Induction of Protective Immunity Against Larval Onchocerca volvulus in a Mouse Model

Lange, Anna; Yutanawiboonchai, Wiboonchai; Lok, James B.; Trpis, Milan; Abraham, David

doi:10.4269/ajtmh.1993.49.783

Cited by 59 publications

(39 citation statements)

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“…Induction of protective immunity using heterologous parasites is supported by the cross protection studies in which irradiated B. pahangi conferred protection against B. malayi (4); O. linealis larvae induced immunity against O. volvulus (27) and cross protection between different genera (24). These reports as well as our humoral immune response studies indicate that the ALT-2 gene could be used as a vaccine against brugian and bancroftian filariasis.…”

Section: Discussionmentioning

confidence: 92%

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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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Section: Discussionmentioning

confidence: 92%

“…These include irradiated B. malayi L3 larvae in monkeys (43) and mice (1) and irradiated O. volvulus larvae in mice (27), as well as dogs previously treated for Dirofilaria immitis infection with ivermectin (18). However, a vaccine candidate has yet to reach clinical trial in humans.…”

Section: Discussionmentioning

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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“…Accordingly, in several hosts challenged with a range of filarial species, 50-100% protective efficacy has been reported after inoculation with irradiated L 3 . Thus, O. volvulus (25), Brugia pahangi (26), and Litomosoides sigmodontis (27) have been used in murine (surrogate) hosts. Natural host-filaria systems in which significant protection has been demonstrated include Loa loa in mandrills (28), Acanthocheilonema viteae in jirds (29), and Dirofilaria immitis (30) in dogs.…”

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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“…For the immunolocalization of the parasite antigens corresponding to the five recombinant antigens, thin sections of embedded worms were incubated with affinity-purified antibodies against each of the individual antigens, followed by incubation with a suspension of 15-nm gold particles coated with protein A, as described previously (25,37,40). In addition, thin sections of molting L3 were probed with normal mouse serum and serum obtained from mice immunized with irradiated L3 and which developed protective immunity to challenge infections (33). Sections were incubated with the immune mouse a EST, expressed sequence tag.…”

Section: Methodsmentioning

confidence: 99%

“…Diffusion chambers were used in the mouse model to contain the larvae and thus afford an efficient method for recovery of the parasites and for analysis of the micro environment in which the parasites were found. Cellular infiltrate into diffusion chambers implanted in immunized mice contained high numbers of eosinophils (33). Protective immunity in the mice to larval O. volvulus was dependent on IL-4 and IL-5 and not IFN-␥ (28,34).…”

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confidence: 99%

Development of a Recombinant Antigen Vaccine against Infection with the Filarial WormOnchocerca volvulus

Abraham

Leon

et al. 2001

Infect Immun

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Efforts to control Onchocerca volvulus, the etiologic agent of river blindness, have been limited to vector control and drug treatment to eliminate microfilariae, with no means available to prevent infection. The goal of this study was to develop a vaccine against this infection using recombinant antigens that are expressed in the early larval stages of the parasite. Five recombinant antigens, Ov7, Ov64, OvB8, Ov9M, and Ov73k, were identified by screening adult and larval cDNA libraries with antibodies from immune humans, chimpanzees, or rabbits. When mice were immunized with the five individual recombinant antigens, statistically significant reductions in parasite survival were induced in mice immunized with Ov7, OvB8, or Ov64, when administered in alum but not when injected in Freund's complete adjuvant (FCA). Live larvae recovered from control and immunized mice were analyzed to determine their developmental stages. A decrease in the percentage of larvae molting from the third stage to the fourth stage was observed with mice immunized with Ov7, Ov64, or OvB8 in alum but not with mice immunized with Ov9 and Ov73k or with mice immunized with any of the five antigens in FCA.

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Induction of Protective Immunity Against Larval Onchocerca volvulus in a Mouse Model

Cited by 59 publications

References 0 publications

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

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

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

Development of a Recombinant Antigen Vaccine against Infection with the Filarial WormOnchocerca volvulus

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