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Bell, Griffin J.; Gyaase, Stephaney; Goel, Varun; Adu, Bright; Mensah, Benedicta A.; Essone, Paulin; Dosoo, David; Osei, Musah; Niare, Karamoko; & Wiru, Kenneth, et al. (Preprint). Malaria Transmission Intensity and Parasitemia during the Three-Dose RTS,S/AS01 Vaccination Series do not Reduce Magnitude of Antibody Response nor Efficacy Against the First Case of Malaria. Research Square. PMCID: PMC10246269


Background: RTS,S/AS01 has been recommended by WHO for widespread implementation in medium to high malaria transmission settings. Previous analyses have noted lower vaccine efficacies in higher transmission settings, possibly due to the more rapid development of naturally acquired immunity in the control group.
Methods: To investigate a reduced immune response to vaccination as a potential mechanism behind lower efficacy in high transmission areas, we examine initial vaccine antibody (anti-CSP IgG) response and vaccine efficacy against the first case of malaria to exclude the delayed malaria effect using data from three study areas (Kintampo, Ghana; Lilongwe, Malawi; Lambaréné, Gabon) from the 2009-2014 phase III trial (NCT00866619). Our key exposures are parasitemia during the vaccination series and malaria transmission intensity. We calculate vaccine efficacy (one minus hazard ratio) using a cox-proportional hazards model and allowing for the time-varying effect of RTS,S/AS01.
Results: We find that antibody responses to the primary three-dose vaccination series were higher in Ghana than in Malawi and Gabon, but that neither antibody levels nor vaccine efficacy against the first case of malaria varied by transmission intensity or parasitemia during the primary vaccination series.
Conclusions: We find that vaccine efficacy is unrelated to infections during vaccination. Contributing to a conflicting literature, our results suggest that vaccine efficacy is also unrelated to infections before vaccination, meaning that delayed malaria is likely the main reason for lower efficacy in high transmission settings, not reduced immune responses. This may be reassuring for implementation in high transmission settings, though further studies are needed.


Reference Type

Journal Article

Year Published


Journal Title

Research Square


Bell, Griffin J.
Gyaase, Stephaney
Goel, Varun
Adu, Bright
Mensah, Benedicta A.
Essone, Paulin
Dosoo, David
Osei, Musah
Niare, Karamoko
Wiru, Kenneth
Brandt, Katerina
Emch, Michael E.
Ghansah, Anita
Asante, Kwaku P.
Mvalo, Tisungane
Agnandji, Selidji T.
Juliano, Jonathan J.
Bailey, Jeffrey A.

Article Type





Emch - 0000-0003-2642-965X
Bell, G - 0000-0003-4367-135X
Goel - 0000-0002-2933-427X
Brandt - 0000-0003-2529-7720