Leishmaniasis vaccine

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A parasitologist working on L. major in a biocontainment hood Leishmania culture in hood 2.jpg
A parasitologist working on L. major in a biocontainment hood

A Leishmaniasis vaccine is a vaccine which would prevent leishmaniasis. As of 2017, no vaccine for humans was available. [1] [2] Currently some effective leishmaniasis vaccines for dogs exist. [3]

Contents

The parasite which causes leishmaniasis is Leishmania , which is a Trypanosomatida. The disease spreads from sandflies. Animals such as dogs can be a vector for having the parasite, spreading it to sandflies, and from sandflies to humans. A vaccination strategy to control or eliminate Leishmaniasis might include developing a vaccine for humans and other vaccines for animals.

Scientists wish for a vaccine and there is vaccine research. [4] There is also consideration that public health practices can control or eliminate leishmaniasis without a vaccine. [4]

Leishmanization

People who recover from leishmaniasis gain immunity from reinfection. [5] "Leishmanization" is the practice of inoculation with live Leishmania to induce mild cutaneous leishmaniasis (CL) to prevent future dangerous infection. [5] [6] Some Bedouin and Kurdish cultures practiced leishmanization as traditional medicine. [7] [8] There are historic accounts and decades of medical research describing the efficacy of this. [7]

Traditional knowledge about leishmanization has informed the development of a leishmaniasis vaccine. [7]

Vaccine development

A 2015 paper claimed that the development and use of a vaccine would be the best way to eliminate leishmaniasis from South Asia. [9] Attempts to create a vaccine with live, inactivated or attenuated Leishmania have failed. [10] Attempts to create a peptide, DNA, or protein vaccine have shown efficacy in animal vaccine models but not effective in humans. [10] There are a series of challenges with explanations in molecular biology which explain the difficulty of vaccine development. [10]

Vaccine development is difficult because the parasites live in humans, sandflies, and other animals, so a vaccine in humans alone would not eliminate the protozoan in insects and animals. [11] There is a challenge in interpreting the data in animal models to apply to humans. [12] Another challenge is effectively transferring knowledge from laboratory settings to field practice. [12] There is also a basic lack of scientific understanding of how an antiparasitic vaccine should generate and maintain immunological memory during parasitic infection. [12]

The development of a vaccine using CRISPR-Cas9 technology was published in 2020 [13] which showed that inoculation with a live attenuated Leishmania major strain induces durable protection, analogous to leishmanization. Another gene deletion mutant was created in a Leishmania mexicana strain in 2022, showing complete inhibition of the typical cutaneous lesions in mouse models thanks to a diminished induction of the Th2 cytokines. [14]

Clinical trials

As of 2016 there are several vaccines in development and three have gone to clinical trials. [1] One clinical trial in Brazil used an inactivated vaccine for human immunotherapy. [1] Another in Uzbekistan used an attenuated vaccine for human immunotherapy. [1] Another in Brazil was vaccination of dogs to prevent those animals from spreading the disease. [1]

The dog vaccines are successful in providing immunity. [3] In 2008, a vaccine for dogs was launched in Brazil, which is known as LeishTech, a recombinant protein based vaccine. [15] In 2011 CaniLeish, a vaccine made with antigens from L. infantum, was licensed in Europe. [6] [15] Efforts are on ongoing to develop further vaccines for dogs with one second generation vaccine up for approval in Brazil as of 2017. [2]

History

Saul Adler domesticated the Syrian hamster in the 1930s to use in Leishmaniasis research. Saul Adler. Photograph by Werner Braun. Wellcome V0027916.jpg
Saul Adler domesticated the Syrian hamster in the 1930s to use in Leishmaniasis research.

In the early 1900s scientists learned how to culture the parasite, and work in the 1940s led by Saul Adler led to the practice of leishmanization being widespread in Israel and Russia until the 1980s, when large-scale clinical trials showed that the practice led to long-term skin lesions, exacerbation of psoriasis, and immunosuppression in some people. [7] [8] During the Iran–Iraq War over 2 million people in Iran were vaccinated this way. [17] [18] As of 2006 such vaccines were still licensed and used in Uzbekistan. [17]

Clinical trials with killed parasites had conflicting results in the 1940s, and work on such vaccines did not resume until the 1970s, when there were promising small clinical trials, and which continued with extensive clinical trials in Ecuador, Brazil, in Iran, through the 1990s. [19]

