A live recombinant avirulent oral Salmonella vaccine expressing pneumococcal surface protein A induces protective responses against Streptococcus pneumoniae.
A live oral recombinant Salmonella vaccine strain expressing pneumococcal surface protein A (PspA) was developed. The strain was attenuated with Deltacya Deltacrp mutations. Stable expression of PspA was achieved by the use of the balanced-lethal vector-host system, which employs an asd deletion in the host chromosome to impose an obligate requirement for diaminopimelic acid. The chromosomal Deltaasd mutation was complemented by a plasmid vector possessing the asd+ gene. A portion of the pspA gene from Streptococcus pneumoniae Rx1 was cloned onto a multicopy Asd+ vector. After oral immunization, the recombinant Salmonella-PspA vaccine strain colonized the Peyer's patches, spleens, and livers of BALB/cByJ and CBA/N mice and stimulated humoral and mucosal antibody responses. Oral immunization of outbred New Zealand White rabbits with the recombinant Salmonella strain induced significant anti-PspA immunoglobulin G titers in serum and vaginal secretions. Polyclonal sera from orally immunized mice detected PspA on the S. pneumoniae cell surface as revealed by immunofluorescence. Oral immunization of BALB/cJ mice with the PspA-producing Salmonella strain elicited antibody to PspA and resistance to challenge by the mouse-virulent human clinical isolate S. pneumoniae WU2. Immune sera from orally immunized mice conferred passive protection against otherwise lethal intraperitoneal or intravascular challenge with strain WU2.
Department of Biology, Washington University, St. Louis, Missouri 63130, USA.
A R
AR
Nayak
S A
SA
Tinge
R C
RC
Tart
L S
LS
McDaniel
D E
DE
Briles
R
R
Curtiss
D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000235:genetics / Q000276:immunology*; D004341:Drug Evaluation; D005260:Female; D005453:Fluorescence; D015870:Gene Expression; D005822:Genetic Vectors; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D011008:Pneumococcal Infections / Q000517:prevention & control*; D011817:Rabbits; D012486:Salmonella typhimurium; D013296:Streptococcus pneumoniae / Q000276:immunology*; D014018:Tissue Distribution; D014613:Vaccines, Attenuated / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; C051592:pneumococcal surface protein A