A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants

Selidji Todagbe Agnandji, Bertrand Lell, José Francisco Fernandes, Béatrice Peggy Abossolo, Barbara Gaelle Nfono Ondo Methogo, Anita Lumeka Kabwende, Ayola Akim Adegnika, Benjamin Mordmüller, Saadou Issifou, Peter Gottfried Kremsner, Jahit Sacarlal, Pedro Aide, Miguel Lanaspa, John J. Aponte, Sonia Machevo, Sozinho Acacio, Helder Bulo, Betuel Sigauque, Eusébio Macete, Pedro Alonso & 110 others Salim Abdulla, Nahya Salim, Rose Minja, Maxmillian Mpina, Saumu Ahmed, Ali Mohammed Ali, Ali Takadir Mtoro, Ali Said Hamad, Paul Mutani, Marcel Tanner, Halidou Tinto, Umberto D'Alessandro, Hermann Sorgho, Innocent Valea, Biébo Bihoun, Issa Guiraud, Berenger Kaboré, Olivier Sombié, Robert Tinga Guiguemdé, Jean Bosco Ouédraogo, Mary J. Hamel, Simon Kariuki, Martina Oneko, Chris Odero, Kephas Otieno, Norbert Awino, Meredith McMorrow, Vincent Muturi-Kioi, Kayla F. Laserson, Laurence Slutsker, Walter Otieno, Lucas Otieno, Nekoye Otsyula, Stacey Gondi, Allan Otieno, Victorine Owira, Esther Oguk, George Odongo, Jon Ben Woods, Bernhards Ogutu, Patricia Njuguna, Roma Chilengi, Pauline Akoo, Christine Kerubo, Charity Maingi, Trudie Lang, Ally Olotu, Philip Bejon, Kevin Marsh, Gabriel Mwambingu, Seth Owusu-Agyei, Kwaku Poku Asante, Kingsley Osei-Kwakye, Owusu Boahen, David Dosoo, Isaac Asante, George Adjei, Evans Kwara, Daniel Chandramohan, Brian Greenwood, John Lusingu, Samwel Gesase, Anangisye Malabeja, Omari Abdul, Coline Mahende, Edwin Liheluka, Lincoln Malle, Martha Lemnge, Thor G. Theander, Chris Drakeley, Daniel Ansong, Tsiri Agbenyega, Samuel Adjei, Harry Owusu Boateng, Theresa Rettig, John Bawa, Justice Sylverken, David Sambian, Anima Sarfo, Alex Agyekum, Francis Martinson, Irving Hoffman, Tisungane Mvalo, Portia Kamthunzi, Rutendo Nkomo, Tapiwa Tembo, Gerald Tegha, Mercy Tsidya, Jane Kilembe, Chimwemwe Chawinga, W. Ripley Ballou, Joe Cohen, Yolanda Guerra, Erik Jongert, Didier Lapierre, Amanda Leach, Marc Lievens, Opokua Ofori-Anyinam, Aurélie Olivier, Johan Vekemans, Terrell Carter, David Kaslow, Didier Leboulleux, Christian Loucq, Afiya Radford, Barbara Savarese, David Schellenberg, Marla Sillman, Preeti Vansadia, Sara Mian-McCarthy

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Abstract

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 personyear 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.)

Original languageEnglish
Pages (from-to)2284-2295
Number of pages12
JournalNew England Journal of Medicine
Volume367
Issue number24
DOIs
Publication statusPublished - 2012

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Malaria Vaccines
Vaccines
Malaria
Confidence Intervals
Immunization Programs
Population
Vaccination
RTS,S-AS01 vaccine
Anti-Idiotypic Antibodies
Appointments and Schedules
Safety
Control Groups

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Agnandji, S. T., Lell, B., Fernandes, J. F., Abossolo, B. P., Methogo, B. G. N. O., Kabwende, A. L., ... Mian-McCarthy, S. (2012). A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants. New England Journal of Medicine, 367(24), 2284-2295. https://doi.org/10.1056/NEJMoa1208394
Agnandji, Selidji Todagbe ; Lell, Bertrand ; Fernandes, José Francisco ; Abossolo, Béatrice Peggy ; Methogo, Barbara Gaelle Nfono Ondo ; Kabwende, Anita Lumeka ; Adegnika, Ayola Akim ; Mordmüller, Benjamin ; Issifou, Saadou ; Kremsner, Peter Gottfried ; Sacarlal, Jahit ; Aide, Pedro ; Lanaspa, Miguel ; Aponte, John J. ; Machevo, Sonia ; Acacio, Sozinho ; Bulo, Helder ; Sigauque, Betuel ; Macete, Eusébio ; Alonso, Pedro ; Abdulla, Salim ; Salim, Nahya ; Minja, Rose ; Mpina, Maxmillian ; Ahmed, Saumu ; Ali, Ali Mohammed ; Mtoro, Ali Takadir ; Hamad, Ali Said ; Mutani, Paul ; Tanner, Marcel ; Tinto, Halidou ; D'Alessandro, Umberto ; Sorgho, Hermann ; Valea, Innocent ; Bihoun, Biébo ; Guiraud, Issa ; Kaboré, Berenger ; Sombié, Olivier ; Guiguemdé, Robert Tinga ; Ouédraogo, Jean Bosco ; Hamel, Mary J. ; Kariuki, Simon ; Oneko, Martina ; Odero, Chris ; Otieno, Kephas ; Awino, Norbert ; McMorrow, Meredith ; Muturi-Kioi, Vincent ; Laserson, Kayla F. ; Slutsker, Laurence ; Otieno, Walter ; Otieno, Lucas ; Otsyula, Nekoye ; Gondi, Stacey ; Otieno, Allan ; Owira, Victorine ; Oguk, Esther ; Odongo, George ; Ben Woods, Jon ; Ogutu, Bernhards ; Njuguna, Patricia ; Chilengi, Roma ; Akoo, Pauline ; Kerubo, Christine ; Maingi, Charity ; Lang, Trudie ; Olotu, Ally ; Bejon, Philip ; Marsh, Kevin ; Mwambingu, Gabriel ; Owusu-Agyei, Seth ; Asante, Kwaku Poku ; Osei-Kwakye, Kingsley ; Boahen, Owusu ; Dosoo, David ; Asante, Isaac ; Adjei, George ; Kwara, Evans ; Chandramohan, Daniel ; Greenwood, Brian ; Lusingu, John ; Gesase, Samwel ; Malabeja, Anangisye ; Abdul, Omari ; Mahende, Coline ; Liheluka, Edwin ; Malle, Lincoln ; Lemnge, Martha ; Theander, Thor G. ; Drakeley, Chris ; Ansong, Daniel ; Agbenyega, Tsiri ; Adjei, Samuel ; Boateng, Harry Owusu ; Rettig, Theresa ; Bawa, John ; Sylverken, Justice ; Sambian, David ; Sarfo, Anima ; Agyekum, Alex ; Martinson, Francis ; Hoffman, Irving ; Mvalo, Tisungane ; Kamthunzi, Portia ; Nkomo, Rutendo ; Tembo, Tapiwa ; Tegha, Gerald ; Tsidya, Mercy ; Kilembe, Jane ; Chawinga, Chimwemwe ; Ballou, W. Ripley ; Cohen, Joe ; Guerra, Yolanda ; Jongert, Erik ; Lapierre, Didier ; Leach, Amanda ; Lievens, Marc ; Ofori-Anyinam, Opokua ; Olivier, Aurélie ; Vekemans, Johan ; Carter, Terrell ; Kaslow, David ; Leboulleux, Didier ; Loucq, Christian ; Radford, Afiya ; Savarese, Barbara ; Schellenberg, David ; Sillman, Marla ; Vansadia, Preeti ; Mian-McCarthy, Sara. / A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants. In: New England Journal of Medicine. 2012 ; Vol. 367, No. 24. pp. 2284-2295.
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title = "A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants",
abstract = "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 personyear 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.)",
author = "Agnandji, {Selidji Todagbe} and Bertrand Lell and Fernandes, {Jos{\'e} Francisco} and Abossolo, {B{\'e}atrice Peggy} and Methogo, {Barbara Gaelle Nfono Ondo} and Kabwende, {Anita Lumeka} and Adegnika, {Ayola Akim} and Benjamin Mordm{\"u}ller and Saadou Issifou and Kremsner, {Peter Gottfried} and Jahit Sacarlal and Pedro Aide and Miguel Lanaspa and Aponte, {John J.} and Sonia Machevo and Sozinho Acacio and Helder Bulo and Betuel Sigauque and Eus{\'e}bio Macete and Pedro Alonso and Salim Abdulla and Nahya Salim and Rose Minja and Maxmillian Mpina and Saumu Ahmed and Ali, {Ali Mohammed} and Mtoro, {Ali Takadir} and Hamad, {Ali Said} and Paul Mutani and Marcel Tanner and Halidou Tinto and Umberto D'Alessandro and Hermann Sorgho and Innocent Valea and Bi{\'e}bo Bihoun and Issa Guiraud and Berenger Kabor{\'e} and Olivier Sombi{\'e} and Guiguemd{\'e}, {Robert Tinga} and Ou{\'e}draogo, {Jean Bosco} and Hamel, {Mary J.} and Simon Kariuki and Martina Oneko and Chris Odero and Kephas Otieno and Norbert Awino and Meredith McMorrow and Vincent Muturi-Kioi and Laserson, {Kayla F.} and Laurence Slutsker and Walter Otieno and Lucas Otieno and Nekoye Otsyula and Stacey Gondi and Allan Otieno and Victorine Owira and Esther Oguk and George Odongo and {Ben Woods}, Jon and Bernhards Ogutu and Patricia Njuguna and Roma Chilengi and Pauline Akoo and Christine Kerubo and Charity Maingi and Trudie Lang and Ally Olotu and Philip Bejon and Kevin Marsh and Gabriel Mwambingu and Seth Owusu-Agyei and Asante, {Kwaku Poku} and Kingsley Osei-Kwakye and Owusu Boahen and David Dosoo and Isaac Asante and George Adjei and Evans Kwara and Daniel Chandramohan and Brian Greenwood and John Lusingu and Samwel Gesase and Anangisye Malabeja and Omari Abdul and Coline Mahende and Edwin Liheluka and Lincoln Malle and Martha Lemnge and Theander, {Thor G.} and Chris Drakeley and Daniel Ansong and Tsiri Agbenyega and Samuel Adjei and Boateng, {Harry Owusu} and Theresa Rettig and John Bawa and Justice Sylverken and David Sambian and Anima Sarfo and Alex Agyekum and Francis Martinson and Irving Hoffman and Tisungane Mvalo and Portia Kamthunzi and Rutendo Nkomo and Tapiwa Tembo and Gerald Tegha and Mercy Tsidya and Jane Kilembe and Chimwemwe Chawinga and Ballou, {W. Ripley} and Joe Cohen and Yolanda Guerra and Erik Jongert and Didier Lapierre and Amanda Leach and Marc Lievens and Opokua Ofori-Anyinam and Aur{\'e}lie Olivier and Johan Vekemans and Terrell Carter and David Kaslow and Didier Leboulleux and Christian Loucq and Afiya Radford and Barbara Savarese and David Schellenberg and Marla Sillman and Preeti Vansadia and Sara Mian-McCarthy",
year = "2012",
doi = "10.1056/NEJMoa1208394",
language = "English",
volume = "367",
pages = "2284--2295",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachusetts Medical Society",
number = "24",

