Immunity to Onchocerciasis: Identification of a Putatively Immune Population in a Hyperendemic Area of Ecuador

Elson, Lynne; Guderian, Ronald H.; Araujo, Edmundo; Bradley, Janette E.; Days, Alison; Nutman, Thomas B.

doi:10.1093/infdis/169.3.588

Cited by 73 publications

(52 citation statements)

References 29 publications

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“…At a minimum, these observations indicate the existence of considerable heterogeneity in susceptibility to O. ochengi among Gudali cattle (19), if not distinct ''resistant'' and ''permissive'' populations. In regions that are hyperendemic for O. volvulus, human PI subpopulations have been identified in both West Africa (20) and Latin America (21). This phenomenon has been the focus of intensive immunological study (8)(9)(10)22), and although several characteristic features have been identified in PI, including a discrete distribution of HLA-D alleles (20), it has not been possible to categorically exclude the influence of risk factors such as occupation, social status, and migration.…”

Section: Discussionmentioning

confidence: 99%

In a bovine model of onchocerciasis, protective immunity exists naturally, is absent in drug-cured hosts, and is induced by vaccination

Tchakouté

Graham

Jensen

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Onchocerciasis (river blindness) is a major parasitic disease of humans in sub-Saharan Africa caused by the microfilarial stage of the nematode Onchocerca volvulus. Using Onchocerca ochengi, a closely related species which infects cattle and is transmitted by the same black fly vector (Simulium damnosum sensu lato) as O. volvulus, we have conducted longitudinal studies after either natural field exposure or experimental infection to determine whether, and under what circumstances, protective immunity exists in onchocerciasis. On the basis of the adult worm burdens (nodules) observed, we determined that cattle reared in endemic areas without detectable parasites (putatively immune) were significantly less susceptible to heavy field challenge than agematched, naïve controls (P ‫؍‬ 0.002), whereas patently infected cattle, cured of infection by adulticide treatment with melarsomine, were fully susceptible. Cattle immunized with irradiated third-stage larvae were significantly protected against experimental challenge (100% reduction in median nodule load, P ‫؍‬ 0.003), and vaccination also conferred resistance to severe and prolonged field challenge (64% reduction in median nodule load, P ‫؍‬ 0.053; and a significant reduction in microfilarial positivity rates and density, P < 0.05). These results constitute evidence of protective immunity in a naturally evolved host-Onchocerca sp. relationship and provide proof-of-principle for immunoprophylaxis under experimental and field conditions. filariasis ͉ irradiation ͉ larvae ͉ ochengi ͉ Onchocerca

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Section: Discussionmentioning

confidence: 99%

In a bovine model of onchocerciasis, protective immunity exists naturally, is absent in drug-cured hosts, and is induced by vaccination

Tchakouté

Graham

Jensen

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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“…Immunoscreening was undertaken with sera obtained from a subgroup of O. volvulusinfected and immune subjects (putatively immune, PI) from an endemic region of Ecuador (13). Infection status was documented by clinical history, nodule palpation, ophthalmological evaluation for ocular microfilariae, and by parasitological evaluation through skin snips examination supplemented by PCR of the skin for an Onchocerca volvulus-specific repeat DNA sequence (45).…”

Section: Methodsmentioning

confidence: 99%

“…With the objective of identification of such vaccine candidates, we adopted an immunoscreening approach using pooled immune sera from a well-defined human population residing in an onchocerciasis-endemic region of Ecuador (13) to screen a Brugia malayi L3 stage cDNA library. When one prominent recombinant was identified using this approach, it was decided to evaluate it as a protective antigen in lymphatic filariasis.…”

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confidence: 99%

The Larval Specific Lymphatic Filarial ALT‐2: Induction of Protection Using Protein or DNA Vaccination

Ramachandran

Kumar

Rami

et al. 2004

Microbiology and Immunology

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Genes from the infective stage of lymphatic filarial parasites expressed at the time of host invasion have been identified as potential vaccine candidates. By screening an L3 cDNA library with sera from uninfected longstanding residents of an area endemic for onchocerciasis, so‐called “endemic normals” (EN), we have cloned and characterized one such gene termed the abundant larval transcript two (ALT‐2). The stage specificity of ALT‐2 gene transcription and protein synthesis was confirmed by PCR using gene‐specific primers, and by western blot analysis of protein extracts from various stages of the parasite life cycle using specific antisera. Significant differences in antibody response to the recombinant ALT‐2 were observed in endemic populations with differing clinical manifestations of lymphatic filariasis with an antibody response present in sera from 18 of 25 (72%) EN subjects compared to 9 of 25 (36%) with subclinical microfilaracmia (MF) and 14 of 25 (52%) of those with chronic lymphatic obstruction (CP) (P=0.01 for comparison of EN to CP or to MF). This differential responsiveness suggests that the protective immunity postulated to account for their uninfected status might be associated with a response to this protein. When the utility of ALT‐2 as a vaccine candidate was tested in a murine model using either recombinant protein or a DNA vaccine construct, statistically significant protection was observed when compared to a control filarial gene product expressed across all stages of the parasite lifecycle (SXP‐1; P=0.02 for protein and P=0.01 for the DNA vaccine) or compared to adjuvant alone. This level of protection indicates that this vaccine is a promising candidate for further development.

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“…These persons have been described as putatively immune individuals. 22 Furthermore, we studied 33 sera from persons living in endemic areas in Togo, who were exposed to O. volvulus transmission, but did not harbor microfilariae in their skin (Soboslay P, unpublished data). Sera from Cameroon were obtained from characterized patients living near the Sanaga River in the Central Province of Cameroon, a forest region endemic for onchocerciasis.…”

Section: Seramentioning

confidence: 99%

Sensitive and specific serodiagnosis of onchocerciasis with recombinant hybrid proteins.

Nde¹,

Pogonka²,

Bradley³

et al. 2002

The American Journal of Tropical Medicine and Hygiene

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Abstract. Onchocerciasis remains a major health hazard in many tropical countries. However, the existing tools for diagnosis of the disease have limitations, particularly regarding the detection of low level or early infections. To design an optimized reagent, we exploited the high antibody reactivity of patient sera against the Onchocerca volvulus proteins Ov20 and Ov33, which have been described as highly sensitive and specific immunodiagnostic reagents for producing hybrid proteins. The construct OvH2 was composed of Ov20 fused to Ov33, while OvH3 consisted of the C-terminus of Ov20 linked to Ov33. When these constructs were tested with sera from patients with onchocerciasis and control sera, OvH2 showed a sensitivity of 98.5% and a specificity of 97.7% and OvH3 showed a sensitivity of 98.5% and a specificity of 95.35%. All non-responders were from Ecuador. These results surpass those of existing single recombinant antigens, suggesting that our hybrid proteins combined the sensitivity of the two parent proteins. Tests based on OvH2 should prove suitable for monitoring onchocerciasis control programs and individual diagnosis.

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Immunity to Onchocerciasis: Identification of a Putatively Immune Population in a Hyperendemic Area of Ecuador

Cited by 73 publications

References 29 publications

In a bovine model of onchocerciasis, protective immunity exists naturally, is absent in drug-cured hosts, and is induced by vaccination

In a bovine model of onchocerciasis, protective immunity exists naturally, is absent in drug-cured hosts, and is induced by vaccination

The Larval Specific Lymphatic Filarial ALT‐2: Induction of Protection Using Protein or DNA Vaccination

Sensitive and specific serodiagnosis of onchocerciasis with recombinant hybrid proteins.

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