Overcoming roadblocks in the development of vaccines for leishmaniasis

Abstract

Introduction The leishmaniases represent a group of parasitic diseases caused by infection with one of several species of Leishmania parasites. Disease presentation varies because of differences in parasite and host genetics and may be influenced by additional factors such as host nutritional status or co-infection. Studies in experimental models of Leishmania infection, vaccination of companion animals and human epidemiological data suggest that many forms of leishmaniasis could be prevented by vaccination, but no vaccines are currently available for human use. Areas covered We describe some of the existing roadblocks to the development and implementation of an effective leishmaniasis vaccine, based on a review of recent literature found on PubMed, BioRxiv and MedRxiv. In addition to discussing scientific unknowns that hinder vaccine candidate identification and selection, we explore gaps in knowledge regarding the commercial and public health value propositions underpinning vaccine development and provide a route map for future research and advocacy. Expert opinion Despite significant progress, leishmaniasis vaccine development remains hindered by significant gaps in understanding that span the vaccine development pipeline. Increased coordination and adoption of a more holistic view to vaccine development will be required to ensure more rapid progress in the years ahead.

Anti-trypanosomatid drug discovery: progress and challenges

“…Although there are knowledge gaps that must be addressed before effective Leishmania spp. vaccines are provided for humans or for companion animals, there have been notable examples of recent progress in this area 107 . Prophylactic vaccines, therapeutic vaccines and vaccines for use in combination with host-directed immunochemotherapy are all under active development.…”

Leishmaniasis Vaccines: Applications of RNA Technology and Targeted Clinical Trial Designs

“…Unfortunately, despite the plethora of preclinical evaluations multiple factors have precluded advancement of more than a few Leishmania targeting vaccines to clinical trial. The sheer volume of potential vaccine platforms and antigen targets identified, the substantial economic impact of producing these as GMP-grade, and the lack of availability of safe and effective adjuvants with which to enhance or sustain responses, has led to reticence in advancing to trial candidates that appear to have 'room for improvement' [12][13][14][15]. Further, given that infection is reliant on sand fly vector transmission and sand fly populations are impacted by seasonal variation and micro-geography, pre-planning for enactment in regions with sufficiently high parasite transmission at time of trial is both difficult and unassured.…”

Constituents of the Stem Bark of Symphonia globulifera Linn. f. with Antileishmanial and Antibacterial Activities

“…Visceral leishmaniasis remains the most lethal if left untreated, with the most severe and underreported form of the disease representing up to 95% of cases [ 3 , 4 , 5 , 6 ]. Based on the most recent available data on this disease, between 498,000 and 862,000 new cases of all forms of leishmaniasis occur annually, resulting in up to 18,700 deaths and approximately 1.6 million disability-adjusted life years lost [ 7 ]. Moreover, the number of imported infection cases in non-endemic areas is increasing [ 8 , 9 , 10 ].…”