title: Effect of homologous and heterologous prime-boost on the immune response to recombinant plague antigens.
abstract: Among the pathogens that have been identified as potential agents of biological warfare or bioterrorism, Yersinia pestis is one of the main concerns due to the severity and potential transmissibility of the pneumonic form of the disease in humans. There are no approved vaccines for protection against pneumonic plague, but a Y. pestis-derived fusion protein (F1-V) has shown great promise as a protective antigen in murine studies. In the current study, we examine different prime-boost regimens, including parenteral, mucosal, and transcutaneous delivery, in order to explore the effect of changing the route of prime and boost on the ability of recombinant F1-V to promote the development of long-lasting, high-titer antibodies. The most significant findings of the study reported here are that (1) intranasal and subcutaneous immunizations are both effective and essentially equivalent for induction of serum and bronchioalveolar anti-F1-V IgG1 responses when a single booster dose is administered by the same (homologous) route, (2) heterologous boosting can be as or more effective than homologous boosting for induction of either serum or bronchioalveolar anti-F1-V IgG1 responses, and (3) anti-F1 and anti-V total IgG responses were highest in animals primed intranasally and boosted by any route when compared to animals primed transcutaneously or subcutaneously. As with previously published studies, there were still significant levels of circulating anti-F1-V antibodies 1 year post-primary immunization. These studies provide important insights into the development of new-generation biodefense vaccines.
authors.affiliation: Department of Microbiology and Immunology, Program in Molecular Pathogenesis and Immunity, 1430 Tulane Avenue, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Audrey
authors.initials: A
authors.lastname: Glynn
authors.forename: Lucy C
authors.initials: LC
authors.lastname: Freytag
authors.forename: John D
authors.initials: JD
authors.lastname: Clements
mesh_terms: D000276:Adjuvants, Immunologic; D000279:Administration, Cutaneous; D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis / Q000096:biosynthesis*; D001427:Bacterial Toxins / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology; D029968:Escherichia coli Proteins / Q000276:immunology; D005260:Female; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007279:Injections, Subcutaneous; D051379:Mice; D010931:Plague Vaccine / Q000008:administration & dosage / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007074:Immunoglobulin G; D010931:Plague Vaccine; D014614:Vaccines, Synthetic; C027538:heat-labile enterotoxin, E coli