}

Agnandji, ST, Lell, B, Fernandes, JF, Abossolo, BP, Methogo, BGNO, Kabwende, AL, Adegnika, AA, Mordmüller, B, Issifou, S, Kremsner, PG, Sacarlal, J, Aide, P, Lanaspa, M, Aponte, JJ, Machevo, S, Acacio, S, Bulo, H, Sigauque, B, Macete, E, Alonso, P, Abdulla, S, Salim, N, Minja, R, Mpina, M, Ahmed, S, Ali, AM, Mtoro, AT, Hamad, AS, Mutani, P, Tanner, M, Tinto, H, D'Alessandro, U, Sorgho, H, Valea, I, Bihoun, B, Guiraud, I, Kaboré, B, Sombié, O, Guiguemdé, RT, Ouédraogo, JB, Hamel, MJ, Kariuki, S, Oneko, M, Odero, C, Otieno, K, Awino, N, McMorrow, M, Muturi-Kioi, V, Laserson, KF, Slutsker, L, Otieno, W, Otieno, L, Otsyula, N, Gondi, S, Otieno, A, Owira, V, Oguk, E, Odongo, G, Ben Woods, J, Ogutu, B, Njuguna, P, Chilengi, R, Akoo, P, Kerubo, C, Maingi, C, Lang, T, Olotu, A, Bejon, P, Marsh, K, Mwambingu, G, Owusu-Agyei, S, Asante, KP, Osei-Kwakye, K, Boahen, O, Dosoo, D, Asante, I, Adjei, G, Kwara, E, Chandramohan, D, Greenwood, B, Lusingu, J, Gesase, S, Malabeja, A, Abdul, O, Mahende, C, Liheluka, E, Malle, L, Lemnge, M, Theander, TG, Drakeley, C, Ansong, D, Agbenyega, T, Adjei, S, Boateng, HO, Rettig, T, Bawa, J, Sylverken, J, Sambian, D, Sarfo, A, Agyekum, A, Martinson, F, Hoffman, I, Mvalo, T, Kamthunzi, P, Nkomo, R, Tembo, T, Tegha, G, Tsidya, M, Kilembe, J, Chawinga, C, Ballou, WR, Cohen, J, Guerra, Y, Jongert, E, Lapierre, D, Leach, A, Lievens, M, Ofori-Anyinam, O, Olivier, A, Vekemans, J, Carter, T, Kaslow, D, Leboulleux, D, Loucq, C, Radford, A, Savarese, B, Schellenberg, D, Sillman, M, Vansadia, P & Mian-McCarthy, S 2012, 'A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants', New England Journal of Medicine, vol. 367, no. 24, pp. 2284-2295. https://doi.org/10.1056/NEJMoa1208394

