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Vaccines Jul 2023Onchocerciasis remains a debilitating neglected tropical disease. Due to the many challenges of current control methods, an effective vaccine against the causative agent...
Onchocerciasis remains a debilitating neglected tropical disease. Due to the many challenges of current control methods, an effective vaccine against the causative agent is urgently needed. Mice and cynomolgus macaque non-human primates (NHPs) were immunized with a vaccine consisting of a fusion of two protein antigens, -103 and -RAL-2 (-FUS-1), and three different adjuvants: Advax-CpG, alum, and AlT4. All vaccine formulations induced high antigen-specific IgG titers in both mice and NHPs. Challenging mice with L3 contained within subcutaneous diffusion chambers demonstrated that -FUS-1/Advax-CpG-immunized animals developed protective immunity, durable for at least 11 weeks. Passive transfer of sera, collected at several time points, from both mice and NHPs immunized with -FUS-1/Advax-CpG transferred protection to naïve mice. These results demonstrate that -FUS-1 with the adjuvant Advax-CpG induces durable protective immunity against in mice and NHPs that is mediated by vaccine-induced humoral factors.
PubMed: 37515028
DOI: 10.3390/vaccines11071212 -
Pathogens (Basel, Switzerland) Jul 2023Onchocerciasis is a neglected tropical disease targeted for elimination using ivermectin mass administration. Ivermectin kills the microfilariae and temporarily arrests...
Onchocerciasis is a neglected tropical disease targeted for elimination using ivermectin mass administration. Ivermectin kills the microfilariae and temporarily arrests microfilariae production by the macrofilariae. We genotyped 436 microfilariae from 10 people each in Ituri, Democratic Republic of the Congo (DRC), and Maridi County, South Sudan, collected before and 4-5 months after ivermectin treatment. Population genetic analyses identified 52 and 103 mitochondrial DNA haplotypes among the microfilariae from DRC and South Sudan, respectively, with few haplotypes shared between people. The percentage of genotype-based correct assignment to person within DRC was ~88% and within South Sudan ~64%. Rarefaction and extrapolation analysis showed that the genetic diversity in DRC, and even more so in South Sudan, was captured incompletely. The results indicate that the per-person adult worm burden is likely higher in South Sudan than DRC. Analyses of haplotype data from a subsample ( = 4) did not discriminate genetically between pre- and post-treatment microfilariae, confirming that post-treatment microfilariae are not the result of new infections. With appropriate sampling, mitochondrial haplotype analysis could help monitor changes in the number of macrofilariae in a population as a result of treatment, identify cases of potential treatment failure, and detect new infections as an indicator of continuing transmission.
PubMed: 37513818
DOI: 10.3390/pathogens12070971 -
The American Journal of Tropical... Oct 2023To implement the appropriate strategies for scale-up interventions to eliminate onchocerciasis without severe adverse events, clinical and biological factors associated...
To implement the appropriate strategies for scale-up interventions to eliminate onchocerciasis without severe adverse events, clinical and biological factors associated with loiasis were analyzed in onchocerciasis-endemic areas. Blood was collected from volunteers after examination by a physician. Detection of microfilariae and measurement of Ov16 IgG4 were performed using direct microscopic examination of blood and onchocerciasis rapid test detection, respectively. Areas with sporadic, hypoendemic, and hyperendemic onchocerciasis endemicity were found. Participants with microfilaremia were considered microfilaremic, and those without microfilaremia were seen as amicrofilaremic. Of the 471 study participants, 40.5% (n = 191) had microfilariae. Among them, Mansonella spp. was the most common (78.2%, n = 147), followed by Loa loa (41.4%, n = 79). The association between the two species represented 18.3% (n = 35). The specific immunoglobulins of Onchocerca volvulus were detected in 24.2% of participants (n = 87/359). Overall prevalence of L. loa was 16.8%. Hypermicrofilaremia was found in 3% (N = 14), and one participant had more than 30,000 microfilaremiae per milliliter. The frequency of L. loa did not vary according to the level of onchocerciasis transmission. Pruritus was the most common clinical sign (60.5%, n = 285) reported, mainly in microfilaremic participants (72.2%, n = 138/191). The prevalence of L. loa microfilaria in the study population was below the threshold at risk for the occurrence of serious side effects due to ivermectin. Clinical manifestations frequently observed could be exacerbated by microfilaremia in areas where onchocerciasis transmission is high.
Topics: Animals; Humans; Onchocerciasis; Loiasis; Gabon; Biological Factors; Endemic Diseases; Ivermectin; Loa; Microfilariae
PubMed: 37339766
DOI: 10.4269/ajtmh.22-0558