Vaccines are widely recognized as the most cost-effective healthcare approach to combating infectious diseases. So why is there no vaccine against one of the leading infectious causes of birth defects in the United States, cytomegalovirus (CMV)? The development of effective vaccines for CMV and many other diseases has been challenging in large part because of some inherent limitations of the major conventional vaccine approaches.
Vaccines work by giving the immune system a “sneak preview” of an infectious organism to produce T-cells (think of them as the “Green Berets” of the immune system) and antibodies (the “cruise missiles” of the immune system) against its specific features. The three major conventional vaccine approaches are to use live but weakened (live-attenuated) viruses or bacteria; whole killed pathogens; or a piece of the target pathogen (subunit vaccine). There are pros and cons to each approach but ultimately none seems to be enough to combat CMV.
Although the subunit and the killed vaccines are relatively safe, these approaches induce predominantly an antibody “cruise missile” immune response, which typically is not fully effective against a persistent organism such as CMV which hides within living cells.
Although the vaccines that use the live-attenuated approach are very likely to successfully produce the desired T-cell “Green Berets,” which appear to be an important component of a fully effective immune response against CMV, these vaccines contain live viruses that carry a risk of causing the disease they are designed to prevent. In addition, development of live-attenuated vaccines requires significant time and investment in research and manufacturing. This information may seem discouraging to many people but a novel approach to vaccination provides renewed hope for an effective CMV vaccine. Gene-based vaccines, either delivered by another virus or in rings of DNA called plasmids, use portions of the genetic code of the bacteria or virus from which a disease originates to cause the host to produce proteins of the bacteria or virus that may induce an immune response.
This method, particularly the plasmid-DNA approach, potentially offers superior safety, ease and reliability of manufacturing, as well as convenient storage and handling characteristics, compared with conventional vaccines. DNA vaccines have the potential to induce potent T-cell “Green Beret” responses against target pathogens and trigger production of antibodies.
Over the past decade, hundreds of scientific publications have documented the effectiveness of DNA vaccines in dozens of species. The first regulatory approvals of DNA vaccines occurred in July 2005, with back-to-back approvals of vaccines against West Nile virus in horses and against a deadly virus (Haematopoietic Necrosis virus) in farm-raised salmon.
Vical Incorporated, a San Diego-based biotech company, launched a development program for a DNA vaccine against CMV in 2003 and already has advanced through Phase One clinical testing. A Phase Two trial is expected to begin in early 2006. The initial focus is on transplant patients, who are at high risk of CMV disease, which should allow demonstration of effectiveness in a small trial. Success with people who have undergone an organ transplant could then lead to the opportunity to develop a CMV vaccine to protect infants from CMV disease acquired before birth.
Additional information on Vical is available at www.vical.com.
Alan R. Engbring is executive director of Investor Relations at Vical Incorporated. He has more than 20 years of experience as a corporate communications professional. Mr. Engbring received his B.A. in journalism from Marquette University and his M.B.A. from Northern Illinois University.
