Human anti‐saliva immune response following experimental exposure to the visceral leishmaniasis vector, Lutzomyia longipalpis

Abstract

Experiments in animals verified that phlebotomine saliva enhances Leishmania infection, and vaccination with saliva prevents disease. We have shown that individuals from an endemic area of visceral leishmaniasis displayed robust antibody responses to saliva from the vector Lutzomyia longipalpis, which correlated with anti-parasite cellmediated immunity. Here, we explored human anti-saliva responses following exposure to sand flies, using an in vivo bite model in which normal volunteers were exposed four times to 30 laboratory-reared Lu. longipalpis. Following the third exposure, normal volunteers developed diverse dermatological reactions at the site of insect bite. Serum from normal volunteers displayed high levels of anti-salivary gland sonicate IgG1, IgG4 and IgE as well as several salivary gland proteins. Furthermore, following in vitro stimulation with salivary gland sonicate, there was an increased frequency of CD4 + CD25 + and CD8 + CD25 + T cells as well as IFN-c and IL-10 synthesis. Strikingly, 1 year after the first exposure, PBMC from the volunteers displayed recall IFN-c responses that correlated with a significant reduction in infection rates using a macrophage-lymphocyte autologous culture. Together, these data suggest that human immunization against sand fly saliva is feasible and recall responses are obtained even 1 year after exposure, opening perspectives for vaccination in man.

Characterization of the Antibody Response to the Saliva of Phlebotomus papatasi in People Living in Endemic Areas of Cutaneous Leishmaniasis

“…It reported that individuals who were experimentally exposed to the bites of uninfected L. longipalpis developed anti-saliva antibodies restricted mostly to IgG1 and IgG4 subclasses. 22 Such results were close to those obtained in individuals exposed to the bites of Aedes . [23][24][25][26] In all these studies, the presence of IgG4 antibodies was correlated to the production of IgE antibodies suggesting that IgG4 was the result of an allergic reaction to mosquitoe bites.…”

Serological Responses and Biomarker Evaluation in Mice and Pigs Exposed to Tsetse Fly Bites

“…An advantage of this approach is that relatively simple serological tests could provide information on actual exposure to the bites of disease vectors and provide a risk indicator of contracting a vector-transmitted disease without the need of strenuous entomological surveys. Whole salivary gland extracts of sand flies [33], [34], [35], triatomine bugs [30], [31] and various mosquito species [36], [37], [38] can be used to assess biting exposure. It has been suggested that this type of serological approach would enable the detection of very low levels of exposure that could remain undetected by entomological trappings [39].…”

Epidemiological Study of the Association between Anti-Lutzomyia longipalpis Saliva Antibodies and Development of Delayed-Type Hypersensitivity to Leishmania Antigen

“…8,[10][11][12] On exposure to uninfected Lutzomyia longipalpis bites, normal human volunteers develop anti-sand fly saliva antibodies and cell-mediated immune response. 13 Host responses to antiLu. longipalpis saliva antibodies may be related to the development of delayed-type hypersensitivity to Leishmania antigen.…”