# An Overview of the Factors Related to Leishmania Vaccine Development

## TL;DR

This paper reviews the challenges in developing a Leishmania vaccine, focusing on immune responses, host factors, and limitations of animal models.

## Contribution

The paper provides a comprehensive overview of factors affecting Leishmania vaccine development, highlighting gaps in current research.

## Key findings

- Animal models like BALB/c mice use higher parasite loads than natural human infections, potentially skewing vaccine efficacy results.
- Despite 20 years of research, vaccines show only partial protection, regardless of adjuvants or host species.
- Non-protective Th2 or regulatory T cell responses hinder effective vaccine development.

## Abstract

Leishmaniasis is an infectious disease caused by several species of Leishmania parasites that preferentially infect macrophages as host cells. These intracellular parasites can evade the main microbicidal effector mechanisms of phagocytic cells and, in turn, are able to stimulate marked Th2 or regulatory T cell immune responses, which are not protective for the host. The presence of a non-protective immune response, together with the multiplication and spread of Leishmania parasites throughout the tissues, leads to the main clinical forms of leishmaniasis, such as cutaneous and visceral leishmaniasis. Although some clinical forms can be reproduced in experimental hosts such as mice and hamsters, these models do not fully mimic natural infection, which, in fact, impacts experimental vaccine development. For example, BALB/c mice are generally infected with around one million parasites, whereas humans are not infected with more than 1000 parasites, together with vector saliva. This excessive number of parasites in experimental models may affect the efficacy of vaccines in preclinical studies. Indeed, many experimental studies conducted over the past 20 years have shown only partial protection, regardless of the vaccine generation, host species employed, or the use of adjuvants. This review aims to summarize the main aspects associated with Leishmania vaccine development, including parasite diversity, host factors, immune responses, adjuvants, and antigens. Although many elegant studies have been conducted, it is possible that some essential step is still missing for the development of an effective vaccine for human use.