Induction of Immunity in Man by Crystalline Adenovirus Type 5 Capsid Antigens

Previous studies in animals and man have shown that adenoviral capsid proteins, hexon and fiber, possess immunologically unrelated antigenic determinants capable of inducing neutralizing antibody (1–4). Also, a protective effect of antibody stimulated by both antigens was suggested by resistance of vaccinated adult volunteers to experimental infection. However, the use of adenoviral capsid antigens as vaccines for prevention of adenoviral disease has not been attempted primarily because of the inability to consistently prepare vaccines with an acceptable potency and degree of purity. The recent demonstration of crystallization of adenoviral proteins now provides an additional procedure for purification and allows for further studies in man with preparations that have important attributes (5, 6). Since dosage can be specified in μg of protein, standardization and reproducibility of vaccines is assured. Such vaccines are free of adventitial proteins and thus may be less reactogenic and, as only the desired antibody response is obtained, they may be less prone to induce potentially harmful sensitization. Moreover, they are free of nucleic acid and thus presumably free of any tumorigenic potential. Finally, preparations of different serotypes may be used as polyvalent antigen preparations, an attribute desirable for immunization against adenoviral disease, particularly for pediatric age groups. In the present study, crystalline hexon and fiber proteins of type 5 adenovirus were given to adult volunteers. Low reactogenicity was observed, a significant frequency of serum antibody responses occurred, and vaccinated volunteers exhibited resistance to challenge with live adenovirus type 5. Materials and Methods. Vaccine Preparation. A nonprototype strain of adenovirus type 5 was isolated from a throat specimen obtained from a seventeen-month-old child. The clinical specimen was kindly provided by Dr. Albert Kapikian of the National Institute of Allergy and infectious Diseases.