| Autor: |
Nayak, Amiya R., Tinge, Steven A., Tart, Rebecca C., McDaniel, Larry S., Briles, David E., Curtiss, Roy |
| Zdroj: |
Infection and Immunity; August 1998, Vol. 66 Issue: 8 p3744-3751, 8p |
| Abstrakt: |
ABSTRACTA live oral recombinant Salmonellavaccine strain expressing pneumococcal surface protein A (PspA) was developed. The strain was attenuated with Δcya Δcrpmutations. Stable expression of PspA was achieved by the use of the balanced-lethal vector-host system, which employs an asddeletion in the host chromosome to impose an obligate requirement for diaminopimelic acid. The chromosomal Δasdmutation was complemented by a plasmid vector possessing the asd+gene. A portion of the pspAgene from Streptococcus pneumoniaeRx1 was cloned onto a multicopy Asd+vector. After oral immunization, the recombinantSalmonella-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 Salmonellastrain induced significant anti-PspA immunoglobulin G titers in serum and vaginal secretions. Polyclonal sera from orally immunized mice detected PspA on the S. pneumoniaecell surface as revealed by immunofluorescence. Oral immunization of BALB/cJ mice with the PspA-producing Salmonellastrain elicited antibody to PspA and resistance to challenge by the mouse-virulent human clinical isolate S. pneumoniaeWU2. Immune sera from orally immunized mice conferred passive protection against otherwise lethal intraperitoneal or intravascular challenge with strain WU2. |
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