Toward a Defined Anti-Leishmania Vaccine Targeting Vector Antigens: Characterization of a Protective Salivary Protein
06 Aug 2001-Journal of Experimental Medicine (The Rockefeller University Press)-Vol. 194, Iss: 3, pp 331-342
TL;DR: Results indicate that DTH response against saliva provides most or all of the protective effects of this vaccine and that salivary gland proteins or their cDNAs are viable vaccine targets against leishmaniasis.
Abstract: Leishmania parasites are transmitted to their vertebrate hosts by infected phlebotomine sand fly bites. Sand fly saliva is known to enhance Leishmania infection, while immunity to the saliva protects against infection as determined by coinoculation of parasites with vector salivary gland homogenates (SGHs) or by infected sand fly bites (Kamhawi, S., Y. Belkaid, G. Modi, E. Rowton, and D. Sacks. 2000. Science. 290:1351–1354). We have now characterized nine salivary proteins of Phlebotomus papatasi, the vector of Leishmania major. One of these salivary proteins, extracted from SDS gels and having an apparent mol wt of 15 kD, was able to protect vaccinated mice challenged with parasites plus SGH. A DNA vaccine containing the cDNA for the predominant 15-kD protein (named SP15) provided this same protection. Protection lasted at least 3 mo after immunization. The vaccine produced both intense humoral and delayed-type hypersensitivity (DTH) reactions. B cell–deficient mice immunized with the SP15 plasmid vaccine successfully controlled Leishmania infection when injected with Leishmania plus SGH. These results indicate that DTH response against saliva provides most or all of the protective effects of this vaccine and that salivary gland proteins or their cDNAs are viable vaccine targets against leishmaniasis.
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TL;DR: Established models of T-helper-2-cell dominance in BALB/c mice infected with Leishmania major — involving the early production of interleukin-4 by a small subset of LeishMania-specific CD4+ T cells — have been refined by accumulating evidence that this response is not sufficient and, under some circumstances, not required to promote susceptibility.
Abstract: Established models of T-helper-2-cell dominance in BALB/c mice infected with Leishmania major -- involving the early production of interleukin-4 by a small subset of Leishmania-specific CD4+ T cells -- have been refined by accumulating evidence that this response is not sufficient and, under some circumstances, not required to promote susceptibility. In addition, more recent studies in L. major-resistant mice have revealed complexities in the mechanisms responsible for acquired immunity, which necessitate the redesign of vaccines against Leishmania and other pathogens that require sustained cell-mediated immune responses.
1,136 citations
TL;DR: This review addresses the problems insects and ticks face to feed on blood and the solutions these invertebrates engender to overcome these obstacles, including a sophisticated salivary cocktail of potent pharmacologic compounds.
Abstract: This review addresses the problems insects and ticks face to feed on blood and the solutions these invertebrates engender to overcome these obstacles, including a sophisticated salivary cocktail of potent pharmacologic compounds. Recent advances in transcriptome and proteome research allow an unprecedented insight into the complexity of these compounds, indicating that their molecular diversity as well as the diversity of their targets is still larger than previously thought.
686 citations
TL;DR: The current understanding of the mechanisms that Leishmania parasites use to ensure their transmission from sand fly vectors by bite is reviewed, and the most important mechanism is the creation of a “blocked fly” resulting from the secretion of promastigote secretory gel by the parasites in the anterior midgut.
462 citations
Cites background from "Toward a Defined Anti-Leishmania Va..."
...Another important area of future research is the possible development of anti-saliva vaccines (Kamhawi et al., 2000; Valenzuela et al., 2001; Oliveira et al., 2006)....
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...Another important area of future research is the possible development of anti-saliva vaccines (Kamhawi et al., 2000; Valenzuela et al., 2001; Oliveira et al., 2006)....
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TL;DR: The coevolution of sand flies with Leishmania species of mammals and lizards is considered in relation to the landscape epidemiology of leishmaniasis, a neglected tropical disease.
Abstract: Phlebotomines are the sole or principal vectors of Leishmania, Bartonella bacilliformis, and some arboviruses. The coevolution of sand flies with Leishmania species of mammals and lizards is considered in relation to the landscape epidemiology of leishmaniasis, a neglected tropical disease. Evolutionary hypotheses are unresolved, so a practical phlebotomine classification is proposed to aid biomedical information retrieval. The vectors of Leishmania are tabulated and new criteria for their incrimination are given. Research on fly-parasite-host interactions, fly saliva, and behavioral ecology is reviewed in relation to parasite manipulation of blood feeding, vaccine targets, and pheromones for lures. Much basic research is based on few transmission cycles, so generalizations should be made with caution. Integrated research and control programs have begun, but improved control of leishmaniasis and nuisance-biting requires greater emphasis on population genetics and transmission modeling. Most leishmaniasis transmission is zoonotic, affecting the poor and tourists in rural and natural areas, and therefore control should be compatible with environmental conservation.
426 citations
01 Jan 2007
TL;DR: In this article, the authors reviewed the mechanisms that Leishmania parasites use to ensure their transmission from sand fly vectors by bite and found that the most important mechanism is the creation of a "blocked fly" resulting from the secretion of promastigote secretory gel (PSG) by the parasites in the anterior midgut.
Abstract: A thorough understanding of the transmission mechanism of any infectious agent is crucial to implementing an effective intervention strategy. Here, our current understanding of the mechanisms that Leishmania parasites use to ensure their transmission from sand fly vectors by bite is reviewed. The most important mechanism is the creation of a ‘‘blocked fly’’ resulting from the secretion of promastigote secretory gel (PSG) by the parasites in the anterior midgut. This forces the sand fly to regurgitate PSG before it can bloodfeed, thereby depositing both PSG and infective metacyclic promastigotes in the skin of a mammalian host. Other possible factors in transmission are considered: damage to the stomodeal valve; occurrence of parasites in the salivary glands; and excretion of parasites from the anus of infected sand flies. Differences in the transmission mechanisms employed by parasites in the three subgenera, Leishmania, Viannia and Sauroleishmania are also addressed.
406 citations
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991 citations
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