Publications

@article{Datoo2024,

title = {Safety and efficacy of malaria vaccine candidate R21/Matrix-M in African children: a multicentre, double-blind, randomised, phase 3 trial},

author = {Mehreen S. Datoo and Alassane Dicko and Halidou Tinto and Jean Bosco Ou\'{e}draogo and Mainga Hamaluba and Ally Olotu and Emma Beaumont and Fernando Ramos Lopez and Hamtandi Magloire Natama and Sophie Weston and Mwajuma Chemba and Yves Daniel Compaore and Djibrilla Issiaka and Diallo Salou and Athanase M. Some and Sharon Omenda and Alison Lawrie and Philip Bejon and Harish Rao and Daniel Chandramohan and Rachel Roberts and Sandesh Bharati and Lisa Stockdale and Sunil Gairola and Brian M. Greenwood and Katie J. Ewer and John Bradley and Prasad S. Kulkarni and Umesh Shaligram and Adrian V. S. Hill and Almahamoudou Mahamar and Koualy Sanogo and Youssoufa Sidibe and Kalifa Diarra and Mamoudou Samassekou and Oumar Attaher and Amadou Tapily and Makonon Diallo and Oumar Mohamed Dicko and Mahamadou Kaya and Seydina Oumar Maguiraga and Yaya Sankare and Hama Yalcouye and Soumaila Diarra and Sidi Mohamed Niambele and Ismaila Thera and Issaka Sagara and Mala Sylla and Amagana Dolo and Nsajigwa Misidai and Sylvester Simando and Hania Msami and Omary Juma and Nicolaus Gutapaka and Rose Paul and Sarah Mswata and Ibrahim Sasamalo and Kasmir Johaness and Mwantumu Sultan and Annastazia Alexander and Isaac Kimaro and Kauye Lwanga and Mwajuma Mtungwe and Kassim Khamis and Lighton Rugarabam and Wilmina Kalinga and Mohammed Mohammed and Janeth Kamange and Jubilate Msangi and Batuli Mwaijande and Ivanny Mtaka and Matilda Mhapa and Tarsis Mlaganile and Thabit Mbaga and Rakiswende Serge Yerbanga and Wendkouni Samtouma and Abdoul Aziz Sienou and Zachari Kabre and Wendinpui Jedida Muriel Ouedraogo and G. Armel Bienvenu Yarbanga and Issaka Zongo and Hamade Savadogo and Joseph Sanon and Judicael Compaore and Idrissa Kere and Ferdinand Lionel Yoni and Tewende Martine Sanre and Seydou Bienvenu Ouattara and Samuel Provstgaard-Morys and Danielle Woods and Robert W. Snow and Nyaguara Amek and Caroline J. Ngetsa and Lynette Isabella Ochola-Oyier and Jennifer Musyoki and Marianne Munene and Noni Mumba and Uche Jane Adetifa and Charles Mwangi Muiruri and Jimmy Shangala Mwawaka and Mwatasa Hussein Mwaganyuma and Martha Njeri Ndichu and Joseph Ochieng Weya and Kelvin Njogu and Jane Grant and Jayne Webster and Anand Lakhkar and N. F\'{e}lix Andr\'{e} Ido and Ousmane Traore and Marc Christian Tahita and Massa Achille Bonko and Toussaint Rouamba and D. Florence Ouedraogo and Rachidatou Soma and Aida Millogo and Edouard Ouedraogo and Faizatou Sorgho and Fab\'{e} Konate and Innocent Valea},

