title: An envelope domain III-based chimeric antigen produced in Pichia pastoris elicits neutralizing antibodies against all four dengue virus serotypes.
abstract: There is currently no vaccine to prevent dengue (DEN) virus infection, which is caused by any one of four closely related serotypes, DEN-1, DEN-2, DEN-3, or DEN-4. A DEN vaccine must be tetravalent, because immunity to a single serotype does not offer cross-protection against the other serotypes. We have developed a novel tetravalent chimeric protein by fusing the receptor-binding envelope domain III (EDIII) of the four DEN virus serotypes. This protein was expressed in the yeast, Pichia pastoris, and purified to near homogeneity in high yields. Antibodies induced in mice by the tetravalent protein, formulated in different adjuvants, neutralized the infectivity of all four serotypes. This, coupled with the high expression potential of the P. pastoris system and easy one-step purification, makes the EDIII-based recombinant protein a potentially promising candidate for the development of a safe, efficacious, and inexpensive, tetravalent DEN vaccine.
authors.affiliation: Recombinant Gene Products Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
authors.forename: Behzad
authors.initials: B
authors.lastname: Etemad
authors.forename: Gaurav
authors.initials: G
authors.lastname: Batra
authors.forename: Rajendra
authors.initials: R
authors.lastname: Raut
authors.forename: Satinder
authors.initials: S
authors.lastname: Dahiya
authors.forename: Saima
authors.initials: S
authors.lastname: Khanam
authors.forename: Sathyamangalam
authors.initials: S
authors.lastname: Swaminathan
authors.forename: Navin
authors.initials: N
authors.lastname: Khanna
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D000956:Antigens, Viral / Q000276:immunology*; D002460:Cell Line; D006224:Cricetinae; D009033:Culicidae; D003715:Dengue / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D053059:Dengue Vaccines / Q000276:immunology; D003716:Dengue Virus / Q000145:classification / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005818:Genetic Engineering; D000882:Haplorhini; D051379:Mice; D008807:Mice, Inbred BALB C; D010843:Pichia / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D012703:Serotyping; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D053059:Dengue Vaccines; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins