Estimation of the effective doses of nasal-inactivated influenza vaccine in humans from mouse-model experiments

Jpn J Infect Dis. 2010 Jan;63(1):8-15.

Abstract

Mouse models of influenza play an important role in developing effective human influenza vaccines. We have demonstrated that intranasal immunization with inactivated subvirion (SV) vaccines, in conjunction with a cholera toxin B subunit adjuvant (CTB*), provides more effective cross-protection than parenteral immunization in BALB/c mice. In addition, the minimal effective dose of nasal vaccine for providing complete protection against a lethal influenza virus infection is 0.1 microg SV vaccine (containing about 30 ng hemagglutinin [HA]) (with 0.1 microg CTB*) in BALB/c mice (20 g body weight) immunized twice intranasally 4 weeks apart. The effective dose in humans can be estimated to be roughly 100 microg SV vaccine (containing approximately 30 microg HA) (with 100 microg CTB*)/20 kg body weight by using the dose/body weight ratio from actual vaccination trials. This estimation can be rationalized by the hypothesis that the distribution of strains (or individuals) in a mouse (or human) population, in relation to their HA antigen responsiveness, follows a normal distribution, and by the fact that BALB/c mice are intermediate responders for anti-HA antibody responses, and correspond to human intermediate responders, which form the largest population. We also discuss the use of innate immune responses, as well as antibody responses, in BALB/c mice to assess the efficacy of unknown adjuvants and the development of other adjuvants for nasal vaccines that should be clinically safer than CTB*.

Publication types

  • Review

MeSH terms

  • Administration, Intranasal
  • Animals
  • Dose-Response Relationship, Drug
  • Humans
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / immunology*
  • Influenza, Human / prevention & control*
  • Mice
  • Translational Research, Biomedical*
  • Vaccines, Inactivated / administration & dosage
  • Vaccines, Inactivated / immunology

Substances

  • Influenza Vaccines
  • Vaccines, Inactivated