BACKGROUND: The RTS,S/AS01 vaccine targets the circumsporozoite protein of Plasmodium falciparum and has partial protective efficacy against clinical and severe malaria disease in infants and children. We investigated whether the vaccine efficacy was specific to certain parasite genotypes at the circumsporozoite protein locus. METHODS: We used polymerase chain reaction-based next-generation sequencing of DNA extracted from samplesfrom 4985 participants to survey circumsporozoite protein polymorphisms. We evaluated the effect that polymorphic positions and haplotypic regions within the circumsporozoite protein had on vaccine efficacy against first episodes of clinical malaria within 1 year after vaccination. RESULTS: In the per-protocol group of 4577 RTS,S/AS01-vaccinated participants and 2335 control-vaccinated participants who were 5 to 17 months of age, the 1-year cumulative vaccine efficacy was 50.3% (95% confidence interval [CI], 34.6 to 62.3) against clinical malaria in which parasites matched the vaccine in the entire circumsporozoite protein C-terminal (139 infections), as compared with 33.4% (95% CI, 29.3 to 37.2) against mismatched malaria (1951 infections) (P=0.04 for differential vaccine efficacy). The vaccine efficacy based on the hazard ratio was 62.7% (95% CI, 51.6 to 71.3) against matched infections versus 54.2% (95% CI, 49.9 to 58.1) against mismatched infections (P=0.06). In the group of infants 6 to 12 weeks of age, there was no evidence of differential allele-specific vaccine efficacy. CONCLUSIONS: These results suggest that among children 5 to 17 months of age, the RTS,S vaccine has greater activity against malaria parasites with the matched circumsporozoite protein allele than against mismatched malaria. The overall vaccine efficacy in this age category will depend on the proportion of matched alleles in the local parasite population; in this trial, less than 10% of parasites had matched alleles. (Funded by the National Institutes of Health and others.).
RCT Entities:
BACKGROUND: The RTS,S/AS01 vaccine targets the circumsporozoite protein of Plasmodium falciparum and has partial protective efficacy against clinical and severe malaria disease in infants and children. We investigated whether the vaccine efficacy was specific to certain parasite genotypes at the circumsporozoite protein locus. METHODS: We used polymerase chain reaction-based next-generation sequencing of DNA extracted from samples from 4985 participants to survey circumsporozoite protein polymorphisms. We evaluated the effect that polymorphic positions and haplotypic regions within the circumsporozoite protein had on vaccine efficacy against first episodes of clinical malaria within 1 year after vaccination. RESULTS: In the per-protocol group of 4577 RTS,S/AS01-vaccinated participants and 2335 control-vaccinated participants who were 5 to 17 months of age, the 1-year cumulative vaccine efficacy was 50.3% (95% confidence interval [CI], 34.6 to 62.3) against clinical malaria in which parasites matched the vaccine in the entire circumsporozoite protein C-terminal (139 infections), as compared with 33.4% (95% CI, 29.3 to 37.2) against mismatched malaria (1951 infections) (P=0.04 for differential vaccine efficacy). The vaccine efficacy based on the hazard ratio was 62.7% (95% CI, 51.6 to 71.3) against matched infections versus 54.2% (95% CI, 49.9 to 58.1) against mismatched infections (P=0.06). In the group of infants 6 to 12 weeks of age, there was no evidence of differential allele-specific vaccine efficacy. CONCLUSIONS: These results suggest that among children 5 to 17 months of age, the RTS,S vaccine has greater activity against malaria parasites with the matched circumsporozoite protein allele than against mismatched malaria. The overall vaccine efficacy in this age category will depend on the proportion of matched alleles in the local parasite population; in this trial, less than 10% of parasites had matched alleles. (Funded by the National Institutes of Health and others.).
