Although viruses and bacteria have been known as agents of diseases since 1546, 250 years went by until the first
vaccines against these pathogens were developed (1796 and 1800s). In contrast,
Malaria, which is a protozoan-
neglected disease, has been known since the 5th century BCE and, despite 2,500 years having passed since then, no human
vaccine has yet been licensed for
Malaria. Additionally, no modern human
vaccine is currently licensed against Visceral or
Cutaneous leishmaniasis. Vaccination against
Malaria evolved from the inoculation of irradiated sporozoites through the
bite of Anopheles mosquitoes in 1930's, which failed to give protection, to the use of controlled human
Malaria infection (
CHMI) provoked by live sporozoites of Plasmodium falciparum and curtailed with specific
chemotherapy since 1940's. Although the use of
CHMI for vaccination was relatively efficacious, it has some ethical limitations and was substituted by the use of injected
recombinant vaccines expressing the main
antigens of the parasite cycle, starting in 1980. Pre-erythrocytic (PEV), Blood stage (BSV), transmission-blocking (TBV), antitoxic (AT), and pregnancy-associated
Malaria vaccines are under development. Currently, the RTS,S-PEV
vaccine, based on the circumsporozoite
protein, is the only one that has arrived at the Phase III trial stage. The "R" stands for the central repeat region of Plasmodium (P.) falciparum circumsporozoite
protein (CSP); the "T" for the
T-cell epitopes of the CSP; and the "S" for
hepatitis B surface antigen (
HBsAg). In Africa, this latter
vaccine achieved only 36.7%
vaccine efficacy (VE) in 5-7 years old children and was associated with an increase in clinical cases in one assay. Therefore, in spite of 35 years of research, there is no currently licensed
vaccine against
Malaria. In contrast, more progress has been achieved regarding prevention of
leishmaniasis by
vaccine, which also started with the use of live
vaccines. For ethical reasons, these were substituted by second-generation subunit or
recombinant DNA and
protein vaccines. Currently, there is one live
vaccine for humans licensed in Uzbekistan, and four licensed veterinary
vaccines against
visceral leishmaniasis: Leishmune® (76-80% VE) and CaniLeish® (68.4% VE), which give protection against strong endpoints (severe disease and deaths under natural conditions), and, under less severe endpoints (parasitologically and PCR-positive cases), Leishtec® developed 71.4% VE in a low infective pressure area but only 35.7% VE and transient protection in a high infective pressure area, while Letifend® promoted 72% VE. A human
recombinant vaccine based on the
Nucleoside hydrolase NH36 of Leishmania (L.) donovani, the main
antigen of the Leishmune®
vaccine, and the
sterol 24-c-methyltransferase (SMT) from L. (L.) infantum has reached the Phase I clinical trial phase but has not yet been licensed against the disease. This review describes the history of
vaccine development and is focused on licensed formulations that have been used in preventive medicine. Special attention has been given to the delay in the development and licensing of human
vaccines against
Protozoan infections, which show high incidence worldwide and still remain severe threats to Public Health.