SYNERGISTIC ACTION OF CHOLERA-TOXIN B SUBUNIT (AND ESCHERICHIA-COLI HEAT-LABILE TOXIN-B SUBUNIT) AND A TRACE AMOUNT OF CHOLERA WHOLE TOXIN AS AN ADJUVANT FOR NASAL INFLUENZA VACCINE

Cholera toxin B subunit (CTB) and Escherichia coli heat-labile toxin ( LTB) (2 mu g), each supplemented with a trace amount of cholera toxin (CT) (0.02-20 ng), were examined for the adjuvant effect on antibody ( Ab) response against influenza inactivated HA (haemagglutinin) vaccine in Balb/c mice. Each mouse received a primary intranasal (i.n.) inocu lation of the vaccine (1.5 mu g) and the CT-containing CTB and in 4 we eks a second i.n. inoculation of the vaccine alone. The primary inocul ation of the vaccine with CTB alone did not induce either anti-HA IgA or IgG Ab response, or haemagglutination-inhibition Ab responses in th e serum. The vaccine with less than 2 ng of CT also failed to induce A b response. On the other hand, the vaccine with CT-containing CTB indu ced a high Ab response, which increased depending on the CT dose. More over, the second vaccine induced a response more than ten times higher than the primary one and the response increased depending on the CT d ose. Similar enhancement was found in the local anti-HA IgA Ab respons e in the nasal wash. Such synergistic effects were observed also betwe en LTB and CT. The amount of Ab produced by the synergism was consider ed to be enough to protect against virus infection. These results sugg est that CTB (or LTB) containing a trace amount of CT (about 0.1%) can be used practically as a potent adjuvant for nasal vaccination of hum ans against influenza.