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Review
. 2011 Jan;239(1):237-70.
doi: 10.1111/j.1600-065X.2010.00976.x.

Vaccines to combat the neglected tropical diseases

Affiliations
Review

Vaccines to combat the neglected tropical diseases

Jeffrey M Bethony et al. Immunol Rev. 2011 Jan.

Abstract

The neglected tropical diseases (NTDs) represent a group of parasitic and related infectious diseases such as amebiasis, Chagas disease, cysticercosis, echinococcosis, hookworm, leishmaniasis, and schistosomiasis. Together, these conditions are considered the most common infections in low- and middle-income countries, where they produce a level of global disability and human suffering equivalent to better known conditions such as human immunodeficiency virus/acquired immunodeficiency syndrome and malaria. Despite their global public health importance, progress on developing vaccines for NTD pathogens has lagged because of some key technical hurdles and the fact that these infections occur almost exclusively in the world's poorest people living below the World Bank poverty line. In the absence of financial incentives for new products, the multinational pharmaceutical companies have not embarked on substantive research and development programs for the neglected tropical disease vaccines. Here, we review the current status of scientific and technical progress in the development of new neglected tropical disease vaccines, highlighting the successes that have been achieved (cysticercosis and echinococcosis) and identifying the challenges and opportunities for development of new vaccines for NTDs. Also highlighted are the contributions being made by non-profit product development partnerships that are working to overcome some of the economic challenges in vaccine manufacture, clinical testing, and global access.

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Figures

Fig. 1
Fig. 1. The geographic overlap of the Neglected Tropical Diseases (NTDs)
Of the 56 nations with five or more co-endemic NTDs, 40 are found in Africa, nine in Asia, five in the Americas, and two in the Middle East. Map prepared Molly Brady, Emory University and reproduced in Molyneux et al. (287).
Fig. 2
Fig. 2
Revised strategy for a human hookworm vaccine: a bivalent recombinant protein vaccine targeting blood feeding of Necator americnaus.
Fig. 3
Fig. 3. Immunoglobulin (Ig) A and immunity to amebiasis
Children with fecal IgA antibodies against the Gal/GalNAc lectin carbohydrate recognition domain (CRD) [IgA anti-CRD (+); n = 81] had a lower incidence of new intestinal Entamoeba histolytica infection compared with children lacking this response [IgA anti-CRD (−); n = 149]. The two groups are statistically significantly different (P ≤ 0.04) at every time point (from Haque et al. 219).
Fig. 4
Fig. 4. Leish-111f (L111f): a tandemly linked protein of three subunits
Each component of L111f, the first recombinant Leishmania vaccine candidate to enter clinical trials, was cloned from a Leishmania major expression library. LeIF, (ribosomal initiation factor identified by serological screening with human sera from healthy infected individuals); LmSTI1 (temperature inducible protein, identified by screening with sera from BALB/c mice infected with L. major); thiol-specific antioxidant (TSA, identified through screening with sera from BALB/c mice immunized with protective Leishmania antigens.
Fig. 5
Fig. 5. Induction of specific antibody following immunization of active cutaneous leishmaniasis patients
Immunoglobulin G antibody titers (per-protocol population). Black bar represents median vaccine versus adjuvant or placebo, day 84 P < 0.0001; day 168 P = 0.0019.
Fig. 6
Fig. 6. (A). Induction of specific cellular immune responses following immunization of active cutaneous leishmaniasis patients using Fluorescence Activated Cell Sorting (FACS)
FACS analysis of un-vaccinated mucosal leishmaniasis (ML) patient subject’s cells collected before (day 0) and after (day 84) three immunizations with Leish-111f (L111f) in MPL-SE which does not cure (chemotherapy only). Cells were analyzed following in vitro stimulation with vaccine antigen. (B). FACS analysis of ML patient subject’s cells collected before (day 0) and after (day 84) three immunizations with L111f in MPL-SE in combination with standard antimony therapy (immunochemotherapy). Cells were analyzed following in vitro stimulation with vaccine antigen.
Fig. 7
Fig. 7. Beneficial effects of vaccination of cutaneous leishmaniasis patients receiving antimony chemotherapy; decreased time to cure
All patients received antimony therapy plus three injections of saline (placebo), MPL-SE, 25 ug/dose (adjuvant), or vaccine (Leish-111f, 5–25 ug/dose in MPL-SE).

References

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