Current Approaches to the Development of a Vaccine Against Filarial Nematodes

Lustigman, Sara

doi:10.1002/9781118393321.ch28

Cited by 4 publications

(5 citation statements)

References 72 publications

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“…However, a recent survey of almost 400 NTD experts indicated that many believe onchocerciasis will never be eliminated through MDA with ivermectin solely [ 11 ]. Hence, to strengthen the current elimination programs additional tools are necessary to prevent infection, cure infection and interrupt transmission, and thus complement current MDA programs [ 12 – 14 ]. An efficacious vaccine against onchocerciasis will be an invaluable tool in the effort to eliminate onchocerciasis from humans.…”

Section: Introductionmentioning

confidence: 99%

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Vaccination of Gerbils with Bm-103 and Bm-RAL-2 Concurrently or as a Fusion Protein Confers Consistent and Improved Protection against Brugia malayi Infection

et al. 2016

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BackgroundThe Brugia malayi Bm-103 and Bm-RAL-2 proteins are orthologous to Onchocerca volvulus Ov-103 and Ov-RAL-2, and which were selected as the best candidates for the development of an O. volvulus vaccine. The B. malayi gerbil model was used to confirm the efficacy of these Ov vaccine candidates on adult worms and to determine whether their combination is more efficacious.Methodology and Principle FindingsVaccine efficacy of recombinant Bm-103 and Bm-RAL-2 administered individually, concurrently or as a fusion protein were tested in gerbils using alum as adjuvant. Vaccination with Bm-103 resulted in worm reductions of 39%, 34% and 22% on 42, 120 and 150 days post infection (dpi), respectively, and vaccination with Bm-RAL-2 resulted in worm reductions of 42%, 22% and 46% on 42, 120 and 150 dpi, respectively. Vaccination with a fusion protein comprised of Bm-103 and Bm-RAL-2 resulted in improved efficacy with significant reduction of worm burden of 51% and 49% at 90 dpi, as did the concurrent vaccination with Bm-103 and Bm-RAL-2, with worm reduction of 61% and 56% at 90 dpi. Vaccination with Bm-103 and Bm-RAL-2 as a fusion protein or concurrently not only induced a significant worm reduction of 61% and 42%, respectively, at 150 dpi, but also significantly reduced the fecundity of female worms as determined by embryograms. Elevated levels of antigen-specific IgG were observed in all vaccinated gerbils. Serum from gerbils vaccinated with Bm-103 and Bm-RAL-2 individually, concurrently or as a fusion protein killed third stage larvae in vitro when combined with peritoneal exudate cells.ConclusionAlthough vaccination with Bm-103 and Bm-RAL-2 individually conferred protection against B. malayi infection in gerbils, a more consistent and enhanced protection was induced by vaccination with Bm-103 and Bm-RAL-2 fusion protein and when they were used concurrently. Further characterization and optimization of these filarial vaccines are warranted.

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Section: Introductionmentioning

confidence: 99%

“…volvulus parasites, prompted us to utilize at least two complementary animal models which provide distinct advantages for validating vaccine candidates before moving forward to clinical development. This strategy is discussed in detail elsewhere [ 4 , 14 , 18 ]. The O .…”

Section: Introductionmentioning

confidence: 99%

Vaccination of Gerbils with Bm-103 and Bm-RAL-2 Concurrently or as a Fusion Protein Confers Consistent and Improved Protection against Brugia malayi Infection

et al. 2016

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“…In comparison, the average percentage of worms recovered from the lymphatics and lymph nodes of alum control groups and antigen-vaccinated groups was 58 and 56%, respectively (Unpublished data). The recombinant B. malayi proteins used in these experiments are homologs of O. volvulus proteins reviewed elsewhere [ 23 ]. These proteins are E. coli expressed Bm -ALT-1 ( B. malayi abundant larval transcript-1), Pichia expressed Bm -ALT-1, E. coli expressed Bm -ALT-2, E. coli expressed Bm -FAR-1 ( B. malayi fatty acid retinol binding protein), Pichia expressed Bm -FAR-1, E. coli expressed Bm -FAR-2, E. coli expressed Bm -103 ( B. malayi cDNA clone 103), Pichia expressed Bm -103, E. coli expressed Bm -RAL-2 ( B. malayi novel protein reactive against larvae antiserum-2) and Pichia expressed Bm -RAL-2.…”

