Immunity to a salivary protein of a sand fly vector protects against the fatal outcome of visceral leishmaniasis in a hamster model

Gomes, Régis; Teixeira, Clarissa; Teixeira, Maria Jânia; Oliveira, Fabiano; Menezes, Marcelo Bezerra de; Silva, Claire; Oliveira, Camila I. de; Miranda, José Carlos; Elnaiem, Dia-Eldin A.; Kamhawi, Shaden; Valenzuela, Jesús G.; Brodskyn, Cláudia

doi:10.1073/pnas.0712153105

Cited by 208 publications

(260 citation statements)

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“…17 Thus, proper selection of a vector-based vaccine candidate is of major importance. 17,18 Laboratory colonies of insects are often accepted as being representative of field populations from which they have been derived, but this assumption may be challenged because colonies frequently incorporate only a fraction of the genetic variability present in the original populations. 19 It has been reported that laboratory colonization of sand flies reduces natural genetic variability, and might foster selection for certain traits that are normally suppressed in field populations.…”

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confidence: 99%

Lack of Protection of Pre-Immunization with Saliva of Long-Term Colonized Phlebotomus papatasi against Experimental Challenge with Leishmania major and Saliva of Wild-Caught P. papatasi

Ahmed¹,

Kaabi²,

Chelbi³

et al. 2010

The American Journal of Tropical Medicine and Hygiene

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Several studies have shown that pre-immunization of mice with needle-injected saliva or pre-exposure to uninfected bites of Phlebotomus papatasi provided protection against infection with Leishmania major , the etiologic agent of zoonotic cutaneous leishmaniasis (ZCL).1-3 These studies were performed by using long-term laboratory colonized sand flies mainly because of the difficulty of working with wild-caught flies. A puzzling fact is that people in leishmaniasis-endemic areas succumb of ZCL despite the high frequency of uninfected bites compared with infected ones. 4 We showed in a previous study that pre-immunization of mice with salivary gland homogenate (SGH) of wild-caught P. papatasi does not confer protection against L. major co-inoculated with the same type of SGH compared with a significant protection obtained when pre-immunization and challenge were performed with SGH of long-term colonized flies. 5 It was reported that colonized and wild-caught Lutzomyia longipalpis differ in the composition and the amount of salivary proteins and these differences may account for the lower effect observed on the modulation of experimental Leishmania infection by wild-caught SGH. 6,7 Thus, these studies provide good evidence that the outcome of Leishmania infection differs significantly between colonized and wild-caught salivary gland proteins. Our aim in this study was to assess the protective effect of pre-immunization with SGH of long-term colonized P. papatasi on experimental L. major challenge co-inoculated with SGH of wild-caught P. papatasi .Phlebotomus papatasi (Tunisian strain that originated in the Governorate of Sidi Bouzid) have been reared at the Vector Ecology Laboratory of the Institut Pasteur de Tunis since 2003. 8 This colony is maintained without being supplemented periodically with wild-caught P. papatasi . Generation F 39 was used in this study. Wild sand flies were collected using CDC light traps from animal shelters located in the village of Felta (Governorate of Sidi Bouzid), a focus highly endemic for ZCL.9 Preparation of SGH from laboratory-reared and wild-caught P. papatasi was performed as described. 5 A highly virulent strain of L. major , MHOM/TN/95/GLC94, isolated from a patient in Tunisia was used in this study. 5 We used female BALB/c mice (6-8 weeks of age) bred in the animal facility of the Institut Pasteur de Tunis.Mice were immunized intradermally in the right ear with the equivalent of two pairs of salivary glands in 10 µL of phosphate-buffered saline (PBS). Two groups of 10 mice each were pre-immunized with SGH of long-term colonized female P. papatasi (F 39 ), once a week for two weeks. In the fourth week, the first [CSGH (F 39 )-L.m+CSGH (F 39 )] and the second [CSGH (F 39 )-L.m+WSGH] groups were challenged with 10 6 stationary phase L. major promastigotes in 50 µL of PBS co-inoculated subcutaneously in the right hind footpads with SGH of long-term, colonized and SGH of wild-caught, female P. papatasi , respectively. Three control groups of 10 mice each were used in this stud...

