Identification of two new protective pre-erythrocytic malaria vaccine antigen candidates

<p>Abstract</p> <p>Background</p> <p>Despite years of effort, a licensed malaria vaccine is not yet available. One of the obstacles facing the development of a malaria vaccine is the extensive heterogeneity of many of the current malaria vaccine antigens. To counteract this antigenic diversity, an effective malaria vaccine may need to elicit an immune response against multiple malaria antigens, thereby limiting the negative impact of variability in any one antigen. Since most of the malaria vaccine antigens that have been evaluated in people have not elicited a protective immune response, there is a need to identify additional protective antigens. In this study, the efficacy of three pre-erythrocytic stage malaria antigens was evaluated in a <it>Plasmodium yoelii</it>/mouse protection model.</p> <p>Methods</p> <p>Mice were immunized with plasmid DNA and vaccinia virus vectors that expressed one, two or all three <it>P. yoelii </it>vaccine antigens. The immunized mice were challenged with 300 <it>P. yoelii </it>sporozoites and evaluated for subsequent infection.</p> <p>Results</p> <p>Vaccines that expressed any one of the three antigens did not protect a high percentage of mice against a <it>P. yoelii </it>challenge. However, vaccines that expressed all three antigens protected a higher percentage of mice than a vaccine that expressed PyCSP, the most efficacious malaria vaccine antigen. Dissection of the multi-antigen vaccine indicated that protection was primarily associated with two of the three <it>P. yoelii </it>antigens. The protection elicited by a vaccine expressing these two antigens exceeded the sum of the protection elicited by the single antigen vaccines, suggesting a potential synergistic interaction.</p> <p>Conclusions</p> <p>This work identifies two promising malaria vaccine antigen candidates and suggests that a multi-antigen vaccine may be more efficacious than a single antigen vaccine.</p

First report on dung beetles in intra-Amazonian savannahs in Roraima, Brazil

This is the first study to address the dung beetle (Coleoptera: Scarabaeidae: Scarabaeinae) diversity in intra-Amazonian savannahs in the state of Roraima, Brazil. Our aim was to survey the dung beetle fauna associated with these savannahs (regionally called 'lavrado'), since little is known about the dung beetles from this environment. We conducted three field samples using pitfall traps baited with human dung in savannah areas near the city of Boa Vista during the rainy seasons of 1996, 1997, and 2008. We collected 383 individuals from ten species, wherein six have no previous record in intra-Amazonian savannahs. The most abundant species were Ontherus appendiculatus (Mannerheim, 1829), Canthidium aff. humerale (Germar, 1813), Dichotomius nisus (Olivier, 1789), and Pseudocanthon aff. xanthurus (Blanchard, 1846). We believe that knowing the dung beetles diversity associated with the intra-Amazonian savannahs is ideal for understanding the occurrence and distribution of these organisms in a highly threatened environment, it thus being the first step towards conservation strategy development

Adenovirus-5-Vectored P. falciparum Vaccine Expressing CSP and AMA1. Part B: Safety, Immunogenicity and Protective Efficacy of the CSP Component

Background: A protective malaria vaccine will likely need to elicit both cell-mediated and antibody responses. As adenovirus vaccine vectors induce both these responses in humans, a Phase 1/2a clinical trial was conducted to evaluate the efficacy of an adenovirus serotype 5-vectored malaria vaccine against sporozoite challenge.\ud \ud Methodology/Principal Findings: NMRC-MV-Ad-PfC is an adenovirus vector encoding the Plasmodium falciparum 3D7 circumsporozoite protein (CSP). It is one component of a two-component vaccine NMRC-M3V-Ad-PfCA consisting of one adenovector encoding CSP and one encoding apical membrane antigen-1 (AMA1) that was evaluated for safety and immunogenicity in an earlier study (see companion paper, Sedegah et al). Fourteen Ad5 seropositive or negative adults received two doses of NMRC-MV-Ad-PfC sixteen weeks apart, at 1x1010 particle units per dose. The vaccine was safe and well tolerated. All volunteers developed positive ELISpot responses by 28 days after the first immunization (geometric mean 272 spot forming cells/million[sfc/m]) that declined during the following 16 weeks and increased after the second dose to levels that in most cases were less than the initial peak (geometric mean 119 sfc/m). CD8+ predominated over CD4+ responses, as in the first clinical trial. Antibody responses were poor and like ELISpot responses increased after the second immunization but did not exceed the initial peak. Pre-existing neutralizing antibodies (NAb) to Ad5 did not affect the immunogenicity of the first dose, but the fold increase in NAb induced by the first dose was significantly associated with poorer antibody responses after the second dose, while ELISpot responses remained unaffected. When challenged by the bite of P. falciparum-infected mosquitoes, two of 11 volunteers showed a delay in the time to patency compared to infectivity controls, but no volunteers were sterilely protected.\ud \ud Significance: The NMRC-MV-Ad-PfC vaccine expressing CSP was safe and well tolerated given as two doses, but did not provide sterile protection