Murine intranasal challenge model for the study of Campylobacter pathogenesis and immunity.

Campylobacter jejuni infection of mice initiated by intranasal administration was investigated as a potential model for studies of pathogenesis and immunity. By using a standard challenge (5 x 10(9) CFU), C. jejuni 81-176 was more virulent for BALB/c (72% mortality) than for C3H/Hej (50%), CBA/CAJ (30%), or C58/J (0%). Intranasal challenge of BALB/c was used to compare the relative virulence of three reference strains; C.jejuni 81-176 was more virulent (killing 83% of challenged mice) than C. jejuni HC (0%) or C. coli VC-167 (0%). The course of intranasally initiated C. jejuni 81-176 infection in BALB/c was determined. C. jejuni was recovered from the lungs, intestinal tract, liver, and spleen at 4 h after challenge, the first interval evaluated. After this initial interval, three distinct patterns of infection were recognized: (i) a progressive decline in number of C. jejuni CFU (stomach, blood, lungs), (ii) decline followed by a second peak in the number of organisms recovered at 2 or 3 days postchallenge (intestine, liver, mesenteric lymph nodes), and (iii) persistence of approximately the same number of C.jejuni CFU during the course of the experiment (spleen). Intranasally induced infection initiated with a sublethal number of bacteria or intranasal immunization with killed Campylobacter preparations resulted in both the generation of Campylobacter antigen-specific immune responses and an acquired resistance to homologous rechallenge. The model was used to evaluate the relative virulence of nine low-in vitro-passage (no more than five passages) isolates of C. jejuni species from patients with diarrhea. The patient isolates were differentially virulent for mice; one killed all exposed mice, three were avirulent (no deaths) and the remainder showed an intermediate virulence, killing 17 to 33%. Mouse virulence of Campylobacter strains showed a trend toward isolates originating from individuals with watery diarrhea; however, no association was found between mouse virulence and other signs or symptoms. There were no observed relationships between mouse virulence and bacterial Lior serotype or Fla polymorphic group. Intranasal challenge of BALB/c with C. jejuni is a useful model for the study of infection and vaccination-acquired immunity to this agent.

Immunogenicity and protective efficacy of a prototype Campylobacter killed whole-cell vaccine in mice.

The immunogenicity and efficacy of an experimental inactivated Campylobacter jejuni whole-cell (CWC) vaccine were evaluated in mice. Mice were orally immunized in a three-dose primary series (48-h intervals) at doses of 10(5), 10(7), or 10(9) CWC vaccine particles alone or in combination with 25 micrograms of a mucosal adjuvant, the heat-labile enterotoxin of Escherichia coli (LT). The comparative immunogenicities of both formulations were assessed on the basis of the generation of antigen-specific antibodies in serum and intestinal secretions, and efficacy was determined by measuring the degrees of protection afforded against intestinal colonization and systemic dissemination of challenge organisms. Campylobacter-specific intestinal immunoglobulin (Ig) A responses were dependent on the use of LT, whereas IgA and IgG responses in serum were not. Colonization resistance was induced over a broad range of vaccine doses when LT was included. However, only the highest dose of CWC alone gave comparable levels of protection. Both formulations provided equivalent protection against systemic spread of challenge organisms. These results indicate that both whole-cell vaccine formulations deserve further evaluation as candidate vaccines and also highlight the potential value of mucosal adjuvants, like LT, in enteric vaccine development.