Preclinical work with genetically modified live attenuated parasite vaccines was conducted in the 1990s and 2000s, as did work with synthetic peptides, recombinant proteins, glycoproteins and glycolipids from leishmania species, and naked DNA. [19] [6] As of 2016, none of these second-generation vaccine candidates had reached the market, and few had been tested in clinical trials. [20]

Related Research Articles

<i>Leishmania</i> Genus of parasitic flagellate protist

Leishmania is a parasitic protozoan, a single-celled organism of the genus Leishmania that are responsible for the disease leishmaniasis. They are spread by sandflies of the genus Phlebotomus in the Old World, and of the genus Lutzomyia in the New World. At least 93 sandfly species are proven or probable vectors worldwide. Their primary hosts are vertebrates; Leishmania commonly infects hyraxes, canids, rodents, and humans.

<span class="mw-page-title-main">Leishmaniasis</span> Disease caused by parasites of the Leishmania type

Leishmaniasis is a wide array of clinical manifestations caused by parasites of the Trypanosomatida genus Leishmania. It is generally spread through the bite of phlebotomine sandflies, Phlebotomus and Lutzomyia, and occurs most frequently in the tropics and sub-tropics of Africa, Asia, the Americas, and southern Europe. The disease can present in three main ways: cutaneous, mucocutaneous, or visceral. The cutaneous form presents with skin ulcers, while the mucocutaneous form presents with ulcers of the skin, mouth, and nose. The visceral form starts with skin ulcers and later presents with fever, low red blood cell count, and enlarged spleen and liver.

<span class="mw-page-title-main">Sandfly</span> Name of several types of blood-sucking fly

Sandfly or sand fly is a colloquial name for any species or genus of flying, biting, blood-sucking dipteran (fly) encountered in sandy areas. In the United States, sandfly may refer to certain horse flies that are also known as "greenheads", or to members of the family Ceratopogonidae. The bites usually result in a small, intensely itchy bump or welt, the strength of which intensifies over a period of 5-7 days before dissipating. Moderate relief is achieved with varying success through the application of over the counter products such as Benadryl (ingested) or an analgesic cream such as After Bite. Outside the United States, sandfly may refer to members of the subfamily Phlebotominae within the Psychodidae. Biting midges (Ceratopogonidae) are sometimes called sandflies or no-see-ums. New Zealand sandflies are in the genus of sand fly Austrosimulium, a type of black fly.

<i>Lutzomyia</i> Genus of flies

Lutzomyia is a genus of phlebotomine sand flies consisting of nearly 400 species, at least 33 of which have medical importance as vectors of human disease. Species of the genus Lutzomyia are found only in the New World, distributed in southern areas of the Nearctic and throughout the Neotropical realm. Lutzomyia is one of the two genera of the subfamily Phlebotominae to transmit the Leishmania parasite, with the other being Phlebotomus, found only in the Old World. Lutzomyia sand flies also serve as vectors for the bacterial Carrion's disease and a number of arboviruses.

<i>Phlebotomus</i> Genus of flies

Phlebotomus is a genus of "sand flies" in the Diptera family Psychodidae. In the past, they have sometimes been considered to belong in a separate family, Phlebotomidae, but this alternative classification has not gained wide acceptance.

<span class="mw-page-title-main">Cutaneous leishmaniasis</span> Medical condition

Cutaneous leishmaniasis is the most common form of leishmaniasis affecting humans. It is a skin infection caused by a single-celled parasite that is transmitted by the bite of a phlebotomine sand fly. There are about thirty species of Leishmania that may cause cutaneous leishmaniasis.

<span class="mw-page-title-main">Visceral leishmaniasis</span> Human disease caused by protist parasites

Visceral leishmaniasis (VL), also known as kala-azar or "black fever", is the most severe form of leishmaniasis and, without proper diagnosis and treatment, is associated with high fatality. Leishmaniasis is a disease caused by protozoan parasites of the genus Leishmania.

<i>Leishmania infantum</i> Species of parasitic protist

Leishmania infantum is the causative agent of infantile visceral leishmaniasis in the Mediterranean region and in Latin America, where it has been called Leishmania chagasi. It is also an unusual cause of cutaneous leishmaniasis, which is normally caused by specific lineages. Wild canids and domestic dogs are the natural reservoir of this organism. The sandfly species Lutzomyia longipalpis serves as the primary vector for the transmission of the disease.