url = {https://pubmed.ncbi.nlm.nih.gov/38310910/},

doi = {10.1016/S0140-6736(23)02511-4},

issn = {1474-547X},

year  = {2024},

date = {2024-01-01},

journal = {Lancet (London, England)},

volume = {403},

issue = {10426},

pages = {533-544},

publisher = {Lancet},

abstract = {Background: Recently, we found that a new malaria vaccine, R21/Matrix-M, had over 75% efficacy against clinical malaria with seasonal administration in a phase 2b trial in Burkina Faso. Here, we report on safety and efficacy of the vaccine in a phase 3 trial enrolling over 4800 children across four countries followed for up to 18 months at seasonal sites and 12 months at standard sites. Methods: We did a double-blind, randomised, phase 3 trial of the R21/Matrix-M malaria vaccine across five sites in four African countries with differing malaria transmission intensities and seasonality. Children (aged 5\textendash36 months) were enrolled and randomly assigned (2:1) to receive 5 μg R21 plus 50 μg Matrix-M or a control vaccine (licensed rabies vaccine [Abhayrab]). Participants, their families, investigators, laboratory teams, and the local study team were masked to treatment. Vaccines were administered as three doses, 4 weeks apart, with a booster administered 12 months after the third dose. Half of the children were recruited at two sites with seasonal malaria transmission and the remainder at standard sites with perennial malaria transmission using age-based immunisation. The primary objective was protective efficacy of R21/Matrix-M from 14 days after third vaccination to 12 months after completion of the primary series at seasonal and standard sites separately as co-primary endpoints. Vaccine efficacy against multiple malaria episodes and severe malaria, as well as safety and immunogenicity, were also assessed. This trial is registered on ClinicalTrials.gov, NCT04704830, and is ongoing. Findings: From April 26, 2021, to Jan 12, 2022, 5477 children consented to be screened, of whom 1705 were randomly assigned to control vaccine and 3434 to R21/Matrix-M; 4878 participants received the first dose of vaccine. 3103 participants in the R21/Matrix-M group and 1541 participants in the control group were included in the modified per-protocol analysis (2412 [51·9%] male and 2232 [48·1%] female). R21/Matrix-M vaccine was well tolerated, with injection site pain (301 [18·6%] of 1615 participants) and fever (754 [46·7%] of 1615 participants) as the most frequent adverse events. Number of adverse events of special interest and serious adverse events did not significantly differ between the vaccine groups. There were no treatment-related deaths. 12-month vaccine efficacy was 75% (95% CI 71\textendash79; p\<0·0001) at the seasonal sites and 68% (61\textendash74; p\<0·0001) at the standard sites for time to first clinical malaria episode. Similarly, vaccine efficacy against multiple clinical malaria episodes was 75% (71\textendash78; p\<0·0001) at the seasonal sites and 67% (59\textendash73; p\<0·0001) at standard sites. A modest reduction in vaccine efficacy was observed over the first 12 months of follow-up, of similar size at seasonal and standard sites. A rate reduction of 868 (95% CI 762\textendash974) cases per 1000 children-years at seasonal sites and 296 (231\textendash362) at standard sites occurred over 12 months. Vaccine-induced antibodies against the conserved central Asn-Ala-Asn-Pro (NANP) repeat sequence of circumsporozoite protein correlated with vaccine efficacy. Higher NANP-specific antibody titres were observed in the 5\textendash17 month age group compared with 18\textendash36 month age group, and the younger age group had the highest 12-month vaccine efficacy on time to first clinical malaria episode at seasonal (79% [95% CI 73\textendash84]; p\<0·001) and standard (75% [65\textendash83]; p\<0·001) sites. Interpretation: R21/Matrix-M was well tolerated and offered high efficacy against clinical malaria in African children. This low-cost, high-efficacy vaccine is already licensed by several African countries, and recently received a WHO policy recommendation and prequalification, offering large-scale supply to help reduce the great burden of malaria in sub-Saharan Africa. Funding: The Serum Institute of India, the Wellcome Trust, the UK National Institute for Health Research Oxford Biomedical Research Centre, and Open Philanthropy.},

keywords = {{Alassane Dicko, Antibodies, Burkina Faso, Child, Clinical Trial, Double-Blind Method, Female, Humans, Immunization, Infant, Malaria Vaccines* / adverse effects, Malaria* / drug therapy, Male, MEDLINE, Mehreen S Datoo, Multicenter Study, Nanoparticles*, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Non-U.S. Gov't, Phase III, Preschool, PubMed Abstract, Randomized controlled trial, Research Support, Saponins*},

pubstate = {published},

tppubtype = {article}

}

@article{Barry2024,

title = {Helminth exposure and immune response to the two-dose heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen},

author = {Houreratou Barry and Edouard Lhomme and Mathieu Sur\'{e}naud and Moumini Nouctara and Cynthia Robinson and Viki Bockstal and Innocent Valea and Serge Somda and Halidou Tinto and Nicolas Meda and Brian Greenwood and Rodolphe Thi\'{e}baut and Christine Lacabaratz},

