Immunity against Campylobacter jejuni, a major food-borne pathogen causing diarrhea, is largely serotype specific. The major outer membrane protein (MOMP) of C. jejuni, PorA, is a common antigen with the potential to provide broad protection. Adult BALB/c mice were orally immunized with a recombinant glutathione S-transferase (GST) fused to PorA prepared from Campylobacter jejuni C31 (O:6,7) (GST-PorA) combined with a modified heat-labile enterotoxin of Escherichia coli as an adjuvant and later orally challenged with C31 strain or three heterologous strains: 48 (O:19), 75 (O:3), and 111 (O:1,44). Protection from colonization with the challenge organism was studied by fecal screening daily for 9 days. Serum and intestinal lavage fluid antibodies against the vaccine and Sarkosyl-purified MOMP from C31 were measured by using an enzyme-linked immunosorbent assay. The vaccine produced robust antibody responses against both antigens in serum and secretion. Since strain C31 was a poor colonizer, homologous protection could not be studied. The protective efficacies of heterologous strains were 43% (for strain 48, P < 0.001), 29% (for strain 75, P < 0.005), and 42% (for strain 111, P < 0.001) for the 9-day period compared to control mice given phosphate-buffered saline. Thus, PorA provided appreciable protection against colonization with heterologous serotypes.Campylobacter jejuni is a food-borne pathogen and a leading cause of diarrhea worldwide (19,33,34). Campylobacteriosis is associated with a number of important sequelae, including Guillain-Barre syndrome, Reiter's syndrome, reactive arthritis, and irritable bowel syndrome (10, 37). C. jejuni also contributes to significant mortality of children in developing countries (18). In view of significant morbidity, mortality, and economic burden associated with C. jejuni infection, the control and prevention of campylobacteriosis are a priority. One possible tool for the prevention of campylobacteriosis is vaccination. It has been observed that C. jejuni infection results in the acquisition of immunity. However, immunity in humans seems to be serotype (Penner serotype) specific (13, 36). There are numerous serotypes of C. jejuni according to the Penner serotyping scheme, which is based on the lipopolysaccharide capsule (25). Therefore, vaccines based on common antigens that are shared by all serotypes seem attractive for broad protection. One such antigen is the major outer membrane protein (MOMP) of C. jejuni, PorA, which is present in abundant quantity in the organism. There are three conformational forms of MOMP: folded monomer (35 kDa), denatured monomer (45 kDa), and the native trimer (120 to 140 kDa). Only the folded monomer and the native trimer have pore-forming activities (44). The MOMP is involved in ion transport across the bacterial cell wall and adhesion of the bacterium to the intestinal mucosa (30, 41). It consists of 18 -strands connected by short periplasmic turns and nine external loops. The external loops are antigenically variable (44). This is evident...