<i>Leishmania major</i> Species of parasitic protist

Leishmania major is a species of parasite found in the genus Leishmania, and is associated with the disease zoonotic cutaneous leishmaniasis. L. major is an intracellular pathogen which infects the macrophages and dendritic cells of the immune system. Though Leishmania species are found on every continent aside from Antarctica, Leishmania major is found only in the Eastern Hemisphere, specifically in Northern Africa, the Middle East, Northwestern China, and Northwestern India.

<span class="mw-page-title-main">Protozoan infection</span> Parasitic disease caused by a protozoan

Protozoan infections are parasitic diseases caused by organisms formerly classified in the kingdom Protozoa. They are usually contracted by either an insect vector or by contact with an infected substance or surface and include organisms that are now classified in the supergroups Excavata, Amoebozoa, SAR, and Archaeplastida.

<span class="mw-page-title-main">Canine leishmaniasis</span> Disease affecting dogs

Canine leishmaniasis (LEESH-ma-NIGH-ah-sis) is a zoonotic disease caused by Leishmania parasites transmitted by the bite of an infected phlebotomine sandfly. Canine leishmaniasis was first identified in Europe in 1903, and in 1940, 40% of all dogs in Rome were determined to be positive for leishmaniasis. Traditionally thought of as a disease only found near the Mediterranean basin, 2008 research claims new findings are evidence that canine leishmaniasis is currently expanding in continental climate areas of northwestern Italy, far from the recognized disease-endemic areas along the Mediterranean coasts. Cases of leishmaniasis began appearing in North America in 2000, and, as of 2008, Leishmania-positive foxhounds have been reported in 22 U.S. states and two Canadian provinces.

<i>Leishmania donovani</i> Species of intracellular parasite

Leishmania donovani is a species of intracellular parasites belonging to the genus Leishmania, a group of haemoflagellate kinetoplastids that cause the disease leishmaniasis. It is a human blood parasite responsible for visceral leishmaniasis or kala-azar, the most severe form of leishmaniasis. It infects the mononuclear phagocyte system including spleen, liver and bone marrow. Infection is transmitted by species of sandfly belonging to the genus Phlebotomus in Old World and Lutzomyia in New World. The species complex it represents is prevalent throughout tropical and temperate regions including Africa, China, India, Nepal, southern Europe, Russia and South America. The species complex is responsible for thousands of deaths every year and has spread to 88 countries, with 350 million people at constant risk of infection and 0.5 million new cases in a year.

<i>Leishmania tropica</i> Species of protozoan parasite

Leishmania tropica is a flagellate parasite and the cause of anthroponotic cutaneous leishmaniasis in humans. This parasite is restricted to Afro-Eurasia and is a common cause of infection in Afghanistan, Iran, Syria, Yemen, Algeria, Morocco, and northern India.

Leishmania braziliensis is a Leishmania species.

<i>Leishmania mexicana</i> Species of parasitic protist

Leishmania mexicana belongs to the Leishmania genus and is the causal agent of cutaneous leishmaniasis in Mexico and central America.

<i>Lutzomyia longipalpis</i> Species of fly

Lutzomyia longipalpis is a species complex of sandfly belonging to the family Psychodidae. This species is primarily present in Central and South America, but has also appeared in Mexico. There have been reports of L. longipalpis as far south as Argentina, as they are found in a wide variety of ecological conditions. Both males and females feed on sugars from plants and aphids, but only adult females feed on the blood of other mammals. The species has recently begun appearing in urban areas throughout Brazil, and serves as a key vessel for the propagation of the parasite Leishmania infantum. The presence of these flies appears to be strongly correlated to the presence of domestic chickens in Latin America. The first major urban outbreak of the lethal Visceral leishmanias epidemic was detected in Teresina, Piauí State in the early 1980s following a massive planting of acacias.

Kala azar in India refers to the special circumstances of the disease kala azar as it exists in India. Kala azar is a major health problem in India with an estimated 146,700 new cases per year as of 2012. In the disease a parasite causes sickness after migrating to internal organs such as the liver, spleen and bone marrow. If left untreated the disease almost always results in the death. Signs and symptoms include fever, weight loss, fatigue, anemia, and substantial swelling of the liver and spleen.