A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants. / Agnandji, Selidji Todagbe; Lell, Bertrand; Fernandes, José Francisco; Abossolo, Béatrice Peggy; Methogo, Barbara Gaelle Nfono Ondo; Kabwende, Anita Lumeka; Adegnika, Ayola Akim; Mordmüller, Benjamin; Issifou, Saadou; Kremsner, Peter Gottfried; Sacarlal, Jahit; Aide, Pedro; Lanaspa, Miguel; Aponte, John J.; Machevo, Sonia; Acacio, Sozinho; Bulo, Helder; Sigauque, Betuel; Macete, Eusébio; Alonso, Pedro; Abdulla, Salim; Salim, Nahya; Minja, Rose; Mpina, Maxmillian; Ahmed, Saumu; Ali, Ali Mohammed; Mtoro, Ali Takadir; Hamad, Ali Said; Mutani, Paul; Tanner, Marcel; Tinto, Halidou; D'Alessandro, Umberto; Sorgho, Hermann; Valea, Innocent; Bihoun, Biébo; Guiraud, Issa; Kaboré, Berenger; Sombié, Olivier; Guiguemdé, Robert Tinga; Ouédraogo, Jean Bosco; Hamel, Mary J.; Kariuki, Simon; Oneko, Martina; Odero, Chris; Otieno, Kephas; Awino, Norbert; McMorrow, Meredith; Muturi-Kioi, Vincent; Laserson, Kayla F.; Slutsker, Laurence; Otieno, Walter; Otieno, Lucas; Otsyula, Nekoye; Gondi, Stacey; Otieno, Allan; Owira, Victorine; Oguk, Esther; Odongo, George; Ben Woods, Jon; Ogutu, Bernhards; Njuguna, Patricia; Chilengi, Roma; Akoo, Pauline; Kerubo, Christine; Maingi, Charity; Lang, Trudie; Olotu, Ally; Bejon, Philip; Marsh, Kevin; Mwambingu, Gabriel; Owusu-Agyei, Seth; Asante, Kwaku Poku; Osei-Kwakye, Kingsley; Boahen, Owusu; Dosoo, David; Asante, Isaac; Adjei, George; Kwara, Evans; Chandramohan, Daniel; Greenwood, Brian; Lusingu, John; Gesase, Samwel; Malabeja, Anangisye; Abdul, Omari; Mahende, Coline; Liheluka, Edwin; Malle, Lincoln; Lemnge, Martha; Theander, Thor G.; Drakeley, Chris; Ansong, Daniel; Agbenyega, Tsiri; Adjei, Samuel; Boateng, Harry Owusu; Rettig, Theresa; Bawa, John; Sylverken, Justice; Sambian, David; Sarfo, Anima; Agyekum, Alex; Martinson, Francis; Hoffman, Irving; Mvalo, Tisungane; Kamthunzi, Portia; Nkomo, Rutendo; Tembo, Tapiwa; Tegha, Gerald; Tsidya, Mercy; Kilembe, Jane; Chawinga, Chimwemwe; Ballou, W. Ripley; Cohen, Joe; Guerra, Yolanda; Jongert, Erik; Lapierre, Didier; Leach, Amanda; Lievens, Marc; Ofori-Anyinam, Opokua; Olivier, Aurélie; Vekemans, Johan; Carter, Terrell; Kaslow, David; Leboulleux, Didier; Loucq, Christian; Radford, Afiya; Savarese, Barbara; Schellenberg, David; Sillman, Marla; Vansadia, Preeti; Mian-McCarthy, Sara.

In: New England Journal of Medicine, Vol. 367, No. 24, 2012, p. 2284-2295.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants

AU - Agnandji, Selidji Todagbe

AU - Lell, Bertrand

AU - Fernandes, José Francisco

AU - Abossolo, Béatrice Peggy

AU - Methogo, Barbara Gaelle Nfono Ondo

AU - Kabwende, Anita Lumeka

AU - Adegnika, Ayola Akim

AU - Mordmüller, Benjamin

AU - Issifou, Saadou

AU - Kremsner, Peter Gottfried

AU - Sacarlal, Jahit

AU - Aide, Pedro

AU - Lanaspa, Miguel

AU - Aponte, John J.

