Seven-year kinetics of RTS, S/AS01-induced anti-CSP antibodies in young Kenyan children

Robert M Mugo,Jennifer N Musyoki,Edward Otieno,Philip Bejon,Faiz M Shee,Juliana Wambua,Jedidah Mwacharo,Kennedy Mwai,Francis M Ndungu

doi:10.1186/s12936-021-03961-2

Abstract

BackgroundRTS,S/AS01, the leading malaria vaccine has been recommended by the WHO for widespread immunization of children at risk. RTS,S/AS01-induced anti-CSP IgG antibodies are associated with the vaccine efficacy. Here, the long-term kinetics of RTS,S/AS01-induced antibodies was investigated.Methods150 participants were randomly selected from the 447 children who participated in the RTS,S/AS01 phase IIb clinical trial in 2007 from Kilifi-Kenya. Cumulatively, the retrospective follow-up period was 93 months with annual plasma samples collection. The levels of anti-CSP IgM, total IgG, IgG1, IgG2, IgG3, and IgG4 antibodies were then determined using an enzyme-linked immunosorbent assay.ResultsRTS,S/AS01 induced high levels of anti-CSP IgG antibodies which exhibited a rapid waning over 6.5 months post-vaccination, followed by a slower decay over the subsequent years. RTS,S/AS01-induced anti-CSP IgG antibodies remained elevated above the control group levels throughout the 7 years follow-up period. The anti-CSP IgG antibodies were mostly IgG1, IgG3, IgG2, and to a lesser extent IgG4. IgG2 predominated in later timepoints. RTS,S/AS01 also induced high levels of anti-CSP IgM antibodies which increased above the control group levels by month 3. The controls exhibited increasing levels of the anti-CSP IgM antibodies which caught up with the RTS,S/AS01 vaccinees levels by month 21. In contrast, there were no measurable anti-CSP IgG antibodies among the controls.ConclusionRTS,S/AS01-induced anti-CSP IgG antibodies kinetics are consistent with long-lived but waning vaccine efficacy. Natural exposure induces anti-CSP IgM antibodies in children, which increases with age, but does not induce substantial levels of anti-CSP IgG antibodies.

Highlights

RTS,S/AS01, the leading malaria vaccine has been recommended by the World Health Organization (WHO) for widespread immunization of children at risk
RTS,S/AS01 is a recombinant Plasmodium falciparum vaccine based on the circumsporozoite protein (CSP) which is the major protein on the surface of the sporozoites
Kinetics of RTS,S/AS01‐induced anti‐CSP Immunoglobulin G (IgG), and Immunoglobulin M (IgM) responses Plasma samples collected during the 7 years follow-up period were tested for the IgG and IgM Abs levels in both the vaccine and control groups against the immunodominant central repeat region of P. falciparum CSP (NANP)9

Summary

Introduction

RTS,S/AS01, the leading malaria vaccine has been recommended by the WHO for widespread immunization of children at risk. RTS,S/AS01-induced anti-CSP IgG antibodies are associated with the vaccine efficacy. Wide-scale malaria control efforts have been implemented in malaria-endemic countries, including indoor residual spraying of insecticide, sleeping under long-lasting insecticide-treated bed nets, RTS,S/AS01 malaria vaccine has been tested in a phase III clinical trial and shown to provide partial protection. RTS,S/AS01 is a recombinant Plasmodium falciparum vaccine based on the circumsporozoite protein (CSP) which is the major protein on the surface of the sporozoites. The vaccine construct has 19 copies of the central repeat region (NANP) which contains known immunodominant B-cell epitopes and the C-terminal, which contains T-cell epitopes fused to hepatitis B surface antigen (HBsAg). The two regions are simultaneously co-expressed with un-fused HBsAg in yeast cells. Co-expression with HBsAg enhances the vaccine immunogenicity and stability [4]

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