Effect of dosage and route of inoculation upon antigenicity of inactivated influenza virus vaccine (Hong Kong strain) in man.

Earlier studies on the antibody response to inactivated influenza vaccines injected by different routes have given contradictory results, some suggesting that 0.1 ml intradermally is superior to 1.0 ml subcutaneously, others suggesting the opposite. With the advent of the 1968-69 Hong Kong influenza epidemic it seemed worth while to re-evaluate whether a smaller intradermal dose would elicit antibody responses comparable to those following a larger subcutaneous dose.A study was performed evaluating 3 doses: 0.1 ml (65 CCA), 0.25 ml (160 CCA), and 0.5 ml (320 CCA) of zonal-purified vaccine. The 0.1-ml dose was administered by both routes, and the other doses subcutaneously only. The effect of "booster" inoculation by the same route 2 and 4 weeks later was also studied. Sera were examined for haemagglutination-inhibiting antibody, and antibody response was determined by the percentage showing 4-fold or greater titre rises and by increase in geometric mean titre.The antibody response to the first inoculation was highest in the 0.1-ml intradermal groups and the lowest in the 0.1-ml subcutaneous groups. All groups receiving a second inoculation 2 weeks after the first experienced an increase in antibody response; responses to the second inoculation given 4 weeks after the first were variable. Considering the over-all effect of all combinations of doses and routes, the intradermal groups appeared to achieve the best antibody response and the 0.1-ml subcutaneous groups the least.There appeared to be an inverse relationship between antibody response and pre-immunization antibody titre.The data show that, with vaccine of similar CCA content, 0.1 ml intradermally would be a reasonable alternative to, and perhaps better than, the usual 0.5-ml subcutaneous dose. The limitations of this approach are discussed.