Leishmania vaccines entered in clinical trials: A review of literature

Abstract

Leishmaniasis is considered as a zoonotic infection and neglected tropical disease. Leishmania treatment is not totally successful and imposes high expenditures, especially in developing countries. Since the natural infection leads to the robust immunity in most of the human cases, many bodies of research have been focusing on Leishmania vaccines, being capable to control Leishmania infection. First generation vaccines (such as Leishmune ® and CaniLeish ® ) have proved robust protective immunity in dogs. In human, recombinant vaccines, including Leish-F1 could confer some degrees of protective immunity against natural infection. Recently, ChAd63-KH DNA vaccine has been accomplished in providing prevention against Leishmania infection; however, this vaccine should be further evaluated in other clinical trials.

The Delay in the Licensing of Protozoal Vaccines: A Comparative History

“…As discussed before, dead parasites with or without adjuvants composed the first generation of vaccines against leishmaniasis. These were mainly directed toward preventing the infections caused by the agents of CL (3,78,80,81). Later, secondgeneration vaccines were developed, which included in their formulation either genetically modified live Leishmania or Leishmania genes expressed by viruses or recombinant, synthetic, or partially purified native antigen subunits.…”

“…Finally, the thirdgeneration vaccines are composed of parasite antigens cloned in eukaryotic promoter vectors injected into the host muscle (3,4,80). Detailed reviews have previously summarized the vaccine antigens under research and those that were already tested in Phase II and Phase III trials (80)(81)(82), as well as the most suitable adjuvants (82). In this chapter, we will focus our review on the licensed vaccines against Leishmania.…”

“…Regarding the veterinary vaccines against ZVL, two preventive canine formulations have been registered in Brazil: Leishmune R in 2003 (80)(81)(82)(83)(84) and Leishtec R in 2008 (85). In Europe, where visceral leishmaniasis is also a canid zoonosis, two other vaccines were licensed: Canileish R in 2011 (86) and Letifend R (87) in 2016.…”

Role of Host and Parasite MIF Cytokines during Leishmania Infection

“…Additionally, the prospect of targeting Leishmania MIF for vaccination is promising. Immunization with parasite antigens has proved successful in commercially available vaccines for canines including Leishmune®and Canileish®, however similar approaches have been less promising in humans, and thus a more sophisticated strategy to promote immunity may be necessary [129]. Because Leishmania MIF appears to play a role in reducing long-term immunity, immunization with the cytokine could prove a successful strategy for inducing protection to initial and recurrent infection.…”

Protective or Detrimental? Understanding the Role of Host Immunity in Leishmaniasis

“…The inoculation of live and virulent Leishmania parasites termed leishmanization was a common vaccination strategy in endemic areas that conferred protection to natural and exacerbated Leishmania infections induced by sandfly transmission, but this practice was largely discontinued due to safety and reproducibility issues [154]. Attempts to emulate the anti-Leishmania responses acquired by "leishmanized" individuals with whole-killed or attenuated parasite-based formulations have raised concerns regarding the low immunogenicity and the potential reversion to a more virulent phenotype, respectively, in addition to variations in vaccine efficacy observed in clinical trials in different areas [153][154][155]. Yet, the use of adjuvants to tailor immune responses through activation of specific innate pathogen-recognition receptors (PRRs), such as TLRs, has been shown to enhance the generation of Th1 memory cells and parasite-specific responses to secondary challenges [156].…”