Placebo-controlled double-blind clinical studies on the efficacy of different influenza vaccines assessed by experimental and natural infection

Abstract

SummaryFour placebo-controlled double-blind studies on the protective efficacies of a freeze-dried aerosol and an injectable whole-virion inactivated influenza vaccine, each containing 400 i.u. A/Port Chalmers/1/73 (H3N2) and 240 i.u. B/Hong Kong/8/73 per dose, were carried out on a total of 601 subjects using three different live influenza vaccines as challenge virus. In the second of these studies a tween-ether 'split' aluminium-absorbed injectable vaccine containing 400 CCA units A/Port Chalmers/1/73 (H,N2) and 300 CCA (chick cell agglutination) units B/Hong Kong/8/73 was also tested. Challenge in the first three studies occurred 3 weeks after vaccination whereas in the last study it took place 3 months after vaccination. In a placebo-controlled double-blind field trial conducted in parallel on 1326 subjects in the same population as the last challenge study, the aerosol vaccine gave 63%4 (P = 0-09) and the whole-virion vaccine only 35°4 (P = 0 37) protection against serologically confirmed influenza.It is concluded that challenge studies using a live vaccine as challenge virus can yield statistically significant results and that the efficacy of inactivated vaccines can be validly compared if they are adminiistered by the same route. Such studies can be conveniently conducted on large numbers of subjects and this method of assessing vaccine efficacy deserves to be further evaluated.