Prediction of Brugia malayi Antigenic Peptides: Candidates for Synthetic Vaccine Design Against Lymphatic Filariasis

Abstract

Brugia malayi is a threadlike nematode cause's swelling of lymphatic organs, condition well known as lymphatic filariasis; till date no invention made to effectively address lymphatic filariasis. In this analysis we a have predicted suitable antigenic peptides from Brugia malayi antigen protein for peptide vaccine design against lymphatic filariasis based on cross protection phenomenon as, an ample immune response can be generated with a single protein subunit. We found MHC class II binding peptides of Brugia malayi antigen protein are important determinant against the diseased condition. The analysis shows Brugia malayi antigen protein having 505 amino acids, which shows 497 nonamers. In this assay, we have predicted MHC-I binding peptides for 8mer_H2_Db (optimal score- 15.966), 9mer_H2_Db (optimal score- 15.595), 10mer_H2_Db (optimal score- 19.405), 11mer_H2_Dballeles (optimal score- 23.801). We also predicted the SVM based MHCII-IAb nonamers, 51-FQQIDPLDA, 442-FAAIACLVH, 206-YLNPFGHQF, 167-WYVIMAACY, 367-YAMIVIRLL, 434- LVITTAANF, 176-LDSYCLWKP, 435-VITTAANFA, 364-WPGYAMIVI (optimal score- 13.963); MHCII-IAd nonamers, 52-QQIDPLDAE, 171-MAACYLDSY, 239-QWRSVILCN, 168-YVIMAACYL, 3-QYLSVHSLS, 322-EILLHAKVV, 417- LGIIASFVS, 396-KAIFLAHFG, 167-WYVIMAACY, 269-LALHCINVI, 93-FINKAAPKQ, 259-NCIIVLKAF, 79- QGVLLIIPR, 22-TILQRSQAI, 63-RGFVYGNVS, 109-NISSLAFET,(optimal score- 16.748); and MHCII-IAg7 nonamers 171-MAACYLDSY, 73-KIVNGAQGV, 259-NCIIVLKAF, 209-PFGHQFSFE, 102-SCDTLLKNI, 25-QRSQAIRIV, 444- AIACLVHLF, 88-SLVNGFINK, 252-FPRHQLLNC, 471-RFVLANDNE, 52-QQIDPLDAE, 469-HRRFVLAND, 457- SNRHYFLAD, 362-KSWPGYAMI, 476-NDNEGEDFE, 370-IVIRLLQAL (optimal score- 19.847) which represents potential binders from Brugia malayi antigen protein. The method integrates prediction of MHC class I binding proteasomal C-terminal cleavage peptides and Eighteen potential antigenic peptides at average propensity 1.063 having highest local hydrophilicity. Thus a small antigen fragment can induce immune response against whole antigen. This approach can be applied for designing subunit and synthetic peptide vaccines.

Prospects of developing a prophylactic vaccine against human lymphatic filariasis – evaluation of protection in non-human primates

“…A prophylactic vaccine has the potential to protect the at-risk population from getting the infection and possibly boost immunity by natural exposure to a low-level infection in endemic areas. Our group and others have been working during the last decade to develop an effective prophylactic vaccine against LF (Denham, 1980; Dissanayake et al, 1995; Gregory et al, 1997; Anand et al, 2008; Gnanasekar et al, 2008; Vedi et al, 2008; Veerapathran et al, 2009; Anand et al, 2011; Kalyanasundaram and Balumuri, 2011; Babayan et al, 2012; Dakshinamoorthy et al, 2012; Anugraha et al, 2013; Dakshinamoorthy et al, 2013a; Gomase et al, 2013; Arumugam et al, 2014; Gupta et al, 2016). A multivalent r Bm HAT vaccine developed in our laboratory showed significant protection against challenge infections in rodent models (Dakshinamoorthy and Kalyanasundaram, 2013; Dakshinamoorthy et al, 2013a).…”

“…These findings brought to light the critical need for a more sustainable approach such as a prophylactic vaccine together with MDA to interrupt the transmission and control of LF infection in endemic areas (Ramaswamy 2016). Our laboratory and others have identified and characterized several potential candidate vaccine antigens of LF and evaluated their vaccine potential in rodent models (Denham, 1980; Dissanayake et al, 1995; Gregory et al, 1997; Anand et al, 2008, 2011; Gnanasekar et al, 2008; Vedi et al, 2008; Veerapathran et al, 2009; Kalyanasundaram and Balumuri, 2011; Babayan et al, 2012; Dakshinamoorthy et al, 2012; Anugraha et al, 2013; Dakshinamoorthy et al, 2013a; Gomase et al, 2013; Arumugam et al, 2014; Gupta et al, 2016). Among the various antigens that we characterized, four antigens, abundant larval transcript-2 (ALT-2) (Anand et al, 2008; Kalyanasundaram and Balumuri, 2011; Madhumathi et al, 2017), heat shock protein (HSP) 12.6 (Dakshinamoorthy et al, 2012), thioredoxin peroxidase-2 (TPX-2) (Anand et al, 2008; Anugraha et al, 2013) and tetraspanin large extracellular loop (TSP-LEL) (Gnanasekar et al, 2008; Dakshinamoorthy et al, 2013a) gave excellent protection in rodent models.…”

SVM based Prediction of Major Histocompatibility Complex Binders: Identification and Analysis of Dracunculus medinensis Peptide

“…Where T helper cells trigger an immune response by inflammation and swelling due to phagocytes or may lead to an antibody-mediated immune response via B-cell activation. Since MHCs have a key role in immune system by stimulating cellular and humoral immunity against NADH dehydrogenase subunit 6 (mitochondrion) from D. medinensis and are used for controlling specific immunological processes by creating peptides to bind to specific MHC alleles and this binding affinity to specific peptides are used for designing synthetic peptide vaccines [37][38][39][40].…”

Computational Approach to Identify the Major Histocompatibility Complex Binding Antigenic Peptides from 'Ascariasis'

“…Where T helper cells trigger an immune response by inflammation and swelling due to phagocytes or may lead to an antibody-mediated immune response via B-cell activation. Since MHCs have a key role in immune system by stimulating cellular and humoral immunity against antigenic peptide are used for controlling specific immunological processes by creating peptides to bind to specific MHC alleles and this binding affinity to specific peptides are used for designing synthetic peptide vaccines [40][41][42][43].…”