Multivalent fusion protein vaccine for lymphatic filariasis

• Published in: Vaccine Vol. 31; no. 12; pp. 1616 - 1622
• Main Authors: Dakshinamoorthy, Gajalakshmi, Samykutty, Abhilash Kumble, Munirathinam, Gnanasekar, Reddy, Maryada Venkatarami, Kalyanasundaram, Ramaswamy
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 15.03.2013; Elsevier; Elsevier Limited
• Subjects: Abundant Larval transcript-2; Allergy and Immunology; Animals; antibodies; Antibodies, Helminth - blood; Antibody dependent cellular cytotoxicty; Antibody Formation; antigens; Antigens, Helminth - immunology; Applied microbiology; Biological and medical sciences; Brugia malayi; Cloning; Colleges & universities; combination drug therapy; cytotoxicity; Deoxyribonucleic acid; DNA; Drug dosages; Elephantiasis, Filarial - prevention & control; filariasis; Fundamental and applied biological sciences. Psychology; heat shock proteins; Heat-Shock Proteins - immunology; human diseases; Human subjects; Humans; Immune response; Immunity, Cellular; larvae; Lymphatic filariasis; Medical research; Mice; Mice, Inbred BALB C; Microbiology; Multivalent vaccine; Parasites; Proteins; Recombinant Fusion Proteins - immunology; Recombinant Proteins - immunology; Small heat shock proteins; subunit vaccines; Tetraspanin; Tetraspanins - immunology; Th1 Cells - immunology; Th2 Cells - immunology; vaccination; Vaccines; Vaccines - immunology; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, DNA - immunology; Vector-borne diseases; Antibody dependent cellular cytotoxicty; Small heat shock proteins; Abundant Larval transcript-2; Lymphatic filariasis; Multivalent vaccine; Tetraspanin; Antibody; Cardiovascular disease; Vaccine; Parasitosis; Helminthiasis; Lymphatic vessel disease; Infection; Messenger RNA; Nematode disease; Heat shock protein; Fusion protein
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2012.09.055

► Endemic normals carried circulating antibodies against HSP12.6, ALT-2 and TSP. ► These antibodies are involved in killing of B. malayi L3 in ADCC assay. ► Vaccination trials in mice showed >95% protection with rBmHAT. ► rBmHAT vaccination elicited both Th1 and Th2 mixed type immune response. 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.