Electrophoretic Analysis of Kala-azar Human Serum. Hypergammaglobulinemia Associated with Seronegative Reactions for Syphilis.

Cooper, Gerald R.; Rein, Charles R.; Beard, J. W.

doi:10.3181/00379727-61-15265

Cited by 27 publications

(6 citation statements)

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“…The role of anti-leishmanial antibody response seen in VL is unclear. Hypergammaglobulinemia has long been recognized as a detrimental factor in VL, since higher antibody levels correlate positively with disease severity and decreases after cure ( 31 – 33 ). It was also demonstrated that most of the circulating IgGs are not parasite-specific, as a result of polyclonal B cell activation ( 34 , 35 ).…”

Section: Discussionmentioning

confidence: 99%

Leishmania infantum Virulence Factor A2 Protein: Linear B-Cell Epitope Mapping and Identification of Three Main Linear B-Cell Epitopes in Vaccinated and Naturally Infected Dogs

et al. 2018

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In Brazil, canine visceral leishmaniasis (CVL) is caused by Leishmania infantum, presenting a broad spectrum of clinical manifestations. Dogs are the main parasite reservoir in urban areas and canine cases precede human infection. Currently, A2 protein based Leish-Tec® vaccine is the only vaccine commercially available against CVL in Brazil. Considering that the main screening and confirmatory tests of canine infection are serological, it is possible that the antibody response elicited after vaccination interfere with diagnosis, leading to the inability to distinguish between vaccinated and infected animals. In order to identify the specific B-cell response induced after vaccination, A2 protein sequence was screened for main linear B-cell epitopes using in silico prediction (Bepipred) and immunological confirmation by ELISA. Three amino acid sequences were described as potential B-cell epitopes (SV11-SAEPHKAAVDV, PP16-PQSVGPLSVGPQSVGP, and VQ34-VGPLSVGPQSVGPLSVGPLSVGPQAVGPLSVGPQ). Specific IgG ELISAs were performed in sera of 12 immunized dogs living in non-endemic areas, followed for up to 1 year after immunization. The results were compared with those obtained in a group of 10 symptomatic and 10 asymptomatic CVL dogs. All predicted epitopes were confirmed as linear B-cell epitopes broadly recognized by sera from studied dogs. Total IgG ELISAs demonstrated distinct patterns of response between peptides in the immunized and CVL groups. VQ34 peptide was recognized by the majority of sera from vaccinated and symptomatic dogs, and increases after vaccination. PP16 induced low levels of specific IgG that increased 1 year after immunization. Interestingly, a low frequency of reactivity was found against SV11 in naturally infected dogs (symptomatic and asymptomatic), while 83.3% of vaccinated dogs presented positive responses 1 year after immunization. The two animals in the vaccinated group that did not respond to SV11 1 year after immunization presented positive serology both 30 days and 6 months after immunization. In summary, we identified three main linear B-cell epitopes in A2 based vaccine. Moreover, the humoral response against SV11 presented marked differences between infected and Leish-Tec vaccinated dogs, and should be further investigated, in large trials, to confirm its potential as a serological marker able to distinguish between infected and vaccinated dogs.

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Section: Discussionmentioning

confidence: 99%

Leishmania infantum Virulence Factor A2 Protein: Linear B-Cell Epitope Mapping and Identification of Three Main Linear B-Cell Epitopes in Vaccinated and Naturally Infected Dogs

et al. 2018

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“…In visceral leishmaniasis, the level of total immunoglobulins is markedly elevated (10,11). Specific antibodies are also present.…”

Section: Discussionmentioning

confidence: 99%

Antiactin and antitubulin antibodies in canine visceral leishmaniasis

Patéraki¹,

Portocala²,

Labrousse³

et al. 1983

Infect Immun

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Visceral leishmaniasis, a chronic and often fatal disease, is caused by the protozoan parasite Leishmania donovani. Both specific and nonspecific antibodies are produced in the course of the disease, and autoantibodies may be involved in pathogenesis. Tubulin and actin have been found to be associated with L. donovani. To learn whether antiactin and antitubulin antibodies are present in visceral leishmaniasis, we tested sera from 263 infected dogs by enzyme-linked immunosorbent assay for antibodies to the antigens L. donovani, actin, and tubulin. All samples reacted positively with L. donovani, and a high percentage reacted positively with all three antigens. Sera from 202 uninfected dogs were also tested, none reacted with L. donovani antigen, although positive reactions were observed for 8 of the samples with actin or tubulin. It was found that the antibodyantigen reaction occurred at the Fab portion of the immunoglobulin molecule. Competitive enzyme immunoassays showed that the reaction was inhibited if the positive serum was first incubated with L. donovani antigen, actin, or tubulin and then tested by enzyme-linked immunosorbent assay. These results suggest that antiactin and antitubulin antibodies are present in the sera of dogs infected with visceral leishmaniasis.

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“…Additionally, it has been shown that antibody-opsonized parasites are more efficiently taken by phagocytes that will become "permissive hosts" due to the high IL-10 and low IL-12 secretion phenotype induced by antibody Fc-receptor (FcγR) interactions [144][145][146][147]. Importantly, one of the hallmarks of human disease, is hypergammaglobulinemia (that correlates with disease severity), resultant from a polyclonal B-cell activation, being consequently most of the circulating antibodies non-parasite specific [148][149][150]. Still, and because the development and role of humoral responses in leishmaniasis is controversial and not completely understood, they may be important [151,152].…”

Section: From "Mice To Man": the Issue Of Animal Models Correlates Omentioning

confidence: 99%

Vaccines for Human Leishmaniasis: Where Do We Stand and What Is Still Missing?

Cecílio¹,

Oliveira²,

Cordeiro-da-Silva³

2018

Leishmaniases as Re-Emerging Diseases

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Responsible for up to 30,000 deaths annually, leishmaniasis is a complex spectrum of diseases endemic in 97 countries around the globe. Disease control relies heavily on the early diagnosis and treatment of the active cases (relevant for anthroponotic disease), although it is widely accepted that a prophylactic vaccine for human leishmaniasis is the way to achieve the successful elimination of human disease (taking in consideration the vast list of non-human reservoirs that enable the perpetuation of parasites all around the globe). The notion that infection leads to strong and long-lasting immunity against leishmaniasis supports vaccination as an achievable goal. However, and in spite of the different candidates tested along the years, till date, we still do not have an approved vaccine for humans. In this chapter, we will explore the last advances made in the field of vaccines against Leishmania without forgetting the historical perspective, essential to the understanding of the road already undergone. We will then discuss the correlates of disease and protection, still neither consensual nor definitive, as well as the issue of pre-clinical to clinical translation. The complete understanding of these issues will be essential for the approval of a successful vaccine for human leishmaniasis.

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Electrophoretic Analysis of Kala-azar Human Serum. Hypergammaglobulinemia Associated with Seronegative Reactions for Syphilis.

Cited by 27 publications

References 0 publications

Leishmania infantum Virulence Factor A2 Protein: Linear B-Cell Epitope Mapping and Identification of Three Main Linear B-Cell Epitopes in Vaccinated and Naturally Infected Dogs

Leishmania infantum Virulence Factor A2 Protein: Linear B-Cell Epitope Mapping and Identification of Three Main Linear B-Cell Epitopes in Vaccinated and Naturally Infected Dogs

Antiactin and antitubulin antibodies in canine visceral leishmaniasis

Vaccines for Human Leishmaniasis: Where Do We Stand and What Is Still Missing?

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