Effects of frequent intranasal administration of adjuvant-combined influenza vaccine on the protection against virus infection.
In previous papers, we have shown that Escherichia coli heat-labile enterotoxin B subunit, supplemented with a trace amount of the holotoxin (LTB*) could be used as a potent adjuvant for a nasal influenza HA (haemagglutinin) vaccine in humans. The present study was designed to determine whether the effectiveness of a combined LTB*-HA vaccine could be limited by preexisting immunity to LTB and how many times the adjuvant-combined vaccine could be administered intranasally without reducing its protective efficacy in BALB/c, C3H and B10 mice. The magnitude of both nasal and serum Ab responses to HA vaccine was correlated with the degree of protection against virus infection. Higher doses of LTB*-combined vaccine were required for inducing high enough levels of anti-HA Ab responses to provide complete protection in low responder mice. Repeated pretreatments with LTB* alone (more than six times), which provided high levels of preexisting Abs to LTB, inhibited the induction of anti-HA Ab responses and reduced the protective efficacy of the adjuvant-combined vaccine. However, the LTB*-combined vaccine could be given repeatedly (about ten times) to mice without reducing the effectiveness of the adjuvant-combined vaccine. These results suggest that the LTB*-combined nasal influenza vaccine can be given to humans once every few years when an epidemic of influenza may occur.
Tamura
S
S
Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
Yajima
A
A
Hatori
E
E
Tamura
S
S
Asanuma
H
H
Suzuki
Y
Y
Aizawa
C
C
Kurata
T
T
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000281:Administration, Intranasal; D000818:Animals; D001427:Bacterial Toxins / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology; D029968:Escherichia coli Proteins; D005260:Female; D006183:H-2 Antigens / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000627:therapeutic use*
D000276:Adjuvants, Immunologic; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D006183:H-2 Antigens; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D017778:Vaccines, Combined; C027538:heat-labile enterotoxin, E coli