Induction of Protective Immunity in Dogs to Infection with Dirofilaria Immitis Using Chemically-Abbreviated Infections

Grieve, Robert B.; Abraham, David; Mika-Grieve, Marcia; Seibert, Barbara P.

doi:10.4269/ajtmh.1988.39.373

Cited by 57 publications

(30 citation statements)

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“…Based on this conclusion, the level of larval killing in immunized mice would actually be higher than that reported in this study, since all of the remaining L3 would be killed when they molted into L4. Evidence from immunization trials against D. immitis in dogs has shown that the protective immune response killed approximately 50% of challenge larvae at 3 weeks postchallenge but killed 98% at 6 months postchallenge (23). It is therefore probable that the level of protective immunity induced by the recombinant antigens in the present study would be augmented if the challenge infection larvae were recovered at a later time point.…”

Section: Discussionmentioning

confidence: 76%

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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Section: Discussionmentioning

confidence: 76%

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

Abraham

Leon

et al. 2001

Infect Immun

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Section: Dirofilaria Immitismentioning

confidence: 84%

“…Chemically abbreviated infections provide moderate to excellent protection (47 to 98%) in this model, depending on the protocol used (143,149). The best results of 98% protection were obtained with three abbreviated infections of 400, 150, and 300 larvae 532, 420, and 329 days prior to challenge infection, followed by ivermectin 2 months after each priming infection (149). Interestingly, in one study, inoculation of animals with Freund's complete adjuvant, which skews the immune system toward a type 1 phenotype instead of the type 2 phenotype (which typically occurs in response to helminths), increased protective immunity obtained by chemical abbreviation of infection from 50% to 72% (143).…”

Section: Dirofilaria Immitismentioning

confidence: 99%

A Comprehensive, Model-Based Review of Vaccine and Repeat Infection Trials for Filariasis

et al. 2013

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SUMMARY Filarial worms cause highly morbid diseases such as elephantiasis and river blindness. Since the 1940s, researchers have conducted vaccine trials in 27 different animal models of filariasis. Although no vaccine trial in a permissive model of filariasis has provided sterilizing immunity, great strides have been made toward developing vaccines that could block transmission, decrease pathological sequelae, or decrease susceptibility to infection. In this review, we have organized, to the best of our ability, all published filaria vaccine trials and reviewed them in the context of the animal models used. Additionally, we provide information on the life cycle, disease phenotype, concomitant immunity, and natural immunity during primary and secondary infections for 24 different filaria models.

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“…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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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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Induction of Protective Immunity in Dogs to Infection with Dirofilaria Immitis Using Chemically-Abbreviated Infections

Cited by 57 publications

References 0 publications

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

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

A Comprehensive, Model-Based Review of Vaccine and Repeat Infection Trials for Filariasis

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

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