Section: Discussionmentioning

confidence: 99%

Vaccination with recombinant Brugia malayi cystatin proteins alters worm migration, homing and final niche selection following a subcutaneous challenge of Mongolian gerbils (Meriones unguiculatus) with B. malayi infective larvae

et al. 2014

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BackgroundCysteine protease inhibitors of Brugia malayi have been ascribed to be involved in parasite development as well as to immunomodulate the host’s immune response. In Onchocerca volvulus, Onchocystatin has been shown to induce partial protection in the mouse diffusion chamber vaccination model. In the present study we investigated the impact of vaccination with recombinant Bm-CPI-1 and Bm-CPI-2 proteins on protection against a subcutaneous challenge of B. malayi third stage larvae in gerbils.FindingsVaccination with E. coli derived recombinant B. malayi cysteine protease inhibitors (Bm-CPI-1 or -2) did not confer protection against B. malayi L3 challenge infection in gerbils but altered the homing of a significant number of adult worms from the lymphatics to the heart and lungs.ConclusionBm-CPI vaccination-induced alteration in worm migration is consistent with our previous observations in gerbils vaccinated with B. pahangi excretory-secretory (ES) proteins, which resulted in delayed migration of the L3s and altered the final location of adult worms. Similar observations have also been made in dogs vaccinated with Ancylostoma caninum proteins; an increased number of worms were recovered in the colon and not the expected small intestine. A change in the final niche was also reported in immune versus non-immune hosts of two other gut dwelling nematodes. Vaccination induced alteration of the parasite’s final homing might be a rare or a common phenomenon, which unfortunately is rarely recorded. The reason for the alteration in the final niche selection by adult nematode worms following vaccination is unknown and necessitates further investigation.

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“…However, continued MDA can potentially contribute to the development of drug resistance as reported in onchocerciasis (Osei-Atweneboana et al, 2011). Development and distribution of filarial vaccines is another feasible strategy for the global control and elimination of filariasis (Lustigman, 2012; Prichard et al, 2012). The vaccine candidates of Onchocerca volvulus and lymphatic filariae have been reviewed by Lustigman (2012).…”

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confidence: 99%

“…Development and distribution of filarial vaccines is another feasible strategy for the global control and elimination of filariasis (Lustigman, 2012; Prichard et al, 2012). The vaccine candidates of Onchocerca volvulus and lymphatic filariae have been reviewed by Lustigman (2012). The level of protection reported ranges from 40% to 76%.…”

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confidence: 99%

Vaccination with a genetically modified Brugia malayi cysteine protease inhibitor-2 reduces adult parasite numbers and affects the fertility of female worms following a subcutaneous challenge of Mongolian gerbils (Meriones unguiculatus) with B. malayi infective larvae

Amalakanti

Wei

Ward

et al. 2014

International Journal for Parasitology

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Vaccination of Mongolian gerbils with Brugia malayi cysteine protease inhibitor-2 in which the amino acid Asn66 was mutated to Lys66 (Bm-CPI-2M) resulted in reduced parasite numbers of 48.6% and 48.0 % at 42 and 90 days p.i. with B. malayi L3s. Fertility of female worms was also affected at 90 days p.i. In vitro killing of L3s observed in the presence of gerbil peritoneal exudate cells and anti-Bm-CPI-2M sera suggests antibody-dependent cell-mediated cytotoxicity as a putative protective mechanism. These observations suggest that Bm-CPI-2M is a promising prophylactic and anti-fecundity vaccine candidate.

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Current Approaches to the Development of a Vaccine Against Filarial Nematodes

Cited by 4 publications

References 72 publications

Vaccination of Gerbils with Bm-103 and Bm-RAL-2 Concurrently or as a Fusion Protein Confers Consistent and Improved Protection against Brugia malayi Infection

Vaccination of Gerbils with Bm-103 and Bm-RAL-2 Concurrently or as a Fusion Protein Confers Consistent and Improved Protection against Brugia malayi Infection

Vaccination with recombinant Brugia malayi cystatin proteins alters worm migration, homing and final niche selection following a subcutaneous challenge of Mongolian gerbils (Meriones unguiculatus) with B. malayi infective larvae

Vaccination with a genetically modified Brugia malayi cysteine protease inhibitor-2 reduces adult parasite numbers and affects the fertility of female worms following a subcutaneous challenge of Mongolian gerbils (Meriones unguiculatus) with B. malayi infective larvae

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