holothurin and Influenza--Human

Escherichia coli heat-labile enterotoxin B subunit (LTB) (2 micrograms), supplemented with a trace amount of the holotoxin (LT) (0.02-20 ng), was examined for the adjuvant effect on antibody (Ab) responses against influenza inactivated haemagglutinin (HA) vaccine in Balb/c mice. Each mouse received a primary intranasal (i.n.) inoculation with the vaccine (1.5 micrograms), prepared from PR8 (H1N1) virus, together with LT-containing LTB and in 4 weeks a second i.n. inoculation of the vaccine alone. The inoculation of the vaccine with the LT-containing LTB induced significantly high primary and secondary anti-HA IgA and IgG Ab responses in the nasal wash and the serum, while the vaccine with LTB or less than 2 ng of LT induced little response. The synergistic adjuvant effect was maximal in the concentration of LTB supplemented with 0.2-2 ng of LT. Under these conditions, the augmented IgA and IgG Ab responses, which are cross-protective to PR8 HA molecules, provided complete cross-protection against PR8 virus challenge in mice immunized with heterologous vaccine within the same subtype. These results suggest that LTB containing a trace amount of LT can be used as a potent adjuvant for nasal vaccination of humans against influenza.

Topics: Adjuvants, Immunologic; Administration, Intranasal; Animals; Antibodies, Viral; Bacterial Toxins; Dose-Response Relationship, Immunologic; Drug Synergism; Enterotoxins; Enzyme-Linked Immunosorbent Assay; Escherichia coli; Escherichia coli Proteins; Female; Glycosides; Hemagglutinin Glycoproteins, Influenza Virus; Hemagglutinins, Viral; Holothurin; Humans; Immunoglobulin A; Immunoglobulin G; Influenza Vaccines; Influenza, Human; Mice; Mice, Inbred BALB C; Orthomyxoviridae; Recombinant Proteins; Sea Cucumbers; Triterpenes