Immunological evaluation of fusion protein of Brugia malayi abundant larval protein transcript-2 (BmALT-2) and Tuftsin in experimental mice model

Parasite Epidemiol Control. 2019 Feb 7:4:e00092. doi: 10.1016/j.parepi.2019.e00092. eCollection 2019 Feb.

Abstract

Introduction: Filariasis, a neglected tropical helminth disease needs vaccine besides mass drug administration for its successful eradication.

Methods: An attempt was made to produce a fusion protein (P-TUFT-ALT-2) of abundant larval transcript protein-2 and Tuftsin to enhance its immunogenicity. The fusion construct was expressed in Pichia pastoris, a nonexpensive commercial expression system. This study focused on the evaluation of immunological response produced by P-TUFT-ALT-2 in Balb/c mice.

Result and discussion: P-TUFT-ALT-2 showed an enhanced IgG peak titre compared to E. coli expressed E-ALT-2 and P. pastoris expressed P-ALT-2. IgG2b, IgG2a and IgG1 production were predominant indicating a balanced Th1/Th2 response. P-TUFT-ALT-2 also induced about 28% and 9.5% higher splenocyte proliferation over control and E-ALT-2 respectively. Splenocytes produced predominant IFN-γ followed by IL-5, IL-2 and IL-10 specifying a balanced Th1/Th2 response. P-TUFT-ALT-2 showed 55% to 80% with an average of 65% cytotoxicity in B. malayi L3 larvae in in vitro ADCC assay.

Conclusion: This experiment validates P-TUFT-ALT-2 as a potential vaccine candidate for human lymphatic filariasis.

Keywords: Abundant larval transcript-2; Balb/c mice; Lymphatic filariasis; Pichia pastoris; Tuftsin; Vaccine candidate.