From infection to vaccination: reviewing the global burden, history of vaccine development, and recurring challenges in global leishmaniasis protection

Abstract

Introduction: Leishmaniasis is a major public health problem and the second most lethal parasitic disease in the world due to the lack of effective treatments and vaccines. Even when not lethal, leishmaniasis significantly affects individuals and communities through life-long disabilities, psychosociological trauma, poverty, and gender disparity in treatment.Areas covered: This review discusses the most relevant and recent research available on Pubmed and GoogleScholar highlighting leishmaniasis' global impact, pathogenesis, treatment options, and lack of effective control strategies. An effective vaccine is necessary to prevent morbidity and mortality, lower health care costs, and reduce the economic burden of leishmaniasis for endemic low-and middle-income countries. Since there are several forms of leishmaniasis, a pan-Leishmania vaccine without geographical restrictions is needed. This review also focuses on recent advances and common challenges in developing prophylactic strategies against leishmaniasis. Expert opinion: Despite advances in pre-clinical vaccine research, approval of a human leishmaniasis vaccine still faces major challenges -including manufacturing of candidate vaccines under Good Manufacturing Practices, developing well-designed clinical trials suitable in endemic countries, and defined correlates of protection. In addition, there is a need to explore Challenge Human Infection Model to avoid large trials because of fluctuating incidence and prevalence of leishmanasis.

Assembly of a Large Collection of Maxicircle Sequences and Their Usefulness for Leishmania Taxonomy and Strain Typing

“…Leishmaniasis is a major public health problem and the second most lethal parasitic disease, after malaria. In 2016, WHO reported that more than one billion people lived in Leishmania endemic regions and that every year 1 million CL, 300,000 VL, and 20–50,000 lethal VL cases occur [ 2 ] (and references therein).…”

Host–Pathogen Interaction in Leishmaniasis: Immune Response and Vaccination Strategies

“…Several gene targets have been selected for defined attenuated Leishmania vaccines, such as dhfr, lpg2, cpa, cpb, Ufm1, p27, SIR2, BT1, HSP70, centrin, and the paraflagellar rod-2 locus [227,[230][231][232]. However, genetically modified vaccines showed varying degree of stability and protection in animal models [227,233]. L. major dihydrofolate reductase-thymidylate synthase (DHFR-TS) gene knock-out was the first to be tested against virulent L. amazonensis and L. major infections as a potential vaccine [234,235] in susceptible and resistant murine models, but failed to confer protective immunity in rhesus monkey [236].…”

Overcoming roadblocks in the development of vaccines for leishmaniasis

“…The recent application of CRISPR-cas9 technology in Leishmania provides opportunities to introduce gene modifications/deletions creating parasite strains lacking specific antigens, a valuable tool to assess the importance of putative virulence factors and to formally distinguish between bystander and antigen-specific immunity following vaccination. In addition, CRISPR-cas9 underpins the development of live GA Leishmania vaccines [ 33 ].…”

“…A new generation of live genetically attenuated (GA) vaccines for leishmaniasis have now been developed, showing great promise in experimental models [ 31 ], including cross protection by a L. major centrin −/− vaccine against vector-transmitted L. donovani infection in hamsters [ 32 ]. These are discussed more fully elsewhere [ 33 ]. Second-generation subunit vaccines (including peptides and proteins in a variety of adjuvant and delivery systems [ 34 ];) have shown promise in various experimental models of cutaneous and visceral leishmaniasis.…”