Authors: Selidji Todagbe Agnandji; Bertrand Lell; Solange Solmeheim Soulanoudjingar; José Francisco Fernandes; Béatrice Peggy Abossolo; Cornelia Conzelmann; Barbara Gaelle Nfono Ondo Methogo; Yannick Doucka; Arnaud Flamen; Benjamin Mordmüller; Saadou Issifou; Peter Gottfried Kremsner; Jahit Sacarlal; Pedro Aide; Miguel Lanaspa; John J Aponte; Arlindo Nhamuave; Diana Quelhas; Quique Bassat; Sofia Mandjate; Eusébio Macete; Pedro Alonso; Salim Abdulla; Nahya Salim; Omar Juma; Mwanajaa Shomari; Kafuruki Shubis; Francisca Machera; Ali Said Hamad; Rose Minja; Ali Mtoro; Alma Sykes; Saumu Ahmed; Alwisa Martin Urassa; Ali Mohammed Ali; Grace Mwangoka; Marcel Tanner; Halidou Tinto; Umberto D'Alessandro; Hermann Sorgho; Innocent Valea; Marc Christian Tahita; William Kaboré; Sayouba Ouédraogo; Yara Sandrine; Robert Tinga Guiguemdé; Jean Bosco Ouédraogo; Mary J Hamel; Simon Kariuki; Chris Odero; Martina Oneko; Kephas Otieno; Norbert Awino; Jackton Omoto; John Williamson; Vincent Muturi-Kioi; Kayla F Laserson; Laurence Slutsker; Walter Otieno; Lucas Otieno; Otsyula Nekoye; Stacey Gondi; Allan Otieno; Bernhards Ogutu; Ruth Wasuna; Victorine Owira; David Jones; Agnes Akoth Onyango; Patricia Njuguna; Roma Chilengi; Pauline Akoo; Christine Kerubo; Jesse Gitaka; Charity Maingi; Trudie Lang; Ally Olotu; Benjamin Tsofa; Philip Bejon; Norbert Peshu; Kevin Marsh; Seth Owusu-Agyei; Kwaku Poku Asante; Kingsley Osei-Kwakye; Owusu Boahen; Samuel Ayamba; Kingsley Kayan; Ruth Owusu-Ofori; David Dosoo; Isaac Asante; George Adjei; George Adjei; Daniel Chandramohan; Brian Greenwood; John Lusingu; Samwel Gesase; Anangisye Malabeja; Omari Abdul; Hassan Kilavo; Coline Mahende; Edwin Liheluka; Martha Lemnge; Thor Theander; Chris Drakeley; Daniel Ansong; Tsiri Agbenyega; Samuel Adjei; Harry Owusu Boateng; Theresa Rettig; John Bawa; Justice Sylverken; David Sambian; Alex Agyekum; Larko Owusu; Francis Martinson; Irving Hoffman; Tisungane Mvalo; Portia Kamthunzi; Ruthendo Nkomo; Albans Msika; Allan Jumbe; Nelecy Chome; Dalitso Nyakuipa; Joseph Chintedza; W Ripley Ballou; Myriam Bruls; Joe Cohen; Yolanda Guerra; Erik Jongert; Didier Lapierre; Amanda Leach; Marc Lievens; Opokua Ofori-Anyinam; Johan Vekemans; Terrell Carter; Didier Leboulleux; Christian Loucq; Afiya Radford; Barbara Savarese; David Schellenberg; Marla Sillman; Preeti Vansadia Journal: N Engl J Med Date: 2011-10-18 Impact factor: 91.245
Authors: Kent E Kester; James F Cummings; Opokua Ofori-Anyinam; Christian F Ockenhouse; Urszula Krzych; Philippe Moris; Robert Schwenk; Robin A Nielsen; Zufan Debebe; Evgeny Pinelis; Laure Juompan; Jack Williams; Megan Dowler; V Ann Stewart; Robert A Wirtz; Marie-Claude Dubois; Marc Lievens; Joe Cohen; W Ripley Ballou; D Gray Heppner Journal: J Infect Dis Date: 2009-08-01 Impact factor: 5.226
Authors: M F Good; D Pombo; I A Quakyi; E M Riley; R A Houghten; A Menon; D W Alling; J A Berzofsky; L H Miller Journal: Proc Natl Acad Sci U S A Date: 1988-02 Impact factor: 11.205
Authors: Ali Alloueche; Paul Milligan; David J Conway; Margaret Pinder; Kalifa Bojang; Tom Doherty; Nadia Tornieporth; Joe Cohen; Brian M Greenwood Journal: Am J Trop Med Hyg Date: 2003-01 Impact factor: 2.345
Authors: 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; 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 Journal: N Engl J Med Date: 2012-11-09 Impact factor: 91.245
Authors: DeAnna J Friedman-Klabanoff; Matthew B Laurens; Andrea A Berry; Mark A Travassos; Matthew Adams; Kathy A Strauss; Biraj Shrestha; Myron M Levine; Robert Edelman; Kirsten E Lyke Journal: Am J Trop Med Hyg Date: 2019-03 Impact factor: 2.345
Authors: Judith E Epstein; Kristopher M Paolino; Thomas L Richie; Martha Sedegah; Alexandra Singer; Adam J Ruben; Sumana Chakravarty; April Stafford; Richard C Ruck; Abraham G Eappen; Tao Li; Peter F Billingsley; Anita Manoj; Joana C Silva; Kara Moser; Robin Nielsen; Donna Tosh; Susan Cicatelli; Harini Ganeshan; Jessica Case; Debbie Padilla; Silas Davidson; Lindsey Garver; Elizabeth Saverino; Tooba Murshedkar; Anusha Gunasekera; Patrick S Twomey; Sharina Reyes; James E Moon; Eric R James; Natasha Kc; Minglin Li; Esteban Abot; Arnel Belmonte; Kevin Hauns; Maria Belmonte; Jun Huang; Carlos Vasquez; Shon Remich; Mary Carrington; Yonas Abebe; Amy Tillman; Bradley Hickey; Jason Regules; Eileen Villasante; B Kim Lee Sim; Stephen L Hoffman Journal: JCI Insight Date: 2017-01-12
Authors: Joseph R Francica; Daniel E Zak; Caitlyn Linde; Emilio Siena; Carrie Johnson; Michal Juraska; Nicole L Yates; Bronwyn Gunn; Ennio De Gregorio; Barbara J Flynn; Nicholas M Valiante; Padma Malyala; Susan W Barnett; Pampi Sarkar; Manmohan Singh; Siddhartha Jain; Margaret Ackerman; Munir Alam; Guido Ferrari; Andres Salazar; Georgia D Tomaras; Derek T O'Hagan; Alan Aderem; Galit Alter; Robert A Seder Journal: Blood Adv Date: 2017-11-17