A seven-year study on the effect of the pre-erythrocytic malaria vaccine candidate RTS,S/AS01E on blood stage immunity in young Kenyan children [version 1; peer review: 1 approved, 2 approved with reservations]
Background: RTS,S/AS01 E, the most advanced malaria vaccine confers partial immunity. The vaccine-induced pre-erythrocytic immunity reduces exposure to blood-stage parasites, delaying acquisition of antibodies to blood-stage antigens. However, the duration of this effect is unknown. Methods: We mea...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wellcome
2019-03-01
|
| Series: | Wellcome Open Research |
| Online Access: | https://wellcomeopenresearch.org/articles/4-42/v1 |
| _version_ | 1828389571379855360 |
|---|---|
| author | Francis M. Ndungu Jedida Mwacharo Juliana Wambua Patricia Njuguna Kevin Marsh Chris Drakeley Philip Bejon |
| author_facet | Francis M. Ndungu Jedida Mwacharo Juliana Wambua Patricia Njuguna Kevin Marsh Chris Drakeley Philip Bejon |
| author_sort | Francis M. Ndungu |
| collection | DOAJ |
| description | Background: RTS,S/AS01 E, the most advanced malaria vaccine confers partial immunity. The vaccine-induced pre-erythrocytic immunity reduces exposure to blood-stage parasites, delaying acquisition of antibodies to blood-stage antigens. However, the duration of this effect is unknown. Methods: We measured, by enzyme-linked immunosorbent assay, IgG-antibodies to 4 Plasmodium falciparum blood-stage antigens (AMA1, MSP142, EBA175, and MSP3) on 314 children randomized to receive RTS,S/AS01 E or Rabies vaccine at 5 – 17 months of age in a phase 2b trial in Kenya, and thereafter participated in a 7-year study of the duration of vaccine immunity. Results: Antibody levels to MSP142, AMA1 and EBA175 were slightly lower among the RTS,S/AS01 E recipients, relative to the Rabies-control vaccinees, during the first 48 months of surveillance. Irrespective of vaccine arm, antibody levels to merozoite antigens were positively associated with the risk for malaria. However, this was only apparent at high levels for EBA175 and AMA1 and was not evident after adjusting for heterogeneity in malaria-exposure. Among children with asymptomatic parasitaemia, antibody levels were associated with reduced clinical malaria. Conclusions: The reduction in levels of antibodies to blood-stage antigens induced by vaccination with RTS,S/AS01 E can last for several years. In absence of asymptomatic infection, anti-merozoite antibody levels were unreliable correlates of clinical immunity. |
| first_indexed | 2024-12-10T06:31:25Z |
| format | Article |
| id | doaj.art-44055e6b44734049b940e671065276c3 |
| institution | Directory Open Access Journal |
| issn | 2398-502X |
| language | English |
| last_indexed | 2024-12-10T06:31:25Z |
| publishDate | 2019-03-01 |
| publisher | Wellcome |
| record_format | Article |
| series | Wellcome Open Research |
| spelling | doaj.art-44055e6b44734049b940e671065276c32022-12-22T01:59:03ZengWellcomeWellcome Open Research2398-502X2019-03-01410.12688/wellcomeopenres.15002.116366A seven-year study on the effect of the pre-erythrocytic malaria vaccine candidate RTS,S/AS01E on blood stage immunity in young Kenyan children [version 1; peer review: 1 approved, 2 approved with reservations]Francis M. Ndungu0Jedida Mwacharo1Juliana Wambua2Patricia Njuguna3Kevin Marsh4Chris Drakeley5Philip Bejon6Department of Biosciences, KEMRI/Wellcome Trust Research Programme, Kilifi, 80108, KenyaDepartment of Biosciences, KEMRI/Wellcome Trust Research Programme, Kilifi, 80108, KenyaDepartment of Biosciences, KEMRI/Wellcome Trust Research Programme, Kilifi, 80108, KenyaDepartment of Biosciences, KEMRI/Wellcome Trust Research Programme, Kilifi, 80108, KenyaDepartment of Biosciences, KEMRI/Wellcome Trust Research Programme, Kilifi, 80108, KenyaInfection & Immunity Department, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UKInfection & Immunity Department, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UKBackground: RTS,S/AS01 E, the most advanced malaria vaccine confers partial immunity. The vaccine-induced pre-erythrocytic immunity reduces exposure to blood-stage parasites, delaying acquisition of antibodies to blood-stage antigens. However, the duration of this effect is unknown. Methods: We measured, by enzyme-linked immunosorbent assay, IgG-antibodies to 4 Plasmodium falciparum blood-stage antigens (AMA1, MSP142, EBA175, and MSP3) on 314 children randomized to receive RTS,S/AS01 E or Rabies vaccine at 5 – 17 months of age in a phase 2b trial in Kenya, and thereafter participated in a 7-year study of the duration of vaccine immunity. Results: Antibody levels to MSP142, AMA1 and EBA175 were slightly lower among the RTS,S/AS01 E recipients, relative to the Rabies-control vaccinees, during the first 48 months of surveillance. Irrespective of vaccine arm, antibody levels to merozoite antigens were positively associated with the risk for malaria. However, this was only apparent at high levels for EBA175 and AMA1 and was not evident after adjusting for heterogeneity in malaria-exposure. Among children with asymptomatic parasitaemia, antibody levels were associated with reduced clinical malaria. Conclusions: The reduction in levels of antibodies to blood-stage antigens induced by vaccination with RTS,S/AS01 E can last for several years. In absence of asymptomatic infection, anti-merozoite antibody levels were unreliable correlates of clinical immunity.https://wellcomeopenresearch.org/articles/4-42/v1 |
