Local immune response and protection in the guinea pig keratoconjunctivitis model following immunization with Shigella vaccines

Abstract

This study used the guinea pig keratoconjunctivitis model to examine the importance of route of administration (mucosal versus parenteral), frequency and timing of immunization (primary versus boosting immunization), and form of antigen given (live attenuated vaccine strain versus 0-antigen-protein conjugate) on the production of protective immunity against Shigella infection. Since local immune response to the lipopolysaccharide (LPS) 0-antigen of Shigella spp. is thought to be important for protection against disease, 0-antigenspecific antibody-secreting cells (ASC) in the spleen and regional lymph nodes of immunized animals were measured by using an ELISPOT assay. Results indicated that protective efficacy was associated with a strong 0-antigen-specific ASC response, particularly in the superficial ventral cervical lymph nodes draining the conjunctivae. In naive animals, a strong ASC response in the cervical lymph nodes and protection against challenge were detected only in animals that received a mucosal immunization. Protection in these animals was increased by a boosting mucosal immunization. While parenteral immunization alone with an 0-antigenprotein conjugate vaccine did not protect naive animals against challenge, a combined parenteral-mucosal regimen elicited enhanced protection without the addition of a boosting immunization. Although 0-antigenspecific serum immunoglobulin A titers were significantly higher in animals receiving a mucosal immunization, there was no apparent correlation between levels of serum antibody and protection against disease.

Immune Responses in Mice After Gastric and Subcutaneous Immunization with BCG

“…Similarly, Ogawa et al found that subcutaneous immunization of mice with fimbrial protein of Porphyromonas gingivalis induced systemic IgM and IgG responses, while oral immunization augmented all Ig responses as well as antigen-specific IgA responses in mucosa-associated lymphoid tissues [29]. Mucosal immunization with a live attenuated aro D-deleted Escherichia coli-Shigella flexineri 2a hybrid vaccine protected guinea-pigs against a S. fleineri challenge, while parenteral immunization with the vaccine did not [30]. Thus, such mucosal immunizations can sometimes induce protection to disease more effectively than systemic immunizations.…”

Construction of a Stable Attenuated Shigella sonnei Δ virG Vaccine Strain, WRSS1, and Protective Efficacy and Immunogenicity in the Guinea Pig Keratoconjunctivitis Model

“…Four guinea pigs were inoculated with 4 ϫ 10 8 CFU of the attenuated WRSS1 strain, and two guinea pigs were inoculated with 4 ϫ 10 8 of the parent wild-type S. sonnei Mosely strain, and development of disease was monitored for 5 days. The following rating scheme for development of disease was used: 0, no disease or mild irritation; 1, mild conjunctivitis; 2, keratoconjunctivitis with no purulence; 3, fully developed keratoconjunctivitis with purulence (15,16). Guinea pigs infected ocularly with 4 ϫ 10 8 CFU of the…”

“…The protective efficacy and immunogenicity of WRSS1 were measured with the guinea pig keratoconjunctivitis model (15,16). Ocular immunization with 3 ϫ 10 8 to 4 ϫ 10 8 CFU of WRSS1/eye on days 0 and 14 was followed by challenge with virulent S. sonnei.…”

“…Ocular immunization with 3 ϫ 10 8 to 4 ϫ 10 8 CFU of WRSS1/eye on days 0 and 14 was followed by challenge with virulent S. sonnei. The immunizing inoculum was obtained from overnight growth plates (experiment 1) as previously described (2,15,16) or from rehydration of lyophilized product manufactured at the Walter Reed Army Institute of Research pilot vaccine production facility with Good Manufacturing Procedures (GMP) (experiment 2). Four weeks after the last immunization, both the immunized animals and the unimmunized control animals were challenged with 4 ϫ 10 8 CFU of virulent S. sonnei 53G/eye.…”

Specificity of monoclonal antibodies elicited by mucosal infection of BALB/c mice with virulent Shigella flexneri 2a

“…3, 1996 NOTES 587 present study and the serum cross-reactivity found in humans and animals immunized or infected with serotype 2a (33) suggest that an S. flexneri 2a vaccine might also protect against other serotypes expressing the 3,4 group antigen. Data from studies that have used the guinea pig keratoconjunctivitis model (14,15,28) have demonstrated that infection with a serotype 2a strain can protect against challenge with a virulent Y strain (12). Further studies on the cross-reactivities of monoclonal antibodies and the serum antibody responses of animals and humans generated by immunization or infection by a mu-cosal route can determine other potential cross-reactivity patterns that might be useful in designing a multivalent vaccine.…”