Strong biotype and serotype cross-protective antibacterial and antitoxic immunity in rabbits after cholera infection

We studied whether immunity evoked by infection with classical or El Tor V. cholerae 01 organisms in rabbits (the RITARD model) also gives protection against cholera caused by V. cholerae of heterologous biotype as well as serotype, and whether such protection is antibacterial and/or antitoxic. A primary infection with a classical Ogawa or El Tor Inaba strain resulted in intestinal colonization and diarrheal disease in a dose-related manner though the El Tor strain was more virulent. As few as 10(3) El Tor organisms gave disease in more than 90% of the rabbits as compared to 10(9) classical organisms (ED90); the El Tor strain also gave rise to diarrhea with earlier onset and of greater severity and longer duration. The primary infection induced strong protective immunity against later challenge with either the homologous or the heterologous strain in doses that corresponded to 1,000 x ED90. Protection was associated with marked inhibition of colonization, and when rabbits convalescing from cholera infection were challenged with graded doses of bacteria or purified toxin in ligated intestinal loops significant antibacterial as well as antitoxic immunity was evident. Titer rises in serum vibriocidal and anti-lipopolysaccharide antibodies were similar after infection with either strain, whilst antitoxin titer rises were more marked after El Tor infection. During infection V. cholerae 01 organisms seem to express protective antigens that stimulate immunity which extends across both biotype and serotype barriers.