Quantitative PCR Evaluation of Cellular Immune Responses in Kenyan Children Vaccinated with a Candidate Malaria Vaccine

BACKGROUND: The T-cell mediated immune response plays a central role in the control of malaria after natural infection or vaccination. There is increasing evidence that T-cell responses are heterogeneous and that both the quality of the immune response and the balance between pro-inflammatory and regulatory T-cells determines the outcome of an infection. As Malaria parasites have been shown to induce immunosuppressive responses to the parasite and non-related antigens this study examined T-cell mediated pro-inflammatory and regulatory immune responses induced by malaria vaccination in children in an endemic area to determine if these responses were associated with vaccine immunogenicity. METHODS: Using real-time RT- PCR we profiled the expression of a panel of key markers of immunogenecity at different time points after vaccination with two viral vector vaccines expressing the malaria TRAP antigen (FP9-TRAP and MVA-TRAP) or following rabies vaccination as a control. PRINCIPAL FINDINGS: The vaccine induced modest levels of IFN-gamma mRNA one week after vaccination. There was also an increase in FoxP3 mRNA expression in both TRAP stimulated and media stimulated cells in the FFM ME-TRAP vaccine group; however, this may have been driven by natural exposure to parasite rather than by vaccination. CONCLUSION: Quantitative PCR is a useful method for evaluating vaccine induced cell mediated immune responses in frozen PBMC from children in a malaria endemic country. Future studies should seek to use vaccine vectors that increase the magnitude and quality of the IFN-gamma immune response in naturally exposed populations and should monitor the induction of a regulatory T cell response

Editorial: Why livestock genomics for developing countries offers opportunities for success.

Universidad Nacional Agraria La Molina. Escuela de Posgrado. Maestría en Producción AnimalThe Research Topic yielded 23 articles that are either review (five papers) or original research articles (18 papers) covering major livestock species kept in developing countries including cattle (seven papers), sheep (five papers), goats (three papers), and chickens (three papers). The manuscripts cover a broad range of genomic applications such as genomic selection/assisted breeding, genome-wide association analysis, diversity studies with a particular emphasis on adaptive genetic variation and signatures of selection analysis, and some elements of functional genomics using RNA sequencing and differential gene expression profiling. Whilst a broad range of genomic applications are covered, there is a bias toward genomic diversity studies, indicating the limited utility of other genomic applications due to inherent limitations to data collection and funding that characterize most developing countries, and are highlighted in some of the review article

The History of African Village Chickens: an Archaeological and Molecular Perspective

Abstract The history of the introduction and dispersal of village chickens across the African continent is a subject of intense debate and speculation among scholars. Here, we synthesize and summarise the current scientific genetic and nongenetic knowledge in relation to the history of the species on the continent. Sociocultural, linguistic, archaeological and historic data all suggest a complex history for the species in Africa, characterized by multiple maritime and/or terrestrial introductions over time and several dispersal routes towards and within Africa. Molecular genetics information supports these observations and in addition suggests possible Asian centers of origin for African domestic chickens, including South Asia and Island Southeast Asia. However, both sets of data were until now too limited in their geographic scope, both within Africa and in comparison with chickens from Asia, to unravel the history of the species in detail. We anticipate that further continent-wide studies combining archaeological, ancient and/or modern genetic information may shed new insights on Afr Archaeol Rev (2013) 30:97-11

Targeting strategic investment in livestock development as a vehicle for rural livelihoods

The purpose of this report is first to provide evidence of the role of livestock in rural livelihoods in Sub-Saharan Africa and South Asia. Further, the report aims to identify opportunities for investments that build on that evidence and hold promise for improving and sustaining the livelihoods of smallholder livestock producers and their rural communities in developing countries. This analysis is presented in order to support the decision making of those public and private development investors, and policy makers, for whom improved rural livelihoods is a key objective. The report is presented in two parts. Part 1 comprises summaries of in-depth analysis of key issues central to the role of livestock and rural livelihoods, each of which brings together a wide range of available data to inform the topic. Part 2 then uses the information generated and presented in Part 1 and through a conceptual framework for guiding pro-poor livestock investment, identifies the key value chains or livestock systems and regions that are demonstrated by the evidence to offer livelihood opportunities, and some initial description of best bet types of interventions

