Saliva, breast milk, and serum antibody responses as indirect measures of intestinal immunity after oral cholera vaccination or natural disease

Abstract

The possibility that antibody responses in serum, saliva, or breast milk samples to oral vaccines or enteric infections may reflect the intestinal immune response was evaluated in Bangladeshi volunteers orally immunized with a cholera B subunit-whole-cell vaccine (B+WCV) and in patients convalescing from enterotoxin-induced diarrheal disease. Two peroral doses of B+WVC induced antitoxin and antibacterial antibody responses in the intestinal fluids of 76 and 92%, respectively, of the volunteers and in serum samples in 90 and 69% of those tested. These responses were comparable to those obtained after cholera or enterotoxigenic Escherichia coli disease. Whereas immunoglobulin A (IgA) antitoxin titer increases in saliva (44%) and breast milk (29%) specimens after vaccination were less frequent than in intestinal fluid (76%), antitoxin responses in saliva and breast milk occurred in 80 to 90% of the patients after disease. Also, antilipopolysaccharide (anti-LPS) titer increases in extraintestinal body fluids were found more frequently after disease than after vaccination. A comparison of the frequency and magnitude of antibody response in different body fluids with those in intestinal lavage fluid revealed no extraintestinal antibody that directly reflected the intestinal immunity. However, comparison of vibriocidal and IgG antitoxin antibodies in serum specimens with antitoxin and anti-LPS IgA responses in intestinal fluids after the vaccination of volunteers showed a sensitivity of 70 to 90% and a predictive accuracy of about 80% for the serum analyses reflecting the intestinal immune responses. Furthermore, antitoxin and anti-LPS antibody responses in saliva and breast milk samples seemed to be useful proxy indicators of a gut mucosal response of these antibodies after enterotoxin-induced diarrheal disease showing sensitivity values of 70 to 90% and predictive accuracy values of 70 to 100%.