First Results of Phase 3 Trial of RTS,S/AS01 Malaria Vaccine in African Children

被引：645

作者：

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

Lell, Bertrand ^{[1
,2
]}

Soulanoudjingar, Solange Solmeheim ^{[1
,2
]}

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

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

Conzelmann, Cornelia ^{[1
,2
]}

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

Doucka, Yannick ^{[1
,2
]}

Flamen, Arnaud ^{[1
,2
]}

Mordmueller, Benjamin ^{[1
,2
]}

Issifou, Saadou ^{[1
,2
]}

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

Sacarlal, Jahit ^{[3
]}

Aide, Pedro ^{[3
]}

Lanaspa, Miguel ^{[3
]}

Aponte, John J. ^{[3
]}

Nhamuave, Arlindo ^{[3
]}

Quelhas, Diana ^{[3
]}

Bassat, Quique ^{[3
]}

Mandjate, Sofia ^{[3
]}

Macete, Eusebio ^{[3
]}

Alonso, Pedro ^{[3
]}

Abdulla, Salim ^{[4
]}

Salim, Nahya ^{[4
]}

Juma, Omar ^{[4
]}

Shomari, Mwanajaa ^{[4
]}

Shubis, Kafuruki ^{[4
]}

Machera, Francisca ^{[4
]}

Hamad, Ali Said ^{[4
]}

Minja, Rose ^{[4
]}

Mpina, Maxmillian ^{[4
]}

Mtoro, Ali ^{[4
]}

Sykes, Alma ^{[4
]}

Ahmed, Saumu ^{[4
]}

Urassa, Alwisa Martin ^{[4
]}

Ali, Ali Mohammed ^{[4
]}

Mwangoka, Grace ^{[4
]}

Tanner, Marcel ^{[4
]}

Tinto, Halidou ^{[5
]}

D'Alessandro, Umberto ^{[5
]}

Sorgho, Hermann ^{[5
]}

Valea, Innocent ^{[5
]}

Tahita, Marc Christian ^{[5
]}

Kabore, William ^{[5
]}

Ouedraogo, Sayouba ^{[5
]}

Sandrine, Yara ^{[5
]}

Guiguemde, Robert Tinga ^{[5
]}

Ouedraogo, Jean Bosco ^{[5
]}

Hamel, Mary J. ^{[6
]}

Kariuki, Simon ^{[6
]}

机构：

[1] Albert Schweitzer Hosp, Lambarene, Gabon

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

[3] Ctr Invest Saude Manhica, Manhica, Mozambique

[4] Ifakara Hlth Inst, Bagamoyo, Tanzania

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

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

[7] KEMRI Walter Reed Project, Kombewa, Kenya

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

[9] Kintampo Hlth Res Ctr, Kintampo, Ghana

[10] Natl Inst Med Res, Korogwe, Tanzania

[11] Sch Med Sci, Kumasi, Ghana

[12] Univ N Carolina Project, Lilongwe, Malawi

[13] GlaxoSmithKline Inc, Wavre, Belgium

[14] PATH Malaria Vaccine Initiat, Washington, DC USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2011年 / 365卷 / 20期

关键词：

PLASMODIUM-FALCIPARUM INFECTION; III MULTICENTER TRIAL; MOZAMBICAN CHILDREN; CANDIDATE VACCINE; EXPANDED-PROGRAM; EFFICACY; SAFETY; IMMUNIZATION; IMMUNOGENICITY; INFANTS;

D O I：

10.1056/NEJMoa1102287

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

BACKGROUND An ongoing phase 3 study of the efficacy, safety, and immunogenicity of candidate malaria vaccine RTS,S/AS01 is being conducted in seven African countries. METHODS From March 2009 through January 2011, we enrolled 15,460 children in two age categories - 6 to 12 weeks of age and 5 to 17 months of age - for vaccination with either RTS,S/AS01 or a non-malaria comparator vaccine. The primary end point of the analysis was vaccine efficacy against clinical malaria during the 12 months after vaccination in the first 6000 children 5 to 17 months of age at enrollment who received all three doses of vaccine according to protocol. After 250 children had an episode of severe malaria, we evaluated vaccine efficacy against severe malaria in both age categories. RESULTS In the 14 months after the first dose of vaccine, the incidence of first episodes of clinical malaria in the first 6000 children in the older age category was 0.32 episodes per person-year in the RTS, S/AS01 group and 0.55 episodes per person-year in the control group, for an efficacy of 50.4% (95% confidence interval [CI], 45.8 to 54.6) in the intention-to-treat population and 55.8% (97.5% CI, 50.6 to 60.4) in the per-protocol population. Vaccine efficacy against severe malaria was 45.1% (95% CI, 23.8 to 60.5) in the intention-to-treat population and 47.3% (95% CI, 22.4 to 64.2) in the per-protocol population. Vaccine efficacy against severe malaria in the combined age categories was 34.8% (95% CI, 16.2 to 49.2) in the per-protocol population during an average follow-up of 11 months. Serious adverse events occurred with a similar frequency in the two study groups. Among children in the older age category, the rate of generalized convulsive seizures after RTS,S/AS01 vaccination was 1.04 per 1000 doses (95% CI, 0.62 to 1.64). CONCLUSIONS The RTS,S/AS01 vaccine provided protection against both clinical and severe malaria in African children. (Funded by GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative; RTS, S

引用

页码：1863 / 1875

页数：13

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