Correlations between three ELISA protocols measurements of RTS,S/AS01-induced anti-CSP IgG antibodies

Background RTS,S/AS01 induced anti-circumsporozoite protein (CSP) IgG antibodies are associated with the vaccine efficacy. There is currently no international standardisation of the assays used in the measurement of anti-CSP IgG antibody concentrations for use in evaluations of the vaccine’s immunogenicity and/or efficacy. Here, we compared the levels of RTS,S/AS01 induced anti-CSP IgG antibodies measured using three different enzyme-Linked ImmunoSorbent Assays (ELISA). Methods 196 plasma samples were randomly selected from the 447 samples collected during the RTS,S/AS01 phase IIb trial in 2007 from Kenyan children aged between 5–17 months. The vaccine-induced anti-CSP IgG antibodies were then measured using two independently developed ELISA protocols (‘Kilifi-RTS,S’ and ‘Oxford-R21’) and compared to the results from the reference ‘Ghent-RTS,S’ protocol for the same participants. For each pair of protocols, a deming regression model was fitted. Linear equations were then derived to aid in conversions into equivalent ELISA units. The agreement was assessed using Bland and Altman method. Findings The anti-CSP IgG antibodies measured from the three ELISA protocols were in agreement, and were positively and linearly correlated; ‘Oxford’ and ‘Kilifi’ r = 0.93 (95% CI 0.91–0.95), ‘Oxford’ and ‘Ghent’ r = 0.94 (95% CI: 0.92–0.96), and ‘Kilifi’ and ‘Ghent’ r = 0.97 (95% CI: 0.96–0.98), p<0.0001 for all correlations. Conclusions With the linearity, agreement and correlations established between the assays, conversion equations can be applied to convert results into equivalent units, enabling comparisons of immunogenicities across different vaccines of the same CSP antigens. This study highlights the need for the international harmonisation of anti-CSP antibody measurements

Circumsporozoite-specific T cell responses in children vaccinated with RTS,S/AS01 E and protection against P falciparum clinical malaria

Background:RTS,S/AS01E is the lead candidate pre-erythrocytic malaria vaccine. In Phase IIb field trials the safety profile was acceptable and the efficacy was 53% (95%CI 31%&ndash;72%) for protecting children against clinical malaria caused by P. falciparum. We studied CS-specific T cell responses in order to identify correlates of protection.Methods and Findings:We used intracellular cytokine staining (for IL2, IFN&gamma;, and TNF&alpha;), ex-vivo ELISPOTs (IFN&gamma; and IL2) and IFN&gamma; cultured ELISPOT assays to characterize the CS-specific cellular responses in 407 children (5&ndash;17 months of age) in a phase IIb randomized controlled trial of RTS,S/AS01E (NCT00380393). RTS,S/ AS01E vaccinees had higher frequencies of CS-specific CD4+ T cells producing IFN&gamma;, TNF&alpha; or IL2 compared to control vaccinees. In a multivariable analysis TNF&alpha;+ CD4+ T cells were independently associated with a reduced risk for clinical malaria among RTS,S/AS01E vaccinees (HR = 0.64, 95%CI 0.49&ndash;0.86, p = 0.002). There was a non-significant tendency towards reduced risk among control vaccinees (HR = 0.80, 95%CI 0.62&ndash;1.03, p = 0.084), albeit with lower CS-specific T cell frequencies and higher rates of clinical malaria. When data from both RTS,S/AS01E vaccinees and control vaccinees were combined (with adjusting for vaccination group), the HR was 0.74 (95%CI 0.62&ndash;0.89, p = 0.001). After a Bonferroni correction for multiple comparisons (n-18), the finding was still significant at p = 0.018. There was no significant correlation between cultured or ex vivo ELISPOT data and protection from clinical malaria. The combination of TNF&alpha;+ CD4+ T cells and anti-CS antibody statistically accounted for the protective effect of vaccination in a Cox regression model.Conclusions:RTS,S/AS01E induces CS-specific Th1 T cell responses in young children living in a malaria endemic area. The combination of anti-CS antibody concentrations titers and CS-specific TNF&alpha;+ CD4+ T cells could account for the level of protection conferred by RTS,S/AS01E. The correlation between CS-specific TNF&alpha;+ CD4+ T cells and protection needs confirmation in other datasets

