title: Immunization of humans with recombinant pneumococcal surface protein A (rPspA) elicits antibodies that passively protect mice from fatal infection with Streptococcus pneumoniae bearing heterologous PspA.
abstract: Pneumococcal surface protein A (PspA), a cross-reactive protein expressed by all pneumococci, is known to elicit an antibody in animals that can passively protect mice from infection with Streptococcus pneumoniae. A phase I trial with recombinant PspA showed the protein to be immunogenic in humans. Pre- and postimmune serum samples from this trial were examined, and human antibody to PspA could protect mice from pneumococcal infection. The serum samples of subjects immunized twice with 125 microg of PspA had >100 times as much antibody per milliliter as was required to consistently protect mice from fatal infection (1.3 microg/dose). At least 98% of PspAs fall into PspA sequence/serologic families 1 or 2. Human antibodies elicited by a family 1 PspA protected against infection with S. pneumoniae expressing either family 1 or 2 PspAs and with strains of all 3 capsular types tested: 3, 6A, and 6B. These studies suggest that PspA may have efficacy as a human vaccine.
authors.affiliation: Departments of Microbiology and Pediatrics, University of Alabama at Birmingham, AL 35294, USA. dbriles@uab.edu
authors.forename: D E
authors.initials: DE
authors.lastname: Briles
authors.forename: S K
authors.initials: SK
authors.lastname: Hollingshead
authors.forename: J
authors.initials: J
authors.lastname: King
authors.forename: A
authors.initials: A
authors.lastname: Swift
authors.forename: P A
authors.initials: PA
authors.lastname: Braun
authors.forename: M K
authors.initials: MK
authors.lastname: Park
authors.forename: L M
authors.initials: LM
authors.lastname: Ferguson
authors.forename: M H
authors.initials: MH
authors.lastname: Nahm
authors.forename: G S
authors.initials: GS
authors.lastname: Nabors
mesh_terms: D000328:Adult; D000818:Animals; D000907:Antibodies, Bacterial / Q000008:administration & dosage / Q000096:biosynthesis* / Q000276:immunology; D000942:Antigens, Bacterial / Q000008:administration & dosage* / Q000096:biosynthesis; D001426:Bacterial Proteins / Q000008:administration & dosage* / Q000096:biosynthesis / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000096:biosynthesis; D003429:Cross Reactions; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D011008:Pneumococcal Infections / Q000517:prevention & control*; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage; D013296:Streptococcus pneumoniae; D014611:Vaccination
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D007074:Immunoglobulin G; D011994:Recombinant Proteins; C051592:pneumococcal surface protein A