Live Recombinant Adenovirus Vaccine Technique Explored

March 15, 2005

Research Could One Day Lead to More Economical Vaccines

Researchers at the Johns Hopkins Bloomberg School of Public Health are exploring ways to develop new vaccines for a variety of illnesses using genetically modified adenoviruses, a common cause of respiratory infections. Oral adenovirus vaccines have long been proven to be safe and effective. The researchers believe their process for constructing a replicating live recombinant adenovirus could lead to more economical vaccines that provide longer-lasting disease protection, which would be particularly beneficial for people living in the developing countries where resources are limited. Their research was made available online March 14, 2005, in advance of publication in the Proceedings of the National Academy of Sciences.

“Many vaccines are expensive to manufacture, require trained personnel to administer and multiple doses to provide immunity, which is not feasible for people living in many parts of the world,” explained Gary Ketner, PhD, senior author of the study and professor with the W. Harry Feinstone Department of Molecular Microbiology and Immunology at the Bloomberg School of Public Health. “The military developed oral vaccines for adenovirus years ago that safely provide immunity in one dose. We wanted to see if we could combine the safe and easy-to-use qualities of live adenovirus vaccine with the versatility of recombinant adenovirus virus vaccines that are being developed.”

Specifically, Dr. Ketner and his colleagues hope to develop a vaccine for human papillomavirus (HPV) that could be used in the developing world. HPV causes 500,000 cases of cervical cancer each year worldwide. Recombinant HPV vaccines currently in clinical trials may not be ideal in poorer countries because they are expensive and require multiple immunizations.

The Hopkins researchers developed their vaccine prototype using canine oral papillomavirus (COPV), which behaves similarly to HPV. Research by other scientists showed that a vaccine consisting of recombinant HPV major capsid protein (L1) provides effective immunity to HPV infection. Dr. Ketner and his colleagues theorized that a live recombinant adenovirus could be made to express L1 as the virus replicated in the body and thereby create a lasting immune response. The researchers inserted the L1 gene into a live adenovirus such that it would be expressed using the virus' own late-gene expression machinery. L1 is expressed at very high levels in some recombinants.

Dr. Ketner believes that the replicating live recombinant adenovirus model shows promise as a means of developing economical and long-lasting vaccines for many illnesses. Ongoing research is aimed at determining the effectiveness of recombinants in animals.

Additional authors of “Viable adenovirus vaccine prototypes: High-level production of a papillomavirus capsid antigen from the major late transcriptional unit” include Michael Berg, Julie DiFatta and Egbert Hoiczyk of the W. Harry Feinstone Department of Molecular Microbiology and Immunology at the Johns Hopkins Bloomberg School of Public Health. Author Richard Schlegel is with the Department of Pathology at the Georgetown University Medical Center.

Funding was provided by grants from the National Institutes of Health.