Glycoconjugate vaccines provide effective prophylaxis against bacterial infections. To date, however, no commercial vaccine has been available in which the key carbohydrate antigens are produced synthetically. We describe the large-scale synthesis, pharmaceutical development, and clinical evaluation of a conjugate vaccine composed of a synthetic capsular polysaccharide antigen of Haemophilus influenzae type b (Hib). The vaccine was evaluated in clinical trials in Cuba and showed long-term protective antibody titers that compared favorably to licensed products prepared with the Hib polysaccharide extracted from bacteria. This demonstrates that access to synthetic complex carbohydrate-based vaccines is feasible and provides a basis for further development of similar approaches for other human pathogens.
The ookinete surface proteins (P25 and P28) are proven antimalarial transmission-blocking vaccine targets, yet their biological functions are unknown. By using single (Sko) and double gene knock-out (Dko) Plasmodium berghei parasites, we show that P25 and P28 share multiple functions during ookinete/oocyst development. In the midgut of mosquitoes, the formation of ookinetes lacking both proteins (Dko parasites) is signi®cantly inhibited due to decreased protection against lethal factors, including protease attack. In addition, Dko ookinetes have a much reduced capacity to traverse the midgut epithelium and to transform into the oocyst stage. P25 and P28 are partially redundant in these functions, since the ef®ciency of ookinete/oocyst development is only mildly compromised in parasites lacking either P25 or P28 (Sko parasites) compared with that of Dko parasites. The fact that Sko parasites are ef®ciently transmitted by the mosquito is a compelling reason for including both target antigens in transmission-blocking vaccines.
Nucleotide sequences of mitochondrial DNA (mtDNA) cytochrome B gene (1140 bp) and control region (707 bp) were used to determine the phylogenetic relationships among 51 pig samples representing ancient and current varieties of Iberian pigs (26), Spanish wild boars (seven) and other domestic pigs (18) of cosmopolitan (Duroc, Large White, Landrace, Pietrain and Meishan) and local (Spotted Black Jabugo, Basque and Mangalitza) breeds. A neighbour-joining tree constructed from pairwise distances provide evidence of the European origin of both Iberian pigs and Spanish wild boars. The introgression of Asian mtDNA haplotypes in the genetic pool of the Iberian breed seems unlikely. Four estimates of sequence divergence between European and Asian clades were calculated from the two main domains of the D-loop region and the synonymous and nonsynonymous nucleotide substitutions in the cytochrome B gene. The time since the divergence of pig ancestors was estimated at about 600,000 years before present.
The Iberian breed is the most important pig population of the Mediterranean type. The genetic structure of two strains (Torbiscal and Guadyerbas) and three varieties (Retinto, Entrepelado and Lampiñ o) of this breed was studied using 173 pigs genotyped for 36 microsatellites. In addition, 40 pigs of the related Duroc breed were also analysed. In the 1960s, the Iberian breed's numbers were severely reduced by disease, due to economic change and to crossbreeding. Varieties are in danger of disappearance or blending. A new conservation strategy is required. An analysis was performed that allows us to ascertain the loss or gain of genetic diversity if one or several subpopulations are removed. The results are compared with those using the Weitzman method. The two methodologies produce conservation priorities that are completely different, the reason being that the Weitzman method does not take into account the within-population genetic diversity. We apply optimal contribution theory and a new procedure for cluster analysis, and discuss their value in the general framework of the problems of setting of priorities and tactics for the conservation of genetic resources.
The pig, Sus scrofa, is a foreign species to the American continent. Although pigs originally introduced in the Americas should be related to those from the Iberian Peninsula and Canary islands, the phylogeny of current creole pigs that now populate the continent is likely to be very complex. Because of the extreme climates that America harbors, these populations also provide a unique example of a fast evolutionary phenomenon of adaptation. Here, we provide a genome wide study of these issues by genotyping, with a 60k SNP chip, 206 village pigs sampled across 14 countries and 183 pigs from outgroup breeds that are potential founders of the American populations, including wild boar, Iberian, international and Chinese breeds. Results show that American village pigs are primarily of European ancestry, although the observed genetic landscape is that of a complex conglomerate. There was no correlation between genetic and geographical distances, neither continent wide nor when analyzing specific areas. Most populations showed a clear admixed structure where the Iberian pig was not necessarily the main component, illustrating how international breeds, but also Chinese pigs, have contributed to extant genetic composition of American village pigs. We also observe that many genes related to the cardiovascular system show an increased differentiation between altiplano and genetically related pigs living near sea level.
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