Limited antigenic diversity of Plasmodium falciparum apical membrane antigen 1 supports the development of effective multi-allele vaccines

BackgroundPolymorphism in antigens is a common mechanism for immune evasion used by many important pathogens, and presents major challenges in vaccine development. In malaria, many key immune targets and vaccine candidates show substantial polymorphism. However, knowledge on antigenic diversity of key antigens, the impact of polymorphism on potential vaccine escape, and how sequence polymorphism relates to antigenic differences is very limited, yet crucial for vaccine development. Plasmodium falciparum apical membrane antigen 1 (AMA1) is an important target of naturally-acquired antibodies in malaria immunity and a leading vaccine candidate. However, AMA1 has extensive allelic diversity with more than 60 polymorphic amino acid residues and more than 200 haplotypes in a single population. Therefore, AMA1 serves as an excellent model to assess antigenic diversity in malaria vaccine antigens and the feasibility of multi-allele vaccine approaches. While most previous research has focused on sequence diversity and antibody responses in laboratory animals, little has been done on the cross-reactivity of human antibodies.MethodsWe aimed to determine the extent of antigenic diversity of AMA1, defined by reactivity with human antibodies, and to aid the identification of specific alleles for potential inclusion in a multi-allele vaccine. We developed an approach using a multiple-antigen-competition enzyme-linked immunosorbent assay (ELISA) to examine cross-reactivity of naturally-acquired antibodies in Papua New Guinea and Kenya, and related this to differences in AMA1 sequence.ResultsWe found that adults had greater cross-reactivity of antibodies than children, although the patterns of cross-reactivity to alleles were the same. Patterns of antibody cross-reactivity were very similar between populations (Papua New Guinea and Kenya), and over time. Further, our results show that antigenic diversity of AMA1 alleles is surprisingly restricted, despite extensive sequence polymorphism. Our findings suggest that a combination of three different alleles, if selected appropriately, may be sufficient to cover the majority of antigenic diversity in polymorphic AMA1 antigens. Antigenic properties were not strongly related to existing haplotype groupings based on sequence analysis.ConclusionsAntigenic diversity of AMA1 is limited and a vaccine including a small number of alleles might be sufficient for coverage against naturally-circulating strains, supporting a multi-allele approach for developing polymorphic antigens as malaria vaccines

Enhanced Antioxidant Capacity Following Selenium Supplemented Antimalarial Therapy in Plasmodium berghei Infected Mice

The effect of the co-administration of artemether, lumefantrine and selenium was studied in mice infected with Plasmodium bergheiparasite. The mice were divided into seven groups of six animals per group.All groups except A were parasitized. Group A (unparasitized/untreated) and B (parasitized/untreated) served as the positive and negative control respectively, these were administered with olive oil. Animals in groups C and D were treated with 8 and 48 mg/kg/bw of artemether and lumefantrine respectively while group E was treated with a combination of artemether and lumefantrine (8: 48 mg/kg/bw). Animals in group F were treated with 0.945 mg/kg/bw of selenium only and group G was treated with a combination of artemether, lumefantrine and selenium (8:48:0.945 mg/kg/bw). All the treatment was done for a three day period. These animals were subsequently anaesthetized and the organs were excised. Homogenates were prepared for aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total protein, reduced Glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) assays. The results showed a significant (p<0.05) difference in the levels of ALP and MDA in group B, while a significant difference was observed in the levels of ALP, total protein, CAT and MDA in group G when compared with the parasitized group. Histopathological analysis showed no presence of inflammatory cells in group G when compared with group B. It may be concluded that the combination of artemether, lumefantrine and selenium showed a more potent effect against the parasite than the group treated with artemether and lumefantrine, thus, helps to combat post-infection oxidative stress in susceptible cells

Determination of Prediction Equations to Estimate Body Condition Score From Body Size and Testicular Traits of Yankasa Rams

The study was aimed to develop prediction models using stepwise multiple linear regressionanalysis for estimating the body condition score (BCS) from the body weight (BW), testicular length(TL), testicular diameter (TD) and scrotal circumference (SC) of indigenous Yankasa rams. Data wereobtained from 120 randomly selected rams with approximately two and half years of age, from differentextensively managed herds in Nasarawa State, Nigeria. Although pairwise phenotypic correlationsindicated strong association (P<0.01) among the measured variables, there was collinearity problembetween BW and SC as revealed by the variance inflation factors (VIF) and tolerance valves (T). TheVIT was higher than 10 (VIF = 19.45 and 16.65 for BW and SC, respectively). The Twas smaller than0.1 (T = 0.05 and 0.06 in BW and SC, respectively). BW was retained among the collinear variables, andwas singly accounted for 83.7% of the variation in BCS. However, a slight improvement was obtainedfrom the prediction of BCS from BW and TL [coefficient of determination (R2), adjusted R2 and rootmean squares error (RMSE) were 85.3%, 85.1% and 0.305, respectively]. The prediction of the BCS ofYankasa rams from BW and testicular measurements could therefore be a potential tool for sustainableproduction and improvement of small ruminants in Nigeria

