Estimation of the effective doses of nasal-inactivated influenza vaccine in humans from mouse-model experiments.
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*.
Tamura
Shin-ichi
S
Department of Pathology, National Institute of Infectious Diseases, Musashimurayama, Tokyo, Japan. sintam41@nn.em-net.ne.jp
Hasegawa
Hideki
H
Kurata
Takeshi
T
D000281:Administration, Intranasal; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D051379:Mice; D057170:Translational Research, Biomedical; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology
D007252:Influenza Vaccines; D015164:Vaccines, Inactivated