title: Multivalent fusion protein vaccine for lymphatic filariasis.
abstract: Lymphatic filariasis affects approximately 3% of the whole world population. Mass drug administration is currently the major control strategy to eradicate this infection from endemic regions by year 2020. Combination drug treatments are highly efficient in controlling the infection. However, there are no effective vaccines available for human or animal lymphatic filariasis despite the identification of several subunit vaccines. Lymphatic filariasis parasites are multicellular organisms and potentially use multiple mechanisms to survive in the host. Therefore, there is a need to combine two or more vaccine candidate antigens to achieve the desired effect. In this study we combined three well characterized vaccine antigens of Brugia malayi, heat shock protein 12.6 (HSP12.6), Abundant Larval transcript-2 (ALT-2) and tetraspanin large extra cellular loop (TSP-LEL) as a multivalent fusion vaccine. Putative immune individuals carry circulating antibodies against all three antigens. Depletion of these antigen specific antibodies from the sera samples removed the ability of the sera to participate in the killing of B. malayi L3 in an antibody dependent cellular cytotoxicity (ADCC) mechanism. Vaccination trials in mice with a bivalent [HSP12.6+ALT-2 (HA), HSP12.6+TSP-LEL (HT) or TSP-LEL+ALT-2 (TA)] or trivalent [HSP12.6+ALT-2+TSP-LEL (HAT)] vaccines using DNA, protein or heterologous prime boost regimen showed that trivalent HAT vaccine either as protein alone or as heterologous prime boost vaccine could confer significant protection (95%) against B. malayi L3 challenge. Immune correlates of protection suggest a Th1/Th2 bias. These finding suggests that the trivalent HAT fusion protein is a promising prophylactic vaccine against lymphatic filariasis infection in human.
authors.affiliation: Department of Biomedical Sciences, University of Illinois, College of Medicine at Rockford, IL 61107, USA.
authors.forename: Gajalakshmi
authors.initials: G
authors.lastname: Dakshinamoorthy
authors.forename: Abhilash Kumble
authors.initials: AK
authors.lastname: Samykutty
authors.forename: Gnanasekar
authors.initials: G
authors.lastname: Munirathinam
authors.forename: Maryada Venkatarami
authors.initials: MV
authors.lastname: Reddy
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Kalyanasundaram
mesh_terms: D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D000917:Antibody Formation; D000947:Antigens, Helminth / Q000276:immunology*; D017178:Brugia malayi; D004605:Elephantiasis, Filarial / Q000517:prevention & control*; D006360:Heat-Shock Proteins / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D059470:Tetraspanins / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014612:Vaccines / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology
chemical_list: C521555:ALT-2 protein, Brugia malayi; D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D006360:Heat-Shock Proteins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D059470:Tetraspanins; D014612:Vaccines; D019444:Vaccines, DNA