Cardiovascular Risk Factors in a Suburban Community in Nigeria

The burden of hypertension, a silent killer, continues to increase in low- and middle-income countries. This study evaluated blood pressure (BP) in healthy adults to determine their risk of developing hypertension and to reduce associatedmorbidity of the disease. Overall, 182 subjects aged >16 years participated in the study. Systolic (SBP) and diastolic blood pressure (DBP) was measured after a resting period usingmercury sphygmomanometer. Randomblood glucose (RBG) concentration was also determined. Regression models were used to determine risk of high BP wit

Identifying genomic and metabolic features that can underlie early successional and opportunistic lifestyles of human gut symbionts

We lack a deep understanding of genetic and metabolic attributes specializing in microbial consortia for initial and subsequent waves of colonization of our body habitats. Here we show that phylogenetically interspersed bacteria in Clostridium cluster XIVa, an abundant group of bacteria in the adult human gut also known as the Clostridium coccoides or Eubacterium rectale group, contains species that have evolved distribution patterns consistent with either early successional or stable gut communities. The species that specialize to the infant gut are more likely to associate with systemic infections and can reach high abundances in individuals with Inflammatory Bowel Disease (IBD), indicating that a subset of the microbiota that have adapted to pioneer/opportunistic lifestyles may do well in both early development and with disease. We identified genes likely selected during adaptation to pioneer/opportunistic lifestyles as those for which early succession association and not phylogenetic relationships explain genomic abundance. These genes reveal potential mechanisms by which opportunistic gut bacteria tolerate osmotic and oxidative stress and potentially important aspects of their metabolism. These genes may not only be biomarkers of properties associated with adaptation to early succession and disturbance, but also leads for developing therapies aimed at promoting reestablishment of stable gut communities following physiologic or pathologic disturbances

Conflict In Couples Therapy: Enhancing Relationships Through A Video Tape Feedback Intervention Intending To Develop Effective Conflict Communication Skills

The current study examined the effectiveness of a Gottman-based intervention (2007) aimed to increase effective conflict communication. The study utilized a single case design to examine two couple\u27s conflict interactions through the use of a video tape feedback intervention and psychoeducation about effective and ineffective conflict communication. Couples completed a four week pre-test measurement phase, three sessions of video tape feedback, and four week post-test measurement phase. Through visual analysis, the study investigated the effect that this conflict management intervention had on relational satisfaction and adjustment, life satisfaction, overall distress levels, and conflict abilities. Findings of the current study were mixed. Overall, the use of a video tape feedback intervention had a positive impact on couples conflict abilities. However, there was less support found for the impact on relationship satisfaction, overall satisfaction, and overall well-being. Implications and considerations for future research are discussed

Quantized reduction as a tensor product

Symplectic reduction is reinterpreted as the composition of arrows in the category of integrable Poisson manifolds, whose arrows are isomorphism classes of dual pairs, with symplectic groupoids as units. Morita equivalence of Poisson manifolds amounts to isomorphism of objects in this category. This description paves the way for the quantization of the classical reduction procedure, which is based on the formal analogy between dual pairs of Poisson manifolds and Hilbert bimodules over C*-algebras, as well as with correspondences between von Neumann algebras. Further analogies are drawn with categories of groupoids (of algebraic, measured, Lie, and symplectic type). In all cases, the arrows are isomorphism classes of appropriate bimodules, and their composition may be seen as a tensor product. Hence in suitable categories reduction is simply composition of arrows, and Morita equivalence is isomorphism of objects.Comment: 44 pages, categorical interpretation adde

Efficiency of Histidine Rich Protein II-Based Rapid Diagnostic Tests for Monitoring Malaria Transmission Intensities in an Endemic Area

In recent years there has been a global decrease in the prevalence of malaria due to scaling up of control measures, hence global control efforts now target elimination and eradication of the disease. However, a major problem associated with elimination is asymptomatic reservoir of infection especially in endemic areas. This study aims to determine the efficiency of histidine rich protein II (HRP-2) based rapid diagnostic tests (RDT) for monitoring transmission intensities in an endemic community in Nigeria during the pre-elimination stage. Plasmodium falciparum asymptomatic malaria infection in healthy individuals and symptomatic cases were detected using HRP-2. RDT negative tests were re-checked by microscopy and by primer specific PCR amplification of merozoite surface protein 2 (msp-2) for asexual parasites and Pfs25 gene for gametocytes in selected samples to detect low level parasitemia undetectable by microscopy. The mean age of the study population (n=280) was 6.12 years [95% CI 5.16 – 7.08, range 0.5 – 55], parasite prevalence was 44.6% and 36.3% by microscopy and RDT respectively (p =0.056). The parasite prevalence of 61.5% in children aged >2 – 10 years was significantly higher than 3.7% rate in adults >18years (p < 0.0001, χ2 = 60.45). RDT detected additional 29.6% asymptomatic cases but a lower specificity of 68.8% in symptomatic carriers. In 15 selected RDT positive samples, only 6 were positive by PCR and no gametocyte was detected. The results indicate that HRP-2 RDTs are a vital tool for understanding transmission dynamics and detecting immune-suppressed, recent and asymptomatic infections, thus crucial to tackle low level transmission and eliminating malaria in endemic areas