Hematological profile of East African Short-Horn Zebu calves: From birth to 51 weeks of age

This paper is the first attempt to accurately describe the hematological parameters for any African breed of cattle, by capturing the changes in these parameters over the first 12 months of an animal’s life using a population based sample of calves reared under field conditions and natural disease challenge. Using a longitudinal study design, a stratified clustered random sample of newborn calves was recruited into the Infectious Diseases of East African Livestock (IDEAL) study and monitored at 5-weekly intervals until 51 weeks of age. The blood cell analysis performed at each visit included: packed cell volume; red cell count; red cell distribution width; mean corpuscular volume; mean corpuscular hemoglobin concentration; hemoglobin concentration; white cell count; absolute lymphocyte, eosinophil, monocyte, and neutrophil counts; platelet count; mean platelet volume; and total serum protein. The most significant age-related change in the red cell parameters was a rise in red cell count and hemoglobin concentration during the neonatal period. This is in contrast to what is reported for other ruminants, including European cattle breeds where the neonatal period is marked by a fall in the red cell parameters. There is a need to establish breed specific reference ranges for blood parameters for indigenous cattle breeds. The possible role of the postnatal rise in the red cell parameters in the adaptability to environmental constraints and innate disease resistance warrants further research into the dynamics of blood cell parameters of these breed

Analysis of genome-wide structure, diversity and fine mapping of Mendelian traits in traditional and village chickens

Extensive phenotypic variation is a common feature among village chickens found throughout much of the developing world, and in traditional chicken breeds that have been artificially selected for traits such as plumage variety. We present here an assessment of traditional and village chicken populations, for fine mapping of Mendelian traits using genome-wide single-nucleotide polymorphism (SNP) genotyping while providing information on their genetic structure and diversity. Bayesian clustering analysis reveals two main genetic backgrounds in traditional breeds, Kenyan, Ethiopian and Chilean village chickens. Analysis of linkage disequilibrium (LD) reveals useful LD (r(2)⩾0.3) in both traditional and village chickens at pairwise marker distances of ∼10 Kb; while haplotype block analysis indicates a median block size of 11–12 Kb. Association mapping yielded refined mapping intervals for duplex comb (Gga 2:38.55–38.89 Mb) and rose comb (Gga 7:18.41–22.09 Mb) phenotypes in traditional breeds. Combined mapping information from traditional breeds and Chilean village chicken allows the oocyan phenotype to be fine mapped to two small regions (Gga 1:67.25–67.28 Mb, Gga 1:67.28–67.32 Mb) totalling ∼75 Kb. Mapping the unmapped earlobe pigmentation phenotype supports previous findings that the trait is sex-linked and polygenic. A critical assessment of the number of SNPs required to map simple traits indicate that between 90 and 110K SNPs are required for full genome-wide analysis of haplotype block structure/ancestry, and for association mapping in both traditional and village chickens. Our results demonstrate the importance and uniqueness of phenotypic diversity and genetic structure of traditional chicken breeds for fine-scale mapping of Mendelian traits in the species, with village chicken populations providing further opportunities to enhance mapping resolutions