**5.2 Specific prevention**

To date, there is no immunization option available to prevent or treat any fungal infection. Although there have been numerous attempts to develop a potential vaccine against histoplasmosis, these candidates have only been tested on murine models. Various strategies have been used in the search for an effective vaccine for histoplasmosis. The active immunization approaches used in the research consisted of administration of recombinant heat shock protein rHsp60 or only the small protein fragment F3 of rHsp60, the surface protein H antigen, or auto-transplantation into a murine model of dendritic cells, primed *in vitro*, with apoptotic macrophages obtained by phagocytizing *H. capsulatum* yeast, inactivated by heat.

Research studies based on passive immunization methods have focused on the administration of monoclonal antibodies (mAbs Ig.M against histone 2B, mAbs Ig.G against rHsp60) or therapeutic pan-anti-fungal antibodies.

Immune system modulation strategies targeting the programmed cell death receptor-1 (PD-1) and its ligand (PD-L) have suggested that selective blockade of the PD-1/PD-L pathway may play a key therapeutic role in fungal immunity, not only for histoplasmosis but also for other mycoses [142].

The latest research in this field, approaching revolutionary methods of reverse vaccinology, comparative genomics, and molecular docking, have identified some candidate targets to produce both vaccines and new drugs against *H. capsulatum*. The most promising candidate vaccine target appears to be beta-1,3-glucanosyl transferase, the enzyme involved in the elongation of beta-(1-3)-glucans in the fungal cell wall, but further *in vivo* research is needed to test its efficacy and safety [143].

Recently, the WHO has released the fungal priority pathogen list (FPPL) to strengthen the global response against fungal infections. The FPPL highlights the need for actions, interventions, and strategies that focus on three main areas: surveillance, research and development, and public health actions [40].