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confidence: 99%

Lack of Protection of Pre-Immunization with Saliva of Long-Term Colonized Phlebotomus papatasi against Experimental Challenge with Leishmania major and Saliva of Wild-Caught P. papatasi

Ahmed¹,

Kaabi²,

Chelbi³

et al. 2010

The American Journal of Tropical Medicine and Hygiene

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“…The protection provided by PpSP15 against Leishmania has been confirmed in mice and this protective immune response has not been observed in Rhesus monkeys [83]. Therefore, in different vertebrate hosts, different molecules of the saliva are responsible to provide protection against Leishmania infection [81,70]. So far, no salivary molecule from P. papatasi has been identified to confer protection in humans [83].…”

Section: New Approaches To the Vaccine Developmentmentioning

confidence: 96%

“…Following immunization of a hamster model of VL with LJM19 salivary protein from Lu. longipalpis, the parasite burden was shown to be decreased in the liver for 5 months after the infection and a strong DTH response with IFN-γ production was induced, 48 hours after the exposure to the sand fly bites [81].…”

Section: Sand Fly Saliva and Induction Of Immune Responses And Protecmentioning

confidence: 99%

Sand fly saliva: toward a vaccine against leishmaniases

Vasoukolaei¹

2015

vacres

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Leishmaniases are a group of sand fly-borne diseases caused by protozoan parasites from species of Leishmania genus. These diseases are reported in about 100 countries with a prevalence of 12 million people infected and incidence of 2 million people per year, putting approximately 350 million people at risk of the infections. Leishmaniases are endemic and are considered as important public health problems in many provinces of Iran. The infection is transmitted through the bite of phlebotomine sand flies. The sand fly salivates while biting the vertebrate host. The saliva of phlebotomines consists of different molecules that are necessary for a sand fly to successfully take a blood meal. Additionally, previous exposures to sand fly saliva indirectly affect the establishment of Leishmania in the vertebrate host. Moreover, mice previously exposed to the saliva by injection or by uninfected sand fly bites have shown both humoral and cellular immune responses against the salivary antigens that protects them against Leishmania infection. Importantly, the immunization of mice with defined molecules from the saliva of the vector species has also conferred a strong protection against Leishmania infection. This suggests that such salivary components may be considered as candidates for a cocktail vaccine against leishmaniases. The current article briefly explains the potential of salivary components of sand fly vectors as immunological items to prevent leishmaniasis. So far, there is no efficient vaccine against these infections and efforts are required to be focused on developing effective and applicable vaccines against leishmaniases.

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“…In this context, PdSP15, a 15-kDa salivary protein, which is a member of the family of small odorant binding proteins from Phlebotomus duboscqi, was evaluated as a candidate antigen against leishmaniasis in non-human primates (64) . In addition, LJM19, an 11-kDa salivary protein of unknown function and LJL143, a 38-kDa salivary protein with anticoagulant activity (65) , both of which are present in the saliva of Lutzomyia longipalpis, were shown to be protective against VL (66) . Table 1 shows a summary of relevant vaccine candidates evaluated as individual recombinant protein or polyprotein vaccines against VL (67) (79) .…”

Section: Second-generation Vaccines Against Visceral Leishmaniasismentioning

confidence: 99%

Recent updates and perspectives on approaches for the development of vaccines against visceral leishmaniasis

Duarte

Lage

Martins

et al. 2016

Rev. Soc. Bras. Med. Trop.

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Visceral leishmaniasis (VL) is one of the most important tropical diseases worldwide. Although chemotherapy has been widely used to treat this disease, problems related to the development of parasite resistance and side effects associated with the compounds used have been noted. Hence, alternative approaches for VL control are desirable. Some methods, such as vector control and culling of infected dogs, are insuffi ciently effective, with the latter not ethically recommended. The development of vaccines to prevent VL is a feasible and desirable measure for disease control; for example, some vaccines designed to protect dogs against VL have recently been brought to market. These vaccines are based on the combination of parasite fractions or recombinant proteins with adjuvants that are able to induce cellular immune responses; however, their partial effi cacy and the absence of a vaccine to protect against human leishmaniasis underline the need for characterization of new vaccine candidates. This review presents recent advances in control measures for VL based on vaccine development, describing extensively studied antigens, as well as new antigenic proteins recently identifi ed using immuno-proteomic techniques.

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Immunity to a salivary protein of a sand fly vector protects against the fatal outcome of visceral leishmaniasis in a hamster model

Cited by 208 publications

References 43 publications

Lack of Protection of Pre-Immunization with Saliva of Long-Term Colonized Phlebotomus papatasi against Experimental Challenge with Leishmania major and Saliva of Wild-Caught P. papatasi

Lack of Protection of Pre-Immunization with Saliva of Long-Term Colonized Phlebotomus papatasi against Experimental Challenge with Leishmania major and Saliva of Wild-Caught P. papatasi

Sand fly saliva: toward a vaccine against leishmaniases

Recent updates and perspectives on approaches for the development of vaccines against visceral leishmaniasis

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