Design and immunological evaluation of two-component protein nanoparticle vaccines for East Coast fever.

Nanoparticle vaccines usually prime stronger immune responses than soluble antigens. Within this class of subunit vaccines, the recent development of computationally designed self-assembling two-component protein nanoparticle scaffolds provides a powerful and versatile platform for displaying multiple copies of one or more antigens. Here we report the generation of three different nanoparticle immunogens displaying 60 copies of p67C, an 80 amino acid polypeptide from a candidate vaccine antigen of Theileria parva, and their immunogenicity in cattle. p67C is a truncation of p67, the major surface protein of the sporozoite stage of T. parva, an apicomplexan parasite that causes an often-fatal bovine disease called East Coast fever (ECF) in sub-Saharan Africa. Compared to I32-19 and I32-28, we found that I53-50 nanoparticle scaffolds displaying p67C had the best biophysical characteristics. p67C-I53-50 also outperformed the other two nanoparticles in stimulating p67C-specific IgG1 and IgG2 antibodies and CD4+ T-cell responses, as well as sporozoite neutralizing capacity. In experimental cattle vaccine trials, p67C-I53-50 induced significant immunity to ECF, suggesting that the I53-50 scaffold is a promising candidate for developing novel nanoparticle vaccines. To our knowledge this is the first application of computationally designed nanoparticles to the development of livestock vaccines.

The prevalence of intestinal parasites and associated risk factors in school-going children from informal settlements in Nakuru town, Kenya.

BACKGROUND: Intestinal parasites are a major public health problem in the developing world and have attracted increasing levels of interest from health researchers over the past decade. Epidemiology-based studies have shown that the prevalence of intestinal parasites is high and they frequently recur in regions with poor sanitation and inadequate sewerage facilities. In this study, we determined the prevalence of intestinal parasites, their egg intensities per sample, and associated risk factors in an informal settlement. METHODS: This was a cross-sectional study conducted in three randomly selected public primary schools located in the informal settlements of Nakuru town. A total of 248 stool samples were collected from asymptomatic pupils and screened, using the Kato Katz technique, for infections caused by soil-transmitted helminths (STH). A random subset of stool samples (n=96) was also screened by polymerase chain reaction (PCR) to detect intestinal protozoa. Socio-demographic variables were collected using a pre-tested structured questionnaire; these data were analysed to identify risk factors for infection. RESULTS: The overall prevalence of intestinal parasites was 17.3% (43/248 pupils). The overall prevalence of both STH and intestinal protozoan parasites was 1.2% and 41.7%, respectively. The most commonly diagnosed STH infection was Trichuris trichiura (1.2%), followed by hookworms (0.4%) and Ascaris lumbricoides (0.4%). The prevalence of intestinal protozoan parasites ranged from 0% to 38.5% and included Entamoeba histolytica, Entamoeba hartmanni, Entamoeba dispar, Giardia intestinalis, and Entamoeba coli. All infections were light, with an egg intensity <100 for each of the STH infections. The prevalence of multiple infections, including intestinal protozoan parasites, was 5.2% (n=5) and 0.4% (n=1) for STH in the subset samples. Finally, our analysis identified several significant risk factors for intestinal parasitic infections, including goat rearing (p=0.046), living in a home with an earthen floor (p=0.022), the number of rooms in the household (p=0.035), and the source of food (p=0.016). CONCLUSION: The low prevalence of intestinal parasites in the informal settlements of Nakuru may be attributed to improvements in hygiene and sanitation, deworming, and general good health practices that are facilitated by the Department of Public Health.