| spellingShingle | Francis M. Ndungu Jedida Mwacharo Juliana Wambua Patricia Njuguna Kevin Marsh Chris Drakeley Philip Bejon A seven-year study on the effect of the pre-erythrocytic malaria vaccine candidate RTS,S/AS01E on blood stage immunity in young Kenyan children [version 1; peer review: 1 approved, 2 approved with reservations] Wellcome Open Research |
| title | A seven-year study on the effect of the pre-erythrocytic malaria vaccine candidate RTS,S/AS01E on blood stage immunity in young Kenyan children [version 1; peer review: 1 approved, 2 approved with reservations] |
| title_full | A seven-year study on the effect of the pre-erythrocytic malaria vaccine candidate RTS,S/AS01E on blood stage immunity in young Kenyan children [version 1; peer review: 1 approved, 2 approved with reservations] |
| title_fullStr | A seven-year study on the effect of the pre-erythrocytic malaria vaccine candidate RTS,S/AS01E on blood stage immunity in young Kenyan children [version 1; peer review: 1 approved, 2 approved with reservations] |
| title_full_unstemmed | A seven-year study on the effect of the pre-erythrocytic malaria vaccine candidate RTS,S/AS01E on blood stage immunity in young Kenyan children [version 1; peer review: 1 approved, 2 approved with reservations] |
| title_short | A seven-year study on the effect of the pre-erythrocytic malaria vaccine candidate RTS,S/AS01E on blood stage immunity in young Kenyan children [version 1; peer review: 1 approved, 2 approved with reservations] |
| title_sort | seven year study on the effect of the pre erythrocytic malaria vaccine candidate rts s as01e on blood stage immunity in young kenyan children version 1 peer review 1 approved 2 approved with reservations |
| url | https://wellcomeopenresearch.org/articles/4-42/v1 |
| work_keys_str_mv | AT francismndungu asevenyearstudyontheeffectofthepreerythrocyticmalariavaccinecandidatertssas01eonbloodstageimmunityinyoungkenyanchildrenversion1peerreview1approved2approvedwithreservations AT jedidamwacharo asevenyearstudyontheeffectofthepreerythrocyticmalariavaccinecandidatertssas01eonbloodstageimmunityinyoungkenyanchildrenversion1peerreview1approved2approvedwithreservations AT julianawambua asevenyearstudyontheeffectofthepreerythrocyticmalariavaccinecandidatertssas01eonbloodstageimmunityinyoungkenyanchildrenversion1peerreview1approved2approvedwithreservations AT patricianjuguna asevenyearstudyontheeffectofthepreerythrocyticmalariavaccinecandidatertssas01eonbloodstageimmunityinyoungkenyanchildrenversion1peerreview1approved2approvedwithreservations AT kevinmarsh asevenyearstudyontheeffectofthepreerythrocyticmalariavaccinecandidatertssas01eonbloodstageimmunityinyoungkenyanchildrenversion1peerreview1approved2approvedwithreservations AT chrisdrakeley asevenyearstudyontheeffectofthepreerythrocyticmalariavaccinecandidatertssas01eonbloodstageimmunityinyoungkenyanchildrenversion1peerreview1approved2approvedwithreservations AT philipbejon asevenyearstudyontheeffectofthepreerythrocyticmalariavaccinecandidatertssas01eonbloodstageimmunityinyoungkenyanchildrenversion1peerreview1approved2approvedwithreservations AT francismndungu sevenyearstudyontheeffectofthepreerythrocyticmalariavaccinecandidatertssas01eonbloodstageimmunityinyoungkenyanchildrenversion1peerreview1approved2approvedwithreservations AT jedidamwacharo sevenyearstudyontheeffectofthepreerythrocyticmalariavaccinecandidatertssas01eonbloodstageimmunityinyoungkenyanchildrenversion1peerreview1approved2approvedwithreservations AT julianawambua sevenyearstudyontheeffectofthepreerythrocyticmalariavaccinecandidatertssas01eonbloodstageimmunityinyoungkenyanchildrenversion1peerreview1approved2approvedwithreservations AT patricianjuguna sevenyearstudyontheeffectofthepreerythrocyticmalariavaccinecandidatertssas01eonbloodstageimmunityinyoungkenyanchildrenversion1peerreview1approved2approvedwithreservations AT kevinmarsh sevenyearstudyontheeffectofthepreerythrocyticmalariavaccinecandidatertssas01eonbloodstageimmunityinyoungkenyanchildrenversion1peerreview1approved2approvedwithreservations AT chrisdrakeley sevenyearstudyontheeffectofthepreerythrocyticmalariavaccinecandidatertssas01eonbloodstageimmunityinyoungkenyanchildrenversion1peerreview1approved2approvedwithreservations AT philipbejon sevenyearstudyontheeffectofthepreerythrocyticmalariavaccinecandidatertssas01eonbloodstageimmunityinyoungkenyanchildrenversion1peerreview1approved2approvedwithreservations |