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A live oral recombinantSalmonella vaccine strain expressing pneumococcal surface protein A (PspA) was developed. The strain was attenuated with Δcya Δcrp mutations. Stable expression of PspA was achieved by the use of the balanced-lethal vector-host system, which employs anasd deletion in the host chromosome to impose an obligate requirement for diaminopimelic acid. The chromosomal Δasd mutation was complemented by a plasmid vector possessing theasd + gene. A portion of thepspA gene fromStreptococcus pneumoniae Rx1 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 recombinantSalmonella strain induced significant anti-PspA immunoglobulin G titers in serum and vaginal secretions. Polyclonal sera from orally immunized mice detected PspA on theS. pneumoniae cell surface as revealed by immunofluorescence. Oral immunization of BALB/cJ mice with the PspA-producingSalmonella strain elicited antibody to PspA and resistance to challenge by the mouse-virulent human clinical isolateS. pneumoniae WU2. Immune sera from orally immunized mice conferred passive protection against otherwise lethal intraperitoneal or intravascular challenge with strain WU2.

infection and immunity

A Live Recombinant Avirulent Oral <i>Salmonella</i> Vaccine Expressing Pneumococcal Surface Protein A Induces Protective Responses against <i>Streptococcus pneumoniae</i>

A Live Recombinant Avirulent Oral Salmonella Vaccine Expressing Pneumococcal Surface Protein A Induces Protective Responses against Streptococcus pneumoniae