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Molecular characterization and evaluation of Onchocerca volvulus-secreted larval acidic protein 1 (SLAP1) as a putative vaccine candidate on endemic population of lymphatic filariasis

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Abstract

Filarial parasites infected nearly 160 million of the global population with onchocerciasis and lymphatic filariasis, and further, a billion of people are estimated to be at risk of infection, rendering them among the most prevalent infectious agents in the world today. Given the complexity of their life cycle and the immune evasion mechanisms of these organisms, development of a vaccine remains to be a long-term challenge. Though a number of immunodominant antigens have been characterized, the presence of homologous proteins in humans or the allelic variants are some of the major drawbacks. One of the extensively studied vaccine candidates is abundant larval transcripts (ALT) family of proteins for the following properties: highly regulated expression, abundance, excreted–secreted product of infective stage larvae, and essentially for parasite establishment and survival in the host. In the present study, stage-specific expression of secreted larval acidic protein 1 (SLAP1) was identified; an ALT orthologue from Onchocerca volvulus was cloned, expressed, and purified as a recombinant protein. Immunogenicity of OvSLAP1 was demonstrated with sera and peripheral blood mononuclear cells from endemic regions of Brugia malayi and Wuchereria bancrofti. OvSLAP1 antibodies were predominated by IgG1 and IgG2 in endemic normal (EN) and chronic pathology (CP) subjects. It has also induced marked cellular response as observed by lymphoproliferation assay. The study revealed that OvSLAP1 can segregate humoral (EN mean optical density (OD) = 0.87 ± 0.035, CP mean OD = 0.59 ± 0.029) and cellular (EN mean stimulation index (SI) = 5.87 ± 0.167, CP mean SI = 3.5 ± 0.134) immune responses between EN and CP individuals (P < 0.001), signifying its prophylactic ability and vitality for protection from filarial infections in endemic population.

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Acknowledgments

The authors are thankful to the Department of Biotechnology (DBT), Government of India, and the University Grants Commission (UGC) for their financial assistance. We would like to convey our genuine thank to Steven A. Williams, Gates Professor of Biological Sciences, Smith College, Northampton, MA for kindly gifting different stages of O. volvulus cDNA libraries and crude extracts. We sincerely thank Dr. K. Gopalrathinam, Senior Entomologist, Zonal Entomology Team, Vellore, Tamilnadu, for his cooperation and support in the sample collection. We would like to thank Dr. Murray Selkirk, Professor of Biochemical Parasitology, Division of Cell and Molecular Biology, Imperial College London, for kindly providing the non-endemic sera samples for the study. Heartfelt thanks to Yang Wu, Division of Molecular Biology and Immunology, Liverpool School of Tropical Medicine, Liverpool, UK for an image of larvae of O. volvulus.

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Correspondence to Perumal Kaliraj.

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Mahalakshmi, N., Aparnaa, R., Ansel Vishal, L. et al. Molecular characterization and evaluation of Onchocerca volvulus-secreted larval acidic protein 1 (SLAP1) as a putative vaccine candidate on endemic population of lymphatic filariasis. Parasitol Res 112, 3203–3211 (2013). https://doi.org/10.1007/s00436-013-3496-y

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Keywords

  • Lymphatic Filariasis
  • Stimulation Index
  • Onchocerciasis
  • Filarial Nematode
  • Filarial Parasite