Heterogeneity in malaria exposure and vaccine response: implications for the interpretation of vaccine efficacy trials
Open Access
- 23 March 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in Malaria Journal
- Vol. 9 (1), 82
- https://doi.org/10.1186/1475-2875-9-82
Abstract
Phase III trials of the malaria vaccine, RTS, S, are now underway across multiple sites of varying transmission intensity in Africa. Heterogeneity in exposure, vaccine response and waning of efficacy may bias estimates of vaccine efficacy. Theoretical arguments are used to identify the expected effects of a) heterogeneity in exposure to infectious bites; b) heterogeneity in individual's response to the vaccine; and c) waning efficacy on measures of vaccine efficacy from clinical trials for an infection-blocking vaccine. Heterogeneity in exposure and vaccine response leads to a smaller proportion of trial participants becoming infected than one would expect in a homogeneous setting. This causes estimates of vaccine efficacy from clinical trials to be underestimated if transmission heterogeneity is ignored, and overestimated if heterogeneity in vaccine response is ignored. Waning of vaccine efficacy can bias estimates of vaccine efficacy in both directions. Failure to account for heterogeneities in exposure and response, and waning of efficacy in clinical trials can lead to biased estimates of malaria vaccine efficacy. Appropriate methods to reduce these biases need to be used to ensure accurate interpretation and comparability between trial sites of results from the upcoming Phase III clinical trials of RTS, S.Keywords
This publication has 34 references indexed in Scilit:
- What you see is not what you get: implications of the brevity of antibody responses to malaria antigens and transmission heterogeneity in longitudinal studies of malaria immunityMalaria Journal, 2009
- Long‐Term Safety and Efficacy of the RTS,S/AS02A Malaria Vaccine in Mozambican ChildrenThe Journal of Infectious Diseases, 2009
- Analysis of Immunity to Febrile Malaria in Children That Distinguishes Immunity from Lack of ExposureInfection and Immunity, 2009
- Safety and Immunogenicity of RTS,S/AS02D Malaria Vaccine in InfantsNew England Journal of Medicine, 2008
- Efficacy of RTS,S/AS01E Vaccine against Malaria in Children 5 to 17 Months of AgeNew England Journal of Medicine, 2008
- Effect of a fall in malaria transmission on morbidity and mortality in Kilifi, KenyaThe Lancet, 2008
- Changes in malaria indices between 1999 and 2007 in The Gambia: a retrospective analysisThe Lancet, 2008
- What Should Vaccine Developers Ask? Simulation of the Effectiveness of Malaria VaccinesPLOS ONE, 2008
- Estimation of vaccine efficacy in a repeated measures study under heterogeneity of exposure or susceptibility to infectionPhilosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences, 2008
- The global distribution of clinical episodes of Plasmodium falciparum malariaNature, 2005