url = {https://pubmed.ncbi.nlm.nih.gov/38603720/},

doi = {10.1371/JOURNAL.PNTD.0011500},

issn = {1935-2735},

year  = {2024},

date = {2024-01-01},

journal = {PLoS neglected tropical diseases},

volume = {18},

issue = {4},

publisher = {PLoS Negl Trop Dis},

abstract = {Background The exposure to parasites may influence the immune response to vaccines in endemic African countries. In this study, we aimed to assess the association between helminth exposure to the most prevalent parasitic infections, schistosomiasis, soil transmitted helminths infection and filariasis, and the Ebola virus glycoprotein (EBOV GP) antibody concentration in response to vaccination with the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen in African and European participants using samples obtained from three international clinical trials. Methods/Principal findings We conducted a study in a subset of participants in the EBL2001, EBL2002 and EBL3001 clinical trials that evaluated the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen against EVD in children, adolescents and adults from the United Kingdom, France, Burkina Faso, Cote d’Ivoire, Kenya, Uganda and Sierra Leone. Immune markers of helminth exposure at baseline were evaluated by ELISA with three commercial kits which detect IgG antibodies against schistosome, filarial and Strongyloides antigens. Luminex technology was used to measure inflammatory and activation markers, and Th1/Th2/Th17 cytokines at baseline. The association between binding IgG antibodies specific to EBOV GP (measured on day 21 post-dose 2 and on Day 365 after the first dose respectively), and helminth exposure at baseline was evaluated using a multivariable linear regression model adjusted for age and study group. Seventy-eight (21.3%) of the 367 participants included in the study had at least one helminth positive ELISA test at baseline, with differences of prevalence between studies and an increased prevalence with age. The most frequently detected antibodies were those to Schistosoma mansoni (10.9%), followed by Acanthocheilonema viteae (9%) and then Strongyloides ratti (7.9%). Among the 41 immunological analytes tested, five were significantly (p \< .003) lower in participants with at least one positive helminth ELISA test result: CCL2/MCP1, FGFbasic, IL-7, IL-13 and CCL11/Eotaxin compared to participants with negative helminth ELISA tests. No significant association was found with EBOV-GP specific antibody concentration at 21 days post-dose 2, or at 365 days post-dose 1, adjusted for age group, study, and the presence of any helminth antibodies at baseline. Conclusions/Significance No clear association was found between immune markers of helminth exposure as measured by ELISA and post-vaccination response to the Ebola Ad26.ZEBOV/ MVA-BN-Filo vaccine regimen. Trial registration NCT02416453, NCT02564523, NCT02509494. ClinicalTrials.gov.},

keywords = {Adolescent, Adult, Africa, Aged, Animals, Antibodies, Child, Christine Lacabaratz, Cytokines / immunology, doi:10.1371/journal.pntd.0011500, Ebola Vaccines* / administration \& dosage, Ebola Vaccines* / immunology, Ebola* / immunology, Ebola* / prevention \& control, Ebolavirus / genetics, Ebolavirus / immunology, Edouard Lhomme, Enzyme-Linked Immunosorbent Assay, Female, Helminth / blood, Helminthiasis / immunology, Helminthiasis / prevention \& control, Helminths / genetics, Helminths / immunology, Hemorrhagic Fever, Houreratou Barry, Humans, Immunoglobulin G / blood, Male, MEDLINE, Middle Aged, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Non-U.S. Gov't, PMC11037528, pmid:38603720, Preschool, PubMed Abstract, Research Support, Viral* / blood, Young Adult},

pubstate = {published},

tppubtype = {article}

}

@article{Schmit2024,

title = {The public health impact and cost-effectiveness of the R21/Matrix-M malaria vaccine: a mathematical modelling study},

author = {Nora Schmit and Hillary M. Topazian and H. Magloire Natama and Duncan Bellamy and Ousmane Traor\'{e} and M. Athanase Som\'{e} and Toussaint Rouamba and Marc Christian Tahita and Massa Achille Bonko and Aboubakary Sourabi\'{e} and Hermann Sorgho and Lisa Stockdale and Samuel Provstgaard-Morys and Jeremy Aboagye and Danielle Woods and Katerina Rapi and Mehreen S. Datoo and Fernando Ramos Lopez and Giovanni D. Charles and Kelly McCain and Jean Bosco Ouedraogo and Mainga Hamaluba and Ally Olotu and Alassane Dicko and Halidou Tinto and Adrian V. S. Hill and Katie J. Ewer and Azra C. Ghani and Peter Winskill},

