Secretory IgA antibodies in mucosa are known to play an essential role in protection against various infectious agents. To enhance the induction of protective mucosal
antibodies,
influenza HA
vaccine was inoculated intranasally into mice with the B subunit of
cholera toxin (CTB), which is known to be an excellent mucosal self-adjuvanting molecule. This combination resulted in high levels of
antiviral IgA antibodies in nasal secretions and enhanced serum haemagglutinin-inhibiting (HI)
antibodies 4 weeks after inoculation, compared with the inoculation of
vaccine alone which induced only a low level of HI serum
antibodies and no local
IgA antibodies. (Subcutaneous or intraperitoneal inoculation of the
vaccine with CTB failed to induce detectable nasal
antiviral IgA antibodies). Levels of nasal
IgA and serum HI
antibodies increased in a dose-dependent fashion with increasing nasal doses of both
vaccine and CTB, and correlated with the degree of protection against viral challenge. A greater protective effect was seen with
cholera toxin than with its B subunit. Moreover, a second administration of
vaccine alone, 4 weeks after the inoculation of the
vaccine with CTB, elevated the level of the
antiviral IgA nasal
antibodies to 10-100 times higher than that of the primary response. These results suggest that either CT or CTB could be used as a potent adjuvant to induce protective secretory
antibodies by nasal vaccination against pathogens impinging on respiratory mucosa.