<span class="mw-page-title-main">Climate change and infectious diseases</span> Overview of the relationship between climate change and infectious diseases

Global climate change has resulted in a wide range of impacts on the spread of infectious diseases. Like other ways in which climate change affects on human health, climate change exacerbates existing inequalities and challenges in managing infectious disease. Infectious diseases whose transmission can be impacted by climate change include dengue fever, malaria, tick-borne diseases, leishmaniasis and Ebola virus disease. For example, climate change is altering the geographic range and seasonality of the mosquito that can carry dengue.

María Dora Feliciangeli was Professor of Medical Entomology at the University of Carabobo, Venezuela, who worked on the transmission of tropical parasites especially American trypanosomiasis and leishmaniasis. She was Coordinator of the National Reference Center of Sandflies and the Medical Entomology Section.

<i>Phlebotomus papatasi</i>

Phlebotomus papatasi is a species of insects commonly known as sandflies. Due to their ectothermic climate limitations, P. papatasi are confined to regions with temperatures above sixty degrees Fahrenheit for at least three months of the year, spanning over much of the European Mediterranean, North Africa, the Middle East, and Central Asia. Around one thousand sandfly species have been described, belonging to the subfamily Phlebotominae within the family Psychodidae. The Psychodidae family belongs to the order Diptera within the class Insecta of the subphylum Hexapoda of the Arthropod phylum.