url = {https://pubmed.ncbi.nlm.nih.gov/38342107/},

doi = {10.1016/S1473-3099(23)00816-2},

issn = {1474-4457},

year  = {2024},

date = {2024-01-01},

journal = {The Lancet. Infectious diseases},

volume = {24},

issue = {5},

pages = {465-475},

publisher = {Lancet Infect Dis},

abstract = {Background: The R21/Matrix-M vaccine has demonstrated high efficacy against Plasmodium falciparum clinical malaria in children in sub-Saharan Africa. Using trial data, we aimed to estimate the public health impact and cost-effectiveness of vaccine introduction across sub-Saharan Africa. Methods: We fitted a semi-mechanistic model of the relationship between anti-circumsporozoite protein antibody titres and vaccine efficacy to data from 3 years of follow-up in the phase 2b trial of R21/Matrix-M in Nanoro, Burkina Faso. We validated the model by comparing predicted vaccine efficacy to that observed over 12\textendash18 months in the phase 3 trial. Integrating this framework within a mathematical transmission model, we estimated the cases, malaria deaths, and disability-adjusted life-years (DALYs) averted and cost-effectiveness over a 15-year time horizon across a range of transmission settings in sub-Saharan Africa. Cost-effectiveness was estimated incorporating the cost of vaccine introduction (dose, consumables, and delivery) relative to existing interventions at baseline. We report estimates at a median of 20% parasite prevalence in children aged 2\textendash10 years (PfPR2\textendash10) and ranges from 3% to 65% PfPR2\textendash10. Findings: Anti-circumsporozoite protein antibody titres were found to satisfy the criteria for a surrogate of protection for vaccine efficacy against clinical malaria. Age-based implementation of a four-dose regimen of R21/Matrix-M vaccine was estimated to avert 181 825 (range 38 815\textendash333 491) clinical cases per 100 000 fully vaccinated children in perennial settings and 202 017 (29 868\textendash405 702) clinical cases per 100 000 fully vaccinated children in seasonal settings. Similar estimates were obtained for seasonal or hybrid implementation. Under an assumed vaccine dose price of US$3, the incremental cost per clinical case averted was $7 (range 4\textendash48) in perennial settings and $6 (3\textendash63) in seasonal settings and the incremental cost per DALY averted was $34 (29\textendash139) in perennial settings and $30 (22\textendash172) in seasonal settings, with lower cost-effectiveness ratios in settings with higher PfPR2\textendash10. Interpretation: Introduction of the R21/Matrix-M malaria vaccine could have a substantial public health benefit across sub-Saharan Africa. Funding: The Wellcome Trust, the Bill \& Melinda Gates Foundation, the UK Medical Research Council, the European and Developing Countries Clinical Trials Partnership 2 and 3, the NIHR Oxford Biomedical Research Centre, and the Serum Institute of India, Open Philanthropy.},

keywords = {Antibodies, Burkina Faso / epidemiology, Child, Cost-Benefit Analysis*, Falciparum* / economics, Falciparum* / epidemiology, Falciparum* / prevention \& control, Female, Hillary M Topazian, Humans, Infant, Malaria, Malaria Vaccines* / administration \& dosage, Malaria Vaccines* / economics, Malaria Vaccines* / immunology, Male, MEDLINE, Models, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, Non-U.S. Gov't, Nora Schmit, Peter Winskill, Plasmodium falciparum / immunology, pmid:38342107, Preschool, Protozoan / blood, Protozoan Proteins / immunology, Public Health* / economics, PubMed Abstract, Research Support, Theoretical*, Vaccine Efficacy},

pubstate = {published},

tppubtype = {article}

}

@article{Natama2023,

title = {Associations between prenatal malaria exposure, maternal antibodies at birth, and malaria susceptibility during the first year of life in Burkina Faso},

author = {Hamtandi Magloire Natama and Gemma Moncunill and Marta Vidal and Toussaint Rouamba and Ruth Aguilar and Rebeca Santano and Eduard Rovira-Vallbona and Alfons Jim\'{e}nez and M. Athanase Som\'{e} and Hermann Sorgho and Innocent Val\'{e}a and Maminata Coulibaly-Traor\'{e} and Ross L. Coppel and David Cavanagh and Chetan E. Chitnis and James G. Beeson and Evelina Angov and Sheetij Dutta and Benoit Gamain and Luis Izquierdo and Petra F. Mens and Henk D. F. H. Schallig and Halidou Tinto and Anna Rosanas-Urgell and Carlota Doba\~{n}o},

