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[Preprint]. 2023 May 25:rs.3.rs-2960373.
doi: 10.21203/rs.3.rs-2960373/v1.

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

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

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

Griffin J Bell et al. Res Sq. .

Update in

Abstract

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.

Keywords: Africa; GIS; delayed malaria; geographic information system; immunology; rebound malaria; vaccine.

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Conflict of interest statement

Conflicts of Interest The authors declare no conflicts of interest. GlaxoSmithKline Biologicals SA was provided the opportunity to review a preliminary version of this manuscript for factual accuracy, but the authors are solely responsible for final content and interpretation.

Figures

Figure 1
Figure 1
Anti-CSP Antibody Response by Transmission Intensity, All Study Areas and Study Area Adjusted (A: Pre-Vaccination, B: One Month Post-Vaccination) (A) Children have a very low anti-circumsporozoite protein (CSP) antibody response on the day of the first vaccine dose. (B) One month after vaccination, children in higher transmission areas have higher antibody responses to RTS,S/AS01 vaccination. This positive relationship disappears when adjusting for study area. Antibody responses were elevated in Ghana, the highest transmission study area.
Figure 2
Figure 2
Anti-CSP Antibody Response (One Month Post-Vaccination) in RTS,S/AS01 Group
Figure 3
Figure 3
Efficacy Against the First Case of Malaria Over Time, Transmission Intensity, and Cases During Vaccination
See this image and copyright information in PMC

References

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