References

  1. 1 2 3 4 5 Srivastava, S; Shankar, P; Mishra, J; Singh, S (12 May 2016). "Possibilities and challenges for developing a successful vaccine for leishmaniasis". Parasites & Vectors. 9 (1): 277. doi: 10.1186/s13071-016-1553-y . PMC   4866332 . PMID   27175732.
  2. 1 2 Ghorbani, M; Farhoudi, R (2018). "Leishmaniasis in humans: drug or vaccine therapy?". Drug Design, Development and Therapy. 12: 25–40. doi: 10.2147/DDDT.S146521 . PMC   5743117 . PMID   29317800.
  3. 1 2 Moafi, M; Rezvan, H; Sherkat, R; Taleban, R (2019). "Leishmania Vaccines Entered in Clinical Trials: A Review of Literature". International Journal of Preventive Medicine. 10: 95. doi: 10.4103/ijpvm.IJPVM_116_18 . PMC   6592111 . PMID   31360342.
  4. 1 2 Ghorbani, M; Farhoudi, R (2018). "Leishmaniasis in humans: drug or vaccine therapy?". Drug Design, Development and Therapy. 12: 25–40. doi: 10.2147/DDDT.S146521 . PMC   5743117 . PMID   29317800.
  5. 1 2 Mohebali, M; Nadim, A; Khamesipour, A (December 2019). "An overview of leishmanization experience: A successful control measure and a tool to evaluate candidate vaccines". Acta Tropica. 200: 105173. doi:10.1016/j.actatropica.2019.105173. PMID   31525323. S2CID   202641223.
  6. 1 2 3 Dunning, N. (17 February 2009). "Leishmania vaccines: from leishmanization to the era of DNA technology". Bioscience Horizons. 2 (1): 73–82. doi: 10.1093/biohorizons/hzp004 .
  7. 1 2 3 4 Handman, E. (1 April 2001). "Leishmaniasis: Current Status of Vaccine Development". Clinical Microbiology Reviews. 14 (2): 229–243. doi:10.1128/CMR.14.2.229-243.2001. PMC   88972 . PMID   11292637.
  8. 1 2 Palatnik-de-Sousa, CB (25 March 2008). "Vaccines for leishmaniasis in the fore coming 25 years". Vaccine. 26 (14): 1709–24. doi:10.1016/j.vaccine.2008.01.023. PMID   18295939.
  9. ↑ Engwerda, Christian R.; Matlashewski, G (July 2015). "Development of Leishmania vaccines in the era of visceral leishmaniasis elimination" (PDF). Transactions of the Royal Society of Tropical Medicine and Hygiene . 109 (7): 423–4. doi:10.1093/trstmh/trv039. PMID   26048873. Archived (PDF) from the original on 2020-03-22. Retrieved 2021-06-27.
  10. 1 2 3 Zutshi, Shubhranshu; Kumar, Sunil; Chauhan, Prashant; Bansode, Yashwant; Nair, Arathi; Roy, Somenath; Sarkar, Arup; Saha, Bhaskar (18 October 2019). "Anti-Leishmanial Vaccines: Assumptions, Approaches, and Annulments" (PDF). Vaccines. 7 (4): 156. doi: 10.3390/vaccines7040156 . PMC   6963565 . PMID   31635276. Archived (PDF) from the original on 2020-02-09. Retrieved 2021-06-27.
  11. ↑ Garg, Ravendra; Dube, Anuradha (March 2006). "Animal models for vaccine studies for visceral leishmaniasis" (PDF). Indian Journal of Medical Research . 123 (3): 439–54. PMID   16778322. Archived (PDF) from the original on 2021-06-28. Retrieved 2021-06-27.
  12. 1 2 3 Kedzierski, Lukasz (May 2010). "Leishmaniasis Vaccine: Where are We Today?". Journal of Global Infectious Diseases . 2 (2): 177–85. doi: 10.4103/0974-777X.62881 . PMC   2889658 . PMID   20606974.
  13. ↑ Zhang, Wen-Wei; Karmakar, Subir; Gannavaram, Sreenivas; Dey, Ranadhir; Lypaczewski, Patrick; Ismail, Nevien; Siddiqui, Abid; Simonyan, Vahan; Oliveira, Fabiano; Coutinho-Abreu, Iliano V.; DeSouza-Vieira, Thiago; Meneses, Claudio; Oristian, James; Serafim, Tiago D.; Musa, Abu; Nakamura, Risa; Saljoughian, Noushin; Volpedo, Greta; Satoskar, Monika; Satoskar, Sanika; Dagur, Pradeep K.; McCoy, J. Philip; Kamhawi, Shaden; Valenzuela, Jesus G.; Hamano, Shinjiro; Satoskar, Abhay R.; Matlashewski, Greg; Nakhasi, Hira L. (10 July 2020). "A second generation leishmanization vaccine with a markerless attenuated Leishmania major strain using CRISPR gene editing". Nature Communications. 11 (1): 3461. Bibcode:2020NatCo..11.3461Z. doi:10.1038/s41467-020-17154-z. PMC   7351751 . PMID   32651371. S2CID   218571920.
  14. ↑ Volpedo, Greta; Pacheco-Fernandez, Thalia; Holcomb, Erin A.; Zhang, Wen-Wei; Lypaczewski, Patrick; Cox, Blake; Fultz, Rebecca; Mishan, Chelsea; Verma, Chaitenya; Huston, Ryan H.; Wharton, Abigail R.; Dey, Ranadhir; Karmakar, Subir; Oghumu, Steve; Hamano, Shinjiro; Gannavaram, Sreenivas; Nakhasi, Hira L.; Matlashewski, Greg; Satoskar, Abhay R. (2 March 2022). "Centrin-deficient Leishmania mexicana confers protection against New World cutaneous leishmaniasis". npj Vaccines . 7 (1): 32. doi:10.1038/s41541-022-00449-1. PMC   8891280 . PMID   35236861.
  15. 1 2 Bowman, Dwight D. (2014). Georgis' Parasitology for Veterinarians (10th ed.). Elsevier Health Sciences. p. 440. ISBN   9781455739882. Archived from the original on 8 September 2017.
  16. ↑ Killick-Kendrick, R. (20 March 2013). "The race to discover the insect vector of kala-azar: a great saga of tropical medicine 1903–1942". Bulletin de la Société de pathologie exotique. 106 (2): 131–137. doi:10.1007/s13149-013-0285-x. PMID   23516011. S2CID   37040016.
  17. 1 2 Khamesipour, A; Rafati, S; Davoudi, N; Maboudi, F; Modabber, F (March 2006). "Leishmaniasis vaccine candidates for development: a global overview" (PDF). The Indian Journal of Medical Research. 123 (3): 423–38. PMID   16778321. Archived (PDF) from the original on 8 September 2017.
  18. ↑ Azizi MH, MH; et al. (2016). "History of Leishmaniasis in Iran from 19th Century Onward" (PDF). Arch Iran Med. 19 (2): 153–162. PMID   26838089. Archived (PDF) from the original on 16 January 2017.
  19. 1 2 Handman, E (April 2001). "Leishmaniasis: current status of vaccine development". Clinical Microbiology Reviews. 14 (2): 229–43. doi:10.1128/CMR.14.2.229-243.2001. PMC   88972 . PMID   11292637.
  20. ↑ Srivastava, S; Shankar, P; Mishra, J; Singh, S (12 May 2016). "Possibilities and challenges for developing a successful vaccine for leishmaniasis". Parasites & Vectors. 9 (1): 277. doi: 10.1186/s13071-016-1553-y . PMC   4866332 . PMID   27175732.
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