url = {https://pubmed.ncbi.nlm.nih.gov/37754682/},

doi = {10.1128/IAI.00268-23},

issn = {1098-5522},

year  = {2023},

date = {2023-01-01},

journal = {Infection and immunity},

volume = {91},

issue = {10},

pages = {290},

publisher = {Infect Immun},

abstract = {In this study, we investigated how different categories of prenatal malaria exposure (PME) influence levels of maternal antibodies in cord blood samples and the subsequent risk of malaria in early childhood in a birth cohort study (N = 661) nested within the COSMIC clinical trial (NCT01941264) in Burkina Faso. Plasmodium falciparum infections during pregnancy and infants’ clinical malaria episodes detected during the first year of life were recorded. The levels of maternal IgG and IgG1-4 to 15 P. falciparum antigens were measured in cord blood by quantitative suspension array technology. Results showed a significant variation in the magnitude of maternal antibody levels in cord blood, depending on the PME category, with past placental malaria (PM) more frequently associated with significant increases of IgG and/or subclass levels across three groups of antigens defined as pre-erythrocytic, erythrocytic, and markers of PM, as compared to those from the cord of non-exposed control infants. High levels of antibodies to certain erythrocytic antigens (i.e., IgG to EBA140 and EBA175, IgG1 to EBA175 and MSP142, and IgG3 to EBA140 and MSP5) were independent predictors of protection from clinical malaria during the first year of life. By contrast, high levels of IgG, IgG1, and IgG2 to the VAR2CSA DBL1-2 and IgG4 to DBL3-4 were significantly associated with an increased risk of clinical malaria. These findings indicate that PME categories have different effects on the levels of maternal-derived antibodies to malaria antigens in children at birth, and this might drive heterogeneity to clinical malaria susceptibility in early childhood.},

keywords = {Antibodies, Antigens, Burkina Faso / epidemiology, Carlota Doba\~{n}o, Child, Cohort Studies, doi:10.1128/iai.00268-23, Falciparum*, Female, Gemma Moncunill, Hamtandi Magloire Natama, Humans, Immunoglobulin G, Infant, Malaria, Malaria* / epidemiology, Maternal Exposure, MEDLINE, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, Newborn, NIH, NLM, placenta, Plasmodium falciparum, PMC10580994, pmid:37754682, Pregnancy, Preschool, Protozoan, PubMed Abstract},

pubstate = {published},

tppubtype = {article}

}

@article{Ouedraogo2023,

title = {The burden of the coronavirus disease 2019 virus infection in Burkina Faso: Results from a World Health Organization UNITY population-based, age-stratified sero-epidemiological investigation},

author = {Samiratou Ouedraogo and Isidore Tiandiogo Traor\'{e} and Dramane Kania and Nongodo Firmin Kabor\'{e} and Ariane Mamguem Kamga and Hermann Badolo and Mimbour\'{e} Yara and Guillaume Sanou and Amariane Kon\'{e} and Samdapawind\'{e} Th\'{e}r\`{e}se Kagon\'{e} and Esperance Ou\'{e}draogo and Blahima Konat\'{e} and Rachel M\'{e}dah and Nathalie Rekeneire and Armel Poda and Arnaud Eric Diendere and Boukary Ou\'{e}draogo and Oumar Billa and Gilles Paradis and Halidou Tinto and Tienhan Sandrine Dabakuyo-Yonli},

