Study of the safety, immunogenicity and efficacy of attenuated and killed Leishmania (Leishmania) major vaccines in a rhesus monkey (Macaca mulatta) model of the human disease
V. F. Amaral,Antonio Teva,M. P. Oliveira-Neto,A. J. Silva,M. S. Pereira,Elisa Cupolillo,Renato Porrozzi,Sergio G. Coutinho,Claude Pirmez,Stephen M. Beverley,Gabriel Grimaldi +10 more
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TLDR
The most striking result was the lack of pathogenicity of the attenuated parasite, which persisted in infected animals for up to three months, but were incapable of causing disease under the conditions employed.Abstract:
We have compared the efficacy of two Leishmania (Leishmania) major vaccines, one genetically attenuated (DHFR-TS deficient organisms), the other inactivated [autoclaved promastigotes (ALM) with bacillus Calmete-Guerin (BCG)], in protecting rhesus macaques (Macaca mulatta) against infection with virulent L. (L.) major. Positive antigen-specific recall proliferative response was observed in vaccinees (79% in attenuated parasite-vaccinated monkeys, versus 75% in ALM-plus-BCG-vaccinated animals), although none of these animals exhibited either augmented in vitro gamma interferon (IFN-gamma) production or positive delayed-type hypersensitivity (DTH) response to the leishmanin skin test prior to the challenge. Following challenge, there were significant differences in blastogenic responses (p < 0.05) between attenuated-vaccinated monkeys and naive controls. In both vaccinated groups very low levels of antibody were found before challenge, which increased after infective challenge. Protective immunity did not follow vaccination, in that monkeys exhibited skin lesion at the site of challenge in all the groups. The most striking result was the lack of pathogenicity of the attenuated parasite, which persisted in infected animals for up to three months, but were incapable of causing disease under the conditions employed. We concluded that both vaccine protocols used in this study are safe in primates, but require further improvement for vaccine application.read more
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Visceral leishmaniasis: what are the needs for diagnosis, treatment and control?
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Leishmaniasis Vaccine: Where are We Today?
TL;DR: A thorough understanding of protective immune responses and generation and maintenance of the immunological memory, the most important and least-studied aspect of antiparasitic vaccine development, during Leishmania infection is needed.
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Intracellular replication-deficient Leishmania donovani induces long lasting protective immunity against visceral leishmaniasis.
Angamuthu Selvapandiyan,Ranadhir Dey,Susanne Nylén,Robert Duncan,David B. Sacks,Hira L. Nakhasi +5 more
TL;DR: Results indicate that LdCen1−/− can be a safe and effective vaccine candidate against VL as well as mucocutaneous leishmaniasis causing parasites.
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Vaccination with Phosphoglycan-Deficient Leishmania major Protects Highly Susceptible Mice from Virulent Challenge without Inducing a Strong Th1 Response
TL;DR: It is indicated that the immunity induced can be maintained in the absence of a strong Th1 response and reported on attenuated parasites that may be used to induce long-term protection against leishmaniasis.
References
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Leishmaniases of the New World: current concepts and implications for future research.
Gabriel Grimaldi,Robert B. Tesh +1 more
TL;DR: This article reviews current concepts of the clinical forms, immunology, pathology, laboratory diagnosis, and treatment of the disease as well as aspects of its epidemiology and control and makes recommendations for future research on the disease.
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The Logic of Visceral Leishmaniasis Control
TL;DR: Both killing vectors and reducing susceptibility (by whatever means) are more effective than killing dogs or treating them with drugs, and a dog vaccine is highly desirable in Europe, where vector control is less likely to be successful.
Journal ArticleDOI
Randomised vaccine trial of single dose of killed Leishmania major plus BCG against anthroponotic cutaneous leishmaniasis in Bam, Iran.
Iraj Sharifi,Alireza Fekri,Mohammad Reza Aflatoonian,Ali Khamesipour,Abolhassan Nadim,Mohammad-Reza Ahmadi Mousavi,Ali Momeni,Y Dowlati,Tore Godal,Fabio Zicker,Pete Smith,Farrokh Modabber +11 more
TL;DR: A single dose of ALM + BCG was safe and more immunogenic than BCG alone, as measured by leishmanin skin test, and the preferential protective effect in boys may have resulted from a greater booster effect produced by repeated exposure to infected sandflies.
Journal ArticleDOI
Vaccine requirements for sustained cellular immunity to an intracellular parasitic infection
TL;DR: It is demonstrated that vaccination with plasmid DNA encoding a specific leish manial antigen is more effective than leishmanial protein plus recombinant IL-12 in eliciting long-term immunity capable of controlling L. major infection.
Journal ArticleDOI
Development of a safe live Leishmania vaccine line by gene replacement.
TL;DR: Dhfr-ts- was incapable of causing disease in both susceptible and immunodeficient (nu/nu) BALB/c mice, and could be used as a platform for delivery of immunogens relevant to other diseases.