title: Duration of vaccine efficacy against malaria: 5th year of follow-up in children vaccinated with RTS,S/AS02 in Mozambique.
abstract: A primary concern for the RTS,S malaria vaccine candidate is duration of protection. The ongoing Phase III trial reported evidence of waning efficacy within the first year following vaccination. Multiple Phase IIb trials demonstrated early waning of efficacy. The longest duration of protection for RTS,S recorded to date was in a trial of a cohort of 1605 Mozambican children age 1-4 yr at the time of immunization (C1), which showed an overall efficacy against clinical malaria of 30.5% over 43 subsequent months of surveillance. A significant reduction in parasite prevalence in RTS,S vaccinees indicated that the vaccine continued to protect at the end of this period. Although follow-up for recording incident cases of clinical malaria was stopped at 45 months, we were interested in evidence of further durability of protection, and revisited the cohort at 63 months, recording the secondary trial endpoint, prevalence of asexual Plasmodium falciparum parasitemia, in the RTS,S and comparator vaccine groups as a proxy for efficacy. As a comparator, we also visited the contemporaneous cohort of 417 children (C2), which showed waning efficacy after 6 months of follow-up. We also assessed anti-circumsporozoite antibody titers. These results were compared with those of other Phase IIb trials. Prevalence of parasitemia was not significantly lower in the RTS,S/AS02 group compared to comparator groups in C1 (57 [119%] Vs 62 [128%]; p=0.696) or C2 (30 [226%] Vs 35 [276%]; p=0.391), despite elevated antibody titers, suggesting that protection did not extend to 5 years after vaccination. This is in contrast to the earlier assessment of parasitemia in C1, where a 34% lower prevalence of parasitemia was observed in the RTS,S/AS02 group at month 45. Comparison with other Phase II trials highlights a complex relationship between efficacy, age and transmission intensity. RTS,S/AS02 provided partial protection from clinical malaria for at least 3.5 years in C1. Duration of protection may depend on environmental circumstances, such as changing malaria transmission, and special attention should be given in the Phase III trial to identifying factors that modify longevity of protection.
authors.affiliation: Barcelona Centre for International Health Research CRESIB, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain; Centro de Investigaçao em Saúde de Manhiça (CISM), Manhiça, Mozambique. Electronic address: joe.campo@cresib.cat.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Campo
authors.affiliation: Centro de Investigaçao em Saúde de Manhiça (CISM), Manhiça, Mozambique; Faculdade de Medicina, Universidade Eduardo Mondlane, Maputo, Mozambique.
authors.forename: Jahit
authors.initials: J
authors.lastname: Sacarlal
authors.affiliation: Barcelona Centre for International Health Research CRESIB, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain; Centro de Investigaçao em Saúde de Manhiça (CISM), Manhiça, Mozambique.
authors.forename: John J
authors.initials: JJ
authors.lastname: Aponte
authors.affiliation: Barcelona Centre for International Health Research CRESIB, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain; Instituto Nacional de Saúde, Ministério de Saúde, Maputo, Mozambique.
authors.forename: Pedro
authors.initials: P
authors.lastname: Aide
authors.affiliation: Centro de Investigaçao em Saúde de Manhiça (CISM), Manhiça, Mozambique.
authors.forename: Augusto J
authors.initials: AJ
authors.lastname: Nhabomba
authors.affiliation: Barcelona Centre for International Health Research CRESIB, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain; Centro de Investigaçao em Saúde de Manhiça (CISM), Manhiça, Mozambique.
authors.forename: Carlota
authors.initials: C
authors.lastname: Dobaño
authors.affiliation: Barcelona Centre for International Health Research CRESIB, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain; Centro de Investigaçao em Saúde de Manhiça (CISM), Manhiça, Mozambique.
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Alonso
mesh_terms: D000913:Antibodies, Protozoan / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D003430:Cross-Sectional Studies; D005500:Follow-Up Studies; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D017780:Malaria Vaccines / Q000276:immunology / Q000627:therapeutic use*; D016778:Malaria, Falciparum / Q000517:prevention & control*; D009073:Mozambique; D018512:Parasitemia / Q000517:prevention & control*; D010963:Plasmodium falciparum; D016032:Randomized Controlled Trials as Topic
chemical_list: D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D017780:Malaria Vaccines; C533817:RTS,S-AS02D vaccine
keywords: Immunogenicity; Plasmodium falciparum; Prevalence; RTS,S; Vaccine