AU - Machevo, Sonia

AU - Acacio, Sozinho

AU - Bulo, Helder

AU - Sigauque, Betuel

AU - Macete, Eusébio

AU - Alonso, Pedro

AU - Abdulla, Salim

AU - Salim, Nahya

AU - Minja, Rose

AU - Mpina, Maxmillian

AU - Ahmed, Saumu

AU - Ali, Ali Mohammed

AU - Mtoro, Ali Takadir

AU - Hamad, Ali Said

AU - Mutani, Paul

AU - Tanner, Marcel

AU - Tinto, Halidou

AU - D'Alessandro, Umberto

AU - Sorgho, Hermann

AU - Valea, Innocent

AU - Bihoun, Biébo

AU - Guiraud, Issa

AU - Kaboré, Berenger

AU - Sombié, Olivier

AU - Guiguemdé, Robert Tinga

AU - Ouédraogo, Jean Bosco

AU - Hamel, Mary J.

AU - Kariuki, Simon

AU - Oneko, Martina

AU - Odero, Chris

AU - Otieno, Kephas

AU - Awino, Norbert

AU - McMorrow, Meredith

AU - Muturi-Kioi, Vincent

AU - Laserson, Kayla F.

AU - Slutsker, Laurence

AU - Otieno, Walter

AU - Otieno, Lucas

AU - Otsyula, Nekoye

AU - Gondi, Stacey

AU - Otieno, Allan

AU - Owira, Victorine

AU - Oguk, Esther

AU - Odongo, George

AU - Ben Woods, Jon

AU - Ogutu, Bernhards

AU - Njuguna, Patricia

AU - Chilengi, Roma

AU - Akoo, Pauline

AU - Kerubo, Christine

AU - Maingi, Charity

AU - Lang, Trudie

AU - Olotu, Ally

AU - Bejon, Philip

AU - Marsh, Kevin

AU - Mwambingu, Gabriel

AU - Owusu-Agyei, Seth

AU - Asante, Kwaku Poku

AU - Osei-Kwakye, Kingsley

AU - Boahen, Owusu

AU - Dosoo, David

AU - Asante, Isaac

AU - Adjei, George

AU - Kwara, Evans

AU - Chandramohan, Daniel

AU - Greenwood, Brian

AU - Lusingu, John

AU - Gesase, Samwel

AU - Malabeja, Anangisye

AU - Abdul, Omari

AU - Mahende, Coline

AU - Liheluka, Edwin

AU - Malle, Lincoln

AU - Lemnge, Martha

AU - Theander, Thor G.

AU - Drakeley, Chris

AU - Ansong, Daniel

AU - Agbenyega, Tsiri

AU - Adjei, Samuel

AU - Boateng, Harry Owusu

AU - Rettig, Theresa

AU - Bawa, John

AU - Sylverken, Justice

AU - Sambian, David

AU - Sarfo, Anima

AU - Agyekum, Alex

AU - Martinson, Francis

AU - Hoffman, Irving

AU - Mvalo, Tisungane

AU - Kamthunzi, Portia

AU - Nkomo, Rutendo

AU - Tembo, Tapiwa

AU - Tegha, Gerald

AU - Tsidya, Mercy

AU - Kilembe, Jane

AU - Chawinga, Chimwemwe

AU - Ballou, W. Ripley

AU - Cohen, Joe

AU - Guerra, Yolanda

AU - Jongert, Erik

AU - Lapierre, Didier

AU - Leach, Amanda

AU - Lievens, Marc

AU - Ofori-Anyinam, Opokua

AU - Olivier, Aurélie

AU - Vekemans, Johan

AU - Carter, Terrell

AU - Kaslow, David

AU - Leboulleux, Didier

AU - Loucq, Christian

AU - Radford, Afiya

AU - Savarese, Barbara

AU - Schellenberg, David

AU - Sillman, Marla

AU - Vansadia, Preeti

AU - Mian-McCarthy, Sara

PY - 2012

Y1 - 2012

N2 - 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 personyear 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.)

AB - 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 personyear 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.)

UR - http://www.scopus.com/inward/record.url?scp=84871037616&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa1208394

DO - 10.1056/NEJMoa1208394

M3 - Article

VL - 367

SP - 2284

EP - 2295

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 24

ER -

Agnandji ST, Lell B, Fernandes JF, Abossolo BP, Methogo BGNO, Kabwende AL et al. A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants. New England Journal of Medicine. 2012;367(24):2284-2295. https://doi.org/10.1056/NEJMoa1208394