INDUCTION OF PROTECTIVE IMMUNITY AGAINST INFLUENZA-VIRUS IN A MACAQUEMODEL - COMPARISON OF CONVENTIONAL AND ISCOM VACCINES

Cynomolgus macaque monkeys (Macaca fascicularis) were immunized twice intramuscularly, either with a conventional non-adjuvanted subunit vac cine or with a candidate immune-stimulating complex (iscom) vaccine, e ach containing 10 mu g envelope glycoprotein of a recent human influen za A(H3N2) virus (A/Netherlands/18/94). In contrast to the macaques va ccinated with the classical subunit vaccine, those immunized with the iscom vaccine developed high titres of specific IgM, IgA and IgG serum antibodies, as well as high titres of haemagglutination-inhibiting an d virus-neutralizing serum antibodies. Also, specific proliferative T cell responses were only found in the iscom-vaccinated monkeys and the ir levels were similar to those found in monkeys experimentally infect ed with the homologous virus. Upon intratracheal challenge with the ho mologous virus, the iscom-vaccinated monkeys were completely protected from detectable virus replication in lungs, pharynx and nose, whereas those vaccinated with the classical subunit vaccines were not, or wer e only partially protected. The kinetics of specific serum antibody de velopment in the iscom-vaccinated monkeys after challenge were quite s imilar to those of monkeys after secondary infection with the same vir us. In contrast, the post-challenge kinetics of serum antibody develop ment in the monkeys vaccinated with the classical subunit vaccines res embled those of naive monkeys, confirming that these vaccines only pro vided limited protection in such animals.