The Anti-Circumsporozoite Antibody Response of Children to Seasonal Vaccination With the RTS,S/AS01E Malaria Vaccine

Issaka Sagara, Issaka Zongo, Matthew Cairns, Rakiswendé Serge Yerbanga, Almahamoudou Mahamar, Frédéric Nikièma, Amadou Tapily, Frédéric Sompougdou, Modibo Diarra, Charles Zoungrana, Djibrilla Issiaka, Alassane Haro, Koualy Sanogo, Abdoul Aziz Sienou, Mahamadou Kaya, Seydou Traore, Ismaila Thera, Kalifa Diarra, Amagana Dolo, Irene Kuepfer, Paul Snell, Paul Milligan, Christian Ockenhouse, Opokua Ofori-Anyinam, Halidou Tinto, Abdoulaye Djimde, Jean Bosco Ouedraogo, Alassane Dicko, Daniel Chandramohan, Brian Greenwood, Issaka Sagara, Issaka Zongo, Matthew Cairns, Rakiswendé Serge Yerbanga, Almahamoudou Mahamar, Frédéric Nikièma, Amadou Tapily, Frédéric Sompougdou, Modibo Diarra, Charles Zoungrana, Djibrilla Issiaka, Alassane Haro, Koualy Sanogo, Abdoul Aziz Sienou, Mahamadou Kaya, Seydou Traore, Ismaila Thera, Kalifa Diarra, Amagana Dolo, Irene Kuepfer, Paul Snell, Paul Milligan, Christian Ockenhouse, Opokua Ofori-Anyinam, Halidou Tinto, Abdoulaye Djimde, Jean Bosco Ouedraogo, Alassane Dicko, Daniel Chandramohan, Brian Greenwood

Abstract

Background: A trial in African children showed that combining seasonal vaccination with the RTS,S/AS01E vaccine with seasonal malaria chemoprevention reduced the incidence of uncomplicated and severe malaria compared with either intervention given alone. Here, we report on the anti-circumsporozoite antibody response to seasonal RTS,S/AS01E vaccination in children in this trial.

Methods: Sera from a randomly selected subset of children collected before and 1 month after 3 priming doses of RTS,S/AS01E and before and 1 month after 2 seasonal booster doses were tested for anti-circumsporozoite antibodies using enzyme-linked immunosorbent assay. The association between post-vaccination antibody titer and incidence of malaria was explored.

Results: A strong anti-circumsporozoite antibody response to 3 priming doses of RTS,S/AS01E was seen (geometric mean titer, 368.9 enzyme-linked immunosorbent assay units/mL), but titers fell prior to the first booster dose. A strong antibody response to an annual, pre-malaria transmission season booster dose was observed, but this was lower than after the primary vaccination series and lower after the second than after the first booster dose (ratio of geometric mean rise, 0.66; 95% confidence interval [CI], .57-.77). Children whose antibody response was in the upper tercile post-vaccination had a lower incidence of malaria during the following year than children in the lowest tercile (hazard ratio, 0.43; 95% CI, .28-.66).

Conclusions: Seasonal vaccination with RTS,S/AS01E induced a strong booster antibody response that was lower after the second than after the first booster dose. The diminished antibody response to the second booster dose was not associated with diminished efficacy.

Clinical trials registration: NCT03143218.

Keywords: Burkina Faso; Mali; RTS; S/AS01E vaccine; anti-circumsporozoite antibody; seasonal vaccination.

Conflict of interest statement

Potential conflicts of interest. O. O.-A. is an employee of the GSK group of companies and has restricted shares in the GSK group of companies. A. D. reports a research grant from Grand Challenges Canada to test safety and efficacy of the PfSPZ vaccine for pregnant women and unborn children and a research contract with Oxford University to conduct a phase 3 randomized, controlled multicenter trial to evaluate the efficacy of the R21/Matrix-M vaccine in African children against clinical malaria outside of the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Schematic showing the interventions given to children in each of the 3 trial groups and their timing in relation to the malaria transmission seasons in 2017, 2018, and 2019. The timing of the collection of serological samples and of the cross-sectional surveys when samples were collected for malaria microscopy are also shown. Abbreviation: SMC, seasonal malaria chemoprevention.
Figure 2.
Figure 2.
Anti-CSP antibody titers in individual children pre- and post-priming vaccination (2017) and pre and post first (2018) and second (2019) booster seasonal vaccination doses are shown by country. Results from children in the RTS,S/AS01E alone group are shown in red, those from children in the combined group are shown in blue. Children who developed a clinical episode of malaria in the year after priming or booster vaccination are indicated in black. Abbreviations: CSP, circumsporozoite; EU, enzyme-linked immunosorbent assay unit.
Figure 3.
Figure 3.
Reverse cumulative plots of antibody titer by study year, country, and study arm are shown. The top row shows post-vaccination titers in 2017, the middle row shows post-vaccination titers in 2018, and the bottom row shows post-vaccination titers in 2019. The right-hand set of panels shows titers by study country—Burkina Faso (solid red line), Mali (dashed blue line). The left-hand set of panels shows titers by study group—RTS,S/AS01E alone group (solid red line), combined intervention group (dashed green line). Abbreviations: CSP, circumsporozoite; EU, enzyme-linked immunosorbent assay unit.

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