministered with EPI vaccines provided modest protection against both clinical and severe malaria in young infants. (Funded by GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov number, NCT00866619.)

引用

页码：2284 / 2295

页数：12

共 33 条

[1] Safety and Immunogenicity of RTS,S/AS02D Malaria Vaccine in Infants [J].

Abdulla, Salim ;

Oberholzer, Rolf ;

Juma, Omar ;

Kubhoja, Sulende ;

Machera, Francisca ;

Membi, Christopher ;

Omari, Said ;

Urassa, Alwisa ;

Mshinda, Hassan ;

Jumanne, Ajuza ;

Salim, Nahya ;

Shomari, Mwanjaa ;

Aebi, Thomas ;

Schellenberg, David M. ;

Carter, Terrell ;

Villafana, Tonya ;

Demoitie, Marie-Ange ;

Dubois, Marie-Claude ;

Leach, Amanda ;

Lievens, Marc ;

Vekemans, Johan ;

Cohen, Joe ;

Ballou, W. Ripley ;

Tanner, Marcel .

NEW ENGLAND JOURNAL OF MEDICINE, 2008, 359 (24) :2533-2544

[2] Evaluation of the Safety and Immunogenicity of the RTS,S/AS01E Malaria Candidate Vaccine when Integrated in the Expanded Program of Immunization (vol 202, pg 1076, 2010) [J].

Agnandji, Selidji .

JOURNAL OF INFECTIOUS DISEASES, 2011, 203 (09) :1344-1344

[3] Evaluation of the Safety and Immunogenicity of the RTS,S/AS01E Malaria Candidate Vaccine When Integrated in the Expanded Program of Immunization [J].

Agnandji, Selidji T. ;

Asante, Kwaku Poku ;

Lyimo, John ;

Vekemans, Johan ;

Soulanoudjingar, Solange S. ;

Owusu, Ruth ;

Shomari, Mwanajaa ;

Leach, Amanda ;

Fernandes, Jose ;

Dosoo, David ;

Chikawe, Maria ;

Issifou, Saadou ;

Osei-Kwakye, Kingsley ;

Lievens, Marc ;

Paricek, Maria ;

Apanga, Stephen ;

Mwangoka, Grace ;

Okissi, Blaise ;

Kwara, Evans ;

Minja, Rose ;

Lange, Jorn ;

Boahen, Owusu ;

Kayan, Kingsley ;

Adjei, George ;

Chandramohan, Daniel ;

Jongert, Erik ;

Demoitie, Marie-Ange ;

Dubois, Marie-Claude ;

Carter, Terrel ;

Vansadia, Preeti ;

Villafana, Tonya ;

Sillman, Marla ;

Savarese, Barbara ;

Lapierre, Didier ;

Ballou, William Ripley ;

Greenwood, Brian ;

Tanner, Marcel ;

Cohen, Joe ;

Kremsner, Peter G. ;

Lell, Bertrand ;

Owusu-Agyei, Seth ;

Abdulla, Salim .

JOURNAL OF INFECTIOUS DISEASES, 2010, 202 (07) :1076-1087

[4] First Results of Phase 3 Trial of RTS,S/AS01 Malaria Vaccine in African Children [J].

Agnandji, Selidji Todagbe ;

Lell, Bertrand ;

Soulanoudjingar, Solange Solmeheim ;

Fernandes, Jose Francisco ;

Abossolo, Beatrice Peggy ;

Conzelmann, Cornelia ;

Methogo, Barbara Gaelle Nfono Ondo ;

Doucka, Yannick ;

Flamen, Arnaud ;

Mordmueller, Benjamin ;

Issifou, Saadou ;

Kremsner, Peter Gottfried ;

Sacarlal, Jahit ;

Aide, Pedro ;

Lanaspa, Miguel ;

Aponte, John J. ;

Nhamuave, Arlindo ;

Quelhas, Diana ;

Bassat, Quique ;

Mandjate, Sofia ;

Macete, Eusebio ;

Alonso, Pedro ;

Abdulla, Salim ;

Salim, Nahya ;

Juma, Omar ;

Shomari, Mwanajaa ;

Shubis, Kafuruki ;

Machera, Francisca ;

Hamad, Ali Said ;

Minja, Rose ;

Mpina, Maxmillian ;

Mtoro, Ali ;

Sykes, Alma ;

Ahmed, Saumu ;

Urassa, Alwisa Martin ;

Ali, Ali Mohammed ;

Mwangoka, Grace ;

Tanner, Marcel ;

Tinto, Halidou ;

D'Alessandro, Umberto ;

Sorgho, Hermann ;

Valea, Innocent ;

Tahita, Marc Christian ;

Kabore, William ;

Ouedraogo, Sayouba ;

Sandrine, Yara ;

Guiguemde, Robert Tinga ;

Ouedraogo, Jean Bosco ;

Hamel, Mary J. ;

Kariuki, Simon .

NEW ENGLAND JOURNAL OF MEDICINE, 2011, 365 (20) :1863-1875

[5]

[Anonymous], 2004, IMM PRACT MOD 2 EPI, P26

[6]

[Anonymous], 1996, INT C HARM TECHN REQ, P30

[7] 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

[8]

Asante KP, 2011, LANCET INFECT DIS, V11, P727

[9] Rash including mucosal involvement: Case definition and guidelines for collection, analysis, and presentation of immunization safety data [J].

Beigel, John ;

Kohl, Katrin S. ;

Khuri-Bulos, Najwa ;

Bravo, Lulu ;

Nell, Patricia ;

Marcy, S. Michael ;

Warschaw, Karen ;

Ong-Lim, Anna ;

Poerschke, Gabriele ;

Weston, William ;

Lindstrom, Jill A. ;

Stoltman, Gillian ;

Maurer, Toby .

VACCINE, 2007, 25 (31) :5697-5706

[10] Defining childhood severe falciparum malaria for intervention studies [J].

Bejon, Philip ;

Berkley, James A. ;

Mwangi, Tabitha ;

Ogada, Edna ;

Mwangi, Isaiah ;

Maitland, Kathryn ;

Williams, Thomas ;

Scott, J. Anthony G. ;

English, Mike ;

Lowe, Brett S. ;

Peshu, Norbert ;

Newton, Charles R. J. C. ;

Marsh, Kevin .

PLOS MEDICINE, 2007, 4 (08) :1333-1340

← 1 2 3 4 →