Novel phage display-based subtractive screening to identify vaccine candidates of Brugia malayi.
This study describes a novel phage display method based on an iterative subtraction strategy to identify candidate vaccine antigens of Brugia malayi. A cDNA library of the infective larval stage of B. malayi expressed on the surface of T7 phage was sequentially screened with sera samples from human subjects showing different manifestations of the disease. Antigens that selectively and specifically bind to immune sera were then enriched using a multi-step panning procedure. This strategy identified five antigens, four of which were previously reported (ALT-2, TPX-2, VAH and COX-2) and the other one was a novel cuticular collagen (Col-4). Sera from immune individuals specifically recognized all the five antigens. However, ALT-2 appeared to be the most predominantly recognized antigen by the immune sera. Therefore, it was decided to evaluate the vaccine potential of recombinant ALT-2 (rALT-2) in a mouse and jird model. The results presented show that immunization with rALT-2 conferred over 73% protection against a challenge infection in the jird model and over 64% protection in the mouse model. The present study suggests that phage display-based cDNA screening may be a powerful tool to identify candidate vaccine antigens of infectious agents.
Department of Biomedical Sciences, College of Medicine, University of Illinois, Rockford, IL 61107, USA.
Munirathinam
M
Gnanasekar
Kakaturu V N
KV
Rao
Yi-Xun
YX
He
Pankaj K
PK
Mishra
Thomas B
TB
Nutman
Perumal
P
Kaliraj
Kalyanasundaram
K
Ramaswamy
D000595:Amino Acid Sequence; D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood*; D000947:Antigens, Helminth / Q000008:administration & dosage / Q000276:immunology*; D017178:Brugia malayi / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D003094:Collagen / Q000235:genetics; D003576:Electron Transport Complex IV / Q000235:genetics; D004605:Elephantiasis, Filarial / Q000276:immunology / Q000517:prevention & control*; D005849:Gerbillinae; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007114:Immunization; D051379:Mice; D008969:Molecular Sequence Data; D019151:Peptide Library; D017422:Sequence Analysis, DNA; D014612:Vaccines / Q000008:administration & dosage / Q000276:immunology*
D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D007106:Immune Sera; D019151:Peptide Library; D014612:Vaccines; D003094:Collagen; C117108:cytochrome C oxidase subunit II; D003576:Electron Transport Complex IV