url = {https://pubmed.ncbi.nlm.nih.gov/38019697/},

doi = {10.1111/IRV.13216},

issn = {1750-2659},

year  = {2023},

date = {2023-01-01},

journal = {Influenza and other respiratory viruses},

volume = {17},

issue = {11},

publisher = {Influenza Other Respir Viruses},

abstract = {Background: This study aimed to estimate the anti-SARS-CoV-2 antibody seroprevalence in the general population of Bobo-Dioulasso and Ouagadougou (Burkina Faso). Methods: We collected from March to April 2021 blood samples from randomly selected residents in both main cities based on the World Health Organization (WHO) sero-epidemiological investigations protocols and tested them with WANTAI SARS-CoV-2 total antibodies enzyme-linked immunosorbent assay (ELISA) kits intended for qualitative assessment. We also recorded participants' socio-demographic and clinical characteristics and information on exposure to SARS-CoV-2. Data were analysed with descriptive and comparative statistics. Results: We tested 5240 blood samples collected between 03 March and 16 April 2021. The overall test-adjusted seroprevalence for SARS-CoV-2 antibodies was (67.8% [95% CI 65.9\textendash70.2]) (N = 3553/3982). Seroprevalence was highest among participants aged 15\textendash18 years old (74.2% [95% CI 70.5\textendash77.5]) (N = 465/627), compared with those aged 10\textendash14 years old (62.6% [95% CI 58.7\textendash66.4]) (N = 395/631), or those over 18 (67.6% [95% CI 66.2\textendash69.1]) (N = 2693/3982). Approximately 71.0% (601/860) of participants aged 10\textendash18 years old who tested positive for SARS-CoV-2 antibodies experienced no clinical COVID-19 symptoms in the weeks before the survey, compared with 39.3% (1059/2693) among those aged over 18 years old. Conclusion: This study reports the results of the first known large serological survey in the general population of Burkina Faso. It shows high circulation of SARS-CoV-2 in the two cities and a high proportion of asymptomatic adolescents. Further studies are needed to identify the SARS-CoV-2 variants and to elucidate the factors protecting some infected individuals from developing clinical COVID-19.},

keywords = {Adolescent, Adult, Antibodies, Burkina Faso / epidemiology, Child, COVID-19* / epidemiology, doi:10.1111/irv.13216, Humans, Isidore Tiandiogo Traor\'{e}, MEDLINE, Middle Aged, National Center for Biotechnology Information, National Institutes of Health, National Library of Medicine, NCBI, NIH, NLM, PMC10655778, pmid:38019697, PubMed Abstract, Samiratou Ou\'{e}draogo, SARS-CoV-2*, Seroepidemiologic Studies, Surveys and Questionnaires, Tienhan Sandrine Dabakuyo-Yonli, Viral},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Strong off-target antibody reactivity to malarial antigens induced by RTS,S/AS01E vaccination is associated with protection.},

author = {D\'{i}dac Maci\`{a} and Joseph J. Campo and Gemma Moncunill and Chenjerai Jairoce and Augusto J. Nhabomba and Maximilian Mpina and Hermann Sorgho and David Dosoo and Ousmane Traore and Kwadwo Asamoah Kusi and Nana Aba Williams and Amit Oberai and Arlo Randall and H\`{e}ctor Sanz and Clarissa Valim and Kwaku Poku Asante and Seth Owusu-Agyei and Halidou Tinto and Selidji Todagbe Agnandji and Simon Kariuki and Ben Gyan and Claudia Daubenberger and Benjamin Mordm\"{u}ller and Paula Petrone and Carlota Doba\~{n}o},

doi = {10.1172/jci.insight.158030},

issn = {2379-3708},

year  = {2022},

date = {2022-05-01},

urldate = {2022-05-01},

journal = {JCI insight},

volume = {7},

issue = {10},

abstract = {The RTS,S/AS01E vaccine targets the circumsporozoite protein (CSP) of the Plasmodium falciparum (P. falciparum) parasite. Protein microarrays were used to measure levels of IgG against 1000 P. falciparum antigens in 2138 infants (age 6-12 weeks) and children (age 5-17 months) from 6 African sites of the phase III trial, sampled before and at 4 longitudinal visits after vaccination. One month postvaccination, IgG responses to 17% of all probed antigens showed differences between RTS,S/AS01E and comparator vaccination groups, whereas no prevaccination differences were found. A small subset of antigens presented IgG levels reaching 4- to 8-fold increases in the RTS,S/AS01E group, comparable in magnitude to anti-CSP IgG levels (~11-fold increase). They were strongly cross-correlated and correlated with anti-CSP levels, waning similarly over time and reincreasing with the booster dose. Such an intriguing phenomenon may be due to cross-reactivity of anti-CSP antibodies with these antigens. RTS,S/AS01E vaccinees with strong off-target IgG responses had an estimated lower clinical malaria incidence after adjusting for age group, site, and postvaccination anti-CSP levels. RTS,S/AS01E-induced IgG may bind strongly not only to CSP, but also to unrelated malaria antigens, and this seems to either confer, or at least be a marker of, increased protection from clinical malaria.},

keywords = {*Adaptive immunity, *Antigen, *Epidemiology, *Immunology, *Infectious disease, *Malaria, *Malaria Vaccines, *Malaria/prevention \& control, Antibodies, Antigens, Child, Falciparum/prevention \& control, Humans, Immunoglobulin G, Infant, Protozoan, Vaccination},

pubstate = {published},

tppubtype = {article}

}