Dr. Mike Emch won a huge grant, “Impacts of Environment, Host Genetics and Antigen Diversity on Malaria Vaccine Efficacy,” funded by the National Institute of Allergies and Infectious Disease, National Institutes of Health (NIH),1R01-AI137410-01, $3,632,091, 2018-22.

This is an NIH RO1 project that is a collaboration between Michael Emch (UNC-PI), Jon Juliano (UNC Medicine-CoPI), Michael Hudgens (UNC Biostatistics- CoI), and Jeff Bailey (UMass- PI). Malaria remains a major global public health problem but global malaria elimination has little chance of success in the absence of an effective vaccine. This project investigates the interactions between the malaria vaccine called RTS,S and environmental factors, host genetics, parasite genetic diversity, and other malaria control measures. The vaccine has shown only moderate efficacy in a completed Phase III trial but in 2017 it was licensed for use because it has the potential to make a large impact given the magnitude of malaria burden. The vaccine does not work equally well in different populations; this variability may be due to parasite, environmental, or host factors. Furthermore, any malaria vaccine will not be used in isolation, but rather as part of an integrated program leveraging other control measures such as bed nets and insecticides. Therefore, understanding the combinations of factors, which modulate the effectiveness of a malaria vaccine is essential to guide appropriate vaccine use and formulating next-generation vaccines.

This study is designed to improve our understanding of how RTS,S works by evaluating key ecological, host, and parasite factors which likely impact effectiveness. The approaches that we will use enhance our understanding of the effectiveness of RTS,S and can also be leveraged to improve the efficacy of future malaria vaccines. We will investigate ecological and behavioral factors that may influence vaccine efficacy across three RTS,S trial sites in Ghana, Gabon, and Malawi. These data, in conjunction with Phase III trial data, geographic information system (GIS) and satellite data, and a concurrent malaria transmission intensity study, will allow us to discern the impacts of individual and neighborhood factors on vaccine effectiveness in an “ecological” analysis of the trial.

The second goal is to understand how well the vaccine works against different genetic strains of the malaria parasite.  Recent evidence has shown strain selection by the vaccine, with a higher level of vaccine efficacy against vaccine type CS strains, however, the longevity of strain specific immunity is not known. If immunity to the vaccine type CS strains is longer-lasting than to non-vaccine type strains, this has important implications for vaccine design and suggests the need for a polyvalent vaccine (i.e., one that protects against multiple strains). The third goal is to measure the impacts of human genetics on RTS,S malaria vaccine efficacy. The fourth goal is to provide an integrative analysis of the key factors identified in the first three goals of the project to assess their impact on vaccine efficacy in multivariate analysis. This study will be the most comprehensive evaluation to date of factors, including host, parasite and environmental, that affect RTS,S effectiveness. This information will be critical for informing current large-scale rollouts of RTS,S and future malaria vaccine trials.

 

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