Efficacy of nasal influenza vaccine combined with Escherichia coli heat-labile enterotoxin B subunit containing a trace amount of the holotoxin in healthy volunteers

Abstract

We conducted a field trial to evaluate the efficacy of nasal influenza vaccine combined with Escherichia coli heat-labile enterotoxin B subunit (LTB) containing a trace amount of the holotoxin (LT) in preventing or attenuating influenza among volunteers during the winter season of 1994-1995. A trivalent inactivated influenza vaccine, composed of A/Yamagata/32/89 (H1N1), A/Kitakyusyu/159/93 (H2N2) and B/Mie/1/93 influenza virus strains, was administered intranasally together with recombinant LTB containing 1% recombinant LT (LTB*). Vaccination was done twice 4 weeks apart. Salivary secretory IgA and serum HI antibodies were measured before and 8 weeks after the primary vaccination. Thirty-two volunteers were enrolled in this study; 18 volunteers (mean age 37.7 +/- 11.3) were given LTB*-combined vaccine and 14 volunteers (mean age 44.1 +/- 11.3) given placebo. Outbreaks of H3N2 subtype and B type virus were observed during this study period. Six (42.9%) of the 14 volunteers in the placebo group and 3 (16.7%) of the 18 receiving the LTB*-combined vaccine contracted influenza. There was no statistically significant difference between the two groups, because the number of subjects was small. Higher percentage of positive IgA and HI antibody responses among vaccines given vaccine with LTB* were observed as compared with those in the placebo group. Positive IgA antibody response to all vaccine strains were observed in 46.7% (7/15) of the vaccine group. On the other hand, none of the placebo group showed positive IgA antibody response to all vaccine strains. These results suggest that nasal influenza vaccine with LTB* appears to be effective in preventing influenza.