Intranasal booster vaccination against diphtheria and tetanus in man

Vaccine. 1997 Feb;15(3):307-16. doi: 10.1016/s0264-410x(96)00175-2.


The booster responses of three different formulations of intranasal (i.n.) diphtheria-tetanus (D-T) vaccines were determined in military recruits and compared with a conventional subcutaneous D-T vaccine. The vaccines for mucosal delivery were sprayed into one nostril and contained D and T toxoids in an enhancer mixture of polysorbate and caprylic/capric glycerides. All of the vaccines gave rise mainly to a systemic IgG response. Among 51 persons with anti-D antibody concentrations in serum below a protective level of 0.01 international units (IU ml-1) before vaccination, all except two attained protective antibody concentrations 4 weeks after vaccination. The median increase in anti-D antibody concentration was 113-fold with the most efficient i.n. formulation. The median increase in anti-T antibody level was 2.4-fold, however, the pre-vaccination levels for this antigen were very high. Within the examined levels, the booster response depended mainly on the dose of the antigen in the vaccine rather than on the concentration of the vehicle mixture. Compared with the parenteral D-T vaccine containing aluminium hydroxide as an adjuvant, all of the tested i.n. formulations showed somewhat lower immunogenicity in man as well as in pre-clinical guinea-pig studies. Among 215 persons immunized i.n., 61% preferred this route of administration rather than a parenteral injection, although the formulations were all associated with varying local symptoms, frequently stinging and pronounced, nasal secretion.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Comparative Study

MeSH terms

  • Administration, Intranasal
  • Adolescent
  • Adult
  • Animals
  • Antibodies, Bacterial / biosynthesis
  • Diphtheria Toxoid / administration & dosage*
  • Diphtheria Toxoid / adverse effects
  • Diphtheria Toxoid / immunology*
  • Diphtheria-Tetanus Vaccine
  • Female
  • Guinea Pigs
  • Humans
  • Immunization Programs
  • Immunization, Secondary / adverse effects
  • Immunization, Secondary / methods*
  • Injections, Subcutaneous
  • Male
  • Tetanus Toxoid / administration & dosage*
  • Tetanus Toxoid / adverse effects
  • Tetanus Toxoid / immunology*
  • Vaccines, Combined / administration & dosage
  • Vaccines, Combined / adverse effects
  • Vaccines, Combined / immunology


  • Antibodies, Bacterial
  • Diphtheria Toxoid
  • Diphtheria-Tetanus Vaccine
  • Tetanus Toxoid
  • Vaccines, Combined