Estimates of infected hepatocyte numbers responsible for subsequent blood-stage parasite load and growth in vaccinees proved to be a good predictor of time to slide positive parasitaemia across all challenged subjects. This study was designed to assess a possible liver stage effect of vaccination, selleck but if a significant blood stage effect had been anticipated then a blood stage challenge
protocol [29] may have been preferable. There is an increasing consensus in the malaria vaccine development field that multiple antigens will be required in a vaccine to achieve high levels of efficacy in field trials. Heterologous prime-boost immunisation has been one of the very few approaches to successfully induce sterile efficacy in any human vaccinees and this study has assessed a polyprotein
approach to broadening the immunogenicity of the induced T cell responses. Our results suggest that there may be limits to the insert size that will be readily immunogenic in humans, at least using standard vaccinia promoters. Hence other vector design strategies, such as the use of multiple promoters and insertion sites [30], or mixtures of single vaccines may be more suitable for exploiting the great capacity of poxviruses to express foreign antigens. This study was principally funded by the European Malaria Vaccine Initiative (EMVI) now European Vaccine Initiative (EVI). The authors would PLX4032 clinical trial like to thank Odile Leroy and Egeruan Imoukhuede for advice and support. Additional support from the Wellcome Trust and the NIHR Oxford Biomedical Research Centre is gratefully acknowledged. SG is a Jenner Institute Investigator Tolmetin and AVSH is a Wellcome Trust Principal Research Fellow. “
“Complex
antigenic polymorphisms present a significant challenge for design of a vaccine against the malaria parasite Plasmodium falciparum. Although partial protection offered by the current leading malaria vaccine candidate RTS,S appears not to be compromised by limited polymorphism in the pre-erythrocytic circumsporozoite protein [1], the problem of polymorphism is likely to be more important for vaccines based on blood-stage parasite proteins that are targets of naturally acquired immunity [2] and [3]. The extracellular merozoite that invades erythrocytes is an important target of immunity [4], and a leading vaccine candidate is the most abundant surface component, merozoite surface protein 1 (MSP1) which is expressed as a large ∼200 kDa precursor that needs to be proteolytically processed to allow merozoite maturation [5]. Antibodies to several parts of the protein can inhibit this processing [6], but most research has focused on the C-terminal region, particularly the 19 kDa C-terminal fragment MSP1-19 [7], [8], [9] and [10].
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