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New findings of widespread neglected diseases among the poor living in wealthy group of 20 (G20) economies and the concept of “blue marble health” offer innovative mechanisms for financing urgently new vaccines, especially for vector-borne neglected tropical diseases (NTDs). This approach could complement or parallel a recently suggested global vaccine development fund for pandemic threats.
Despite the generally accepted immunostimulatory effect of Toll-Like Receptor 4 (TLR4) agonists and their value as vaccine adjuvants, there remains a demand for fast and easy quantification assays for these TLR4 agonists in order to accelerate and improve vaccine formulation studies. A new medium-throughput method was developed for the quantification of the TLR4 agonist, E6020, independent of the...
Helminth infections are the most common afflictions of humankind, affecting almost every single person living in profound poverty. Through mass drug administration (MDA) we have seen sharp declines in the global prevalence of some helminth infections, including lymphatic filariasis, onchocerciasis, and ascariasis. However, since 1990, there has been no appreciable decrease in the global prevalence...
A number of leishmaniasis vaccine candidates are at various stages of pre-clinical and clinical development. Leishmaniasis is a vector-borne neglected tropical disease (NTD) caused by a protozoan parasite of the genus Leishmania and transmitted to humans by the bite of a sand fly. Visceral leishmaniasis (VL, kala-azar) is a high mortality NTD found mostly in South Asia and East Africa, while cutaneous...
A human hookworm vaccine is under development and in clinical trials in Africa and the Americas. The vaccine contains the Na-APR-1 and Na-GST-1 antigens. It elicits neutralizing antibodies that interfere with establishment of the adult hookworm in the gut and the ability of the parasite to feed on blood. The vaccine target product profile is focused on the immunization of children to prevent hookworm...
•Chagas disease is responsible for 10,600 deaths and 0.6 million DALYS annually.•Chemotherapy requires timely diagnosis and long-term treatment.•Vaccine-linked chemotherapy will combine therapeutic vaccine with drugs.•Recombinant protein-based and DNA-based vaccine candidates are reviewed.
Several candidate human schistosomiasis vaccines are in different stages of preclinical and clinical development. The major targets are Schistosoma haematobium (urogenitial schistosomiasis) and Schistosoma mansoni (intestinal schistosomiasis) that account for 99% of the world's 252 million cases, with 90% of these cases in Africa. Two recombinant S. mansoni vaccines – Sm-TSP-2 and Sm-14 are in Phase...
Although mass drug administration (MDA) has helped reduce morbidity attributed to soil-transmitted helminth infections in children, its limitations for hookworm infection have motivated the development of a human hookworm vaccine to both improve morbidity control and ultimately help block hookworm transmission leading to elimination. However, the potential economic and epidemiologic impact of a preventive...
The Tc24 calcium binding protein from the flagellar pocket of Trypanosoma cruzi is under evaluation as a candidate vaccine antigen against Chagas disease. Previously, a DNA vaccine encoding Tc24 was shown to be an effective vaccine (both as a preventive and therapeutic intervention) in mice and dogs, as evidenced by reductions in T. cruzi parasitemia and cardiac amastigotes, as well as reduced cardiac...
Hookworm infection is one of the world's most common neglected tropical diseases and a leading cause of iron deficiency anemia in low- and middle-income countries. A Human Hookworm Vaccine is currently being developed by the Sabin Vaccine Institute and is in phase 1 clinical testing. The candidate vaccine is comprised of two recombinant antigens known as Na-GST-1 and Na-APR-1, each of which is an...
Cutaneous leishmaniasis (CL) and its associated complications, including mucocutaneous leishmaniasis (MCL) and diffuse CL (DCL) have emerged as important neglected tropical diseases in Latin America, especially in areas associated with human migration, conflict, and recent deforestation. Because of the limitations of current chemotherapeutic approaches to CL, MCL, and DCL, several prototype vaccines...
Necator americanus Ancylostoma Secreted Protein-2 (Na-ASP-2) is a leading larval-stage hookworm vaccine candidate. Recombinant Na-ASP-2 was expressed in Pichia pastoris and formulated with Alhydrogel ® . In a phase 1 trial, 36 healthy adults without history of hookworm infection were enrolled into 1 of 3 dose cohorts (n=12 per cohort) and randomized to receive intramuscular injections of either...
The neglected tropical diseases represent a group of parasitic and bacterial diseases, occurring primarily in rural areas or impoverished urban areas of developing countries. Because of their chronic and stigmatizing character and their impact on child development, pregnancy outcomes, and worker productivity, the neglected tropical diseases are considered poverty-promoting conditions. Through the...
While X-irradiated live parasites are not an acceptable proposition for human vaccination, they offer a ready experimental system to explore mechanisms by which immunity against hookworm infection may be induced in humans. As such, we sought to further elucidate the details of this highly protective immune response induced by the irradiated vaccine in canids, with special emphasis on the cellular...
The ASP-2 protein secreted by infective larvae of the human hookworm, Necator americanus, is under development as a recombinant vaccine. Recombinant Na-ASP-2 was expressed in Pichia pastoris, and the purified protein was characterized. At the 60L scale, the 21.3kDa recombinant protein was produced at a yield of 0.4g/L. When formulated with Alhydrogel ® and injected into rats to determine immunological...
Syrian Golden hamsters were vaccinated with the recombinant fusion proteins Ay-ASP-2 and Ay-MTP-1 from the infective larvae of the hookworm Ancylostoma ceylanicum. Vaccines comprised each antigen alone or the combination of the two proteins. All vaccinated group developed high antibody titers (>1:40,000); coadministration of a second antigen did not significantly affect the magnitude of the antibody...
Vaccination of mice with alum-precipitated recombinant Ancylostoma secreted protein-1 from the canine hookworm Ancylostoma caninum (Ac-ASP-1) results in protection against A. caninum larval challenge. Vaccine protection is manifested by host reductions in hookworm burden compared to control mice. The goal of this study was to determine whether ASP antigens cloned and expressed from different hookworm...
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