Plasmodium vivax Pre-Erythrocytic-Stage Antigen Discovery: Exploiting Naturally Acquired Humoral Responses

Abstract. The development of pre-erythrocytic Plasmodium vivax vaccines is hindered by the lack of in vitro culture systems or experimental rodent models. To help bypass these roadblocks, we exploited the fact that naturally exposed Fy- individuals who lack the Duffy blood antigen (Fy) receptor are less likely to develop blood-stage infections; therefore, they preferentially develop immune responses to pre-erythrocytic-stage parasites, whereas Fy+ individuals experience both liver- and blood-stage infections and develop immune responses to both pre-erythrocytic and erythrocytic parasites. We screened 60 endemic sera from P. vivax-exposed Fy+ or Fy- donors against a protein microarray containing 91 P. vivax proteins with P. falciparum orthologs that were up-regulated in sporozoites. Antibodies against 10 P. vivax antigens were identified in sera from P. vivax-exposed individuals but not unexposed controls. This technology has promising implications in the discovery of potential vaccine candidates against P. vivax malaria.     

Influence of HLA-DRB-1 alleles on the production of antibody against CSP, MSP-1, AMA-1, and DBP in Brazilian individuals naturally infected with Plasmodium vivax

We evaluated the influence of allelic frequency of the human leukocyte antigen (HLA) -DRB1 on the acquisition of antibody response against malaria sporozoite and merozoite peptides in patients with Plasmodium vivax malaria acquired in endemic areas of Brazil. IgG antibodies were detected by enzyme-linked immunosorbent assay against four peptides of circumsporozoite protein (CSP) (amino, carboxyl, and VK210 and VK247 repeats) and peptides of merozoite surface protein 1 (MSP-1), apical membrane antigen 1 (AMA-1), and Duffy-binding protein (DBP). We found an association between HLA-DR3 and HLA-DR5 alleles and lack of antibody response to CSP amino terminal, as well as an association between HLA-DR3 and the highest antibody response to MSP1 (Pv200L). In conclusion, we suggest a potential regulatory role of the HLA-DRB1 alleles in the production of antibodies to a conserved region of P. vivax CSP and MSP1 in Brazilian population exposed to malaria.     

Toxoplasmosis in military personnel involved in jungle operations

Tropical diseases, mainly leishmaniasis and malaria, increased among Colombian military personnel due to intensive operations in the jungle in the last ten years; as a result the Colombian army developed important preventive strategies for malaria and leishmaniasis. However, no knowledge exists about toxoplasmosis, an emergent disease in military personnel. We compared the prevalence of IgG anti-Toxoplasma antibodies by ELISA and of parasitaemia by a real time PCR assay, in 500 professional soldiers that operated in the jungle with a group of 501 soldiers working in an urban zone (Bogotá). We found that the prevalence was significantly different between both groups of soldiers (80% in soldiers operating in jungle vs. 45% in urban soldiers, adjusted OR 11.4; CI 95%: 3.8-34; p<0.0001). All soldiers operating in the jungle drink unboiled and chlorine untreated lake or river water. In urban soldiers, these risk factors along with eating wild animal meat or eating tigrillo (little spotted cat) were significantly associated with a higher prevalence. Characteristic toxoplasmic choriorretinal lesions were found in 4 soldiers that operated in the jungle (0.8%) and in one urban soldier (0.19%). All soldiers before being deployed in jungle operations should be tested for Toxoplasma antibodies and to receive adequate health information about the routine use of personnel filters to purify their water for consumption.     

Evaluation of Cytotoxicity and Physicochemical Properties of Calcium Silicate-based Endodontic Sealer MTA Fillapex

IntroductionThe aim of the study was to evaluate the cytotoxicity, radiopacity, pH, and flow of a calcium silicate–based and an epoxy resin–based endodontic sealer, MTA Fillapex (Angelus, Londrina, PR, Brazil) and AH Plus (Dentsply, Konstanz, Germany), respectively.MethodsCytotoxicity, radiopacity, and flow evaluation were performed following ISO requirements. The pH level was measured at periods of 3, 24, 72, and 168 hours. Cytotoxicity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay to check the Balb/c 3T3 cells viability at 1- to 4-week periods. Data were statistically analyzed by analysis of variance and the Tukey test with a significance level of 5%.ResultsIn all tested periods, MTA Fillapex was more cytotoxic than AH Plus (P < .05). Although AH Plus presented higher radiopacity than MTA Fillapex (P < .05), both sealers showed minimum required values. MTA Fillapex presented alkaline pH in all experimental times, whereas AH Plus cement showed a slightly neutral pH and a flow significantly lower than that of MTA Fillapex (P < .05).ConclusionsAlthough MTA Fillapex was more cytotoxic than AH Plus, it showed suitable physicochemical properties for an endodontic sealer.     

Measurements of immune responses for establishing correlates of vaccine protection against HIV

Well-defined correlates of protective immunity are an essential component of rational vaccine development. Despite years of basic science and three HIV vaccine efficacy trials, correlates of immunological protection from HIV infection remain undefined. In December 2010, a meeting of scientists engaged in basic and translational work toward developing HIV-1 vaccines was convened. The goal of this meeting was to discuss current opportunities and optimal approaches for defining correlates of protection, both for ongoing and future HIV-1 vaccine candidates; specific efforts were made to engage young scientists. We discuss here the highlights from the meeting regarding the progress made and the way forward for a protective HIV-1 vaccine.     

Sulfonamide as amide isostere for fine-tuning the gelation properties of physical gels

(S)-2-Stearamidopentanedioic acid (C₁₈-Glu) is a known LMW gelator that forms supramolecular gels in a variety of solvents. In this work, we have carried out the isosteric substitution of the amide group by a sulfonamide moiety yielding the new isosteric gelator (S)-2-(octadecylsulfonamido)pentanedioic acid (Sulfo-Glu). The gelation ability and the key properties of the corresponding gels were compared in terms of gelation concentration, gel-to-sol transition temperature, mechanical properties, morphology, and gelation kinetics in several organic solvents and water. This comparison was also extended to (S)-2-(4-hexadecyl-1H-1,2,3-triazol-4-yl)pentanedioic acid (Click-Glu), which also constitutes an isostere of C₁₈-Glu. The stabilizing interactions were explored through computational calculations. In general, Sulfo-Glu enabled the formation of non-toxic gels at lower concentrations, faster, and with higher thermal-mechanical stabilities than those obtained with the other isosteres in most solvents. Furthermore, the amide-sulfonamide isosteric substitution also influenced the morphology of the gel networks as well as the release rate of an embedded antibiotic (vancomycin) leading to antibacterial activity in vitro against Staphylococcus aureus.

Amide–sulfonamide isosteric substitution in a low-molecular-weight gelator enables fine-tuning of its gelation ability and the properties of the corresponding supramolecular gels.