The Emerging Role of DNA Vaccines

W. Michael McDonnell, MD, Western Washington Medical Group, and Frederick K. Askari, MD, PhD, University of Michigan.

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In This Article

Problems with DNA Vaccines

There are many potential problems and unanswered questions concerning the use of DNA vaccines.[14] The possibility of insertional mutagenesis is a concern that needs to be more rigorously tested. While there is no evidence that the introduced DNA integrates into the host genome, if it were to occur, it would raise the specter of carcinogenesis; oncongenes may be turned on or tumor suppressor genes inhibited. What if DNA circulated throughout the body after injection and integrated into germ cells? Might subsequent generations express the antigen from birth and develop tolerance, instead of immunity, to the pathogen? Anti-DNA antibody formation and the possibility of autoimmune diseases is another concern.

These are important issues because unlike other forms of gene therapy, which target very ill patients, DNA vaccines are targeted at the young and the healthy. If host cells express antigen for a prolonged period, what effect would that have on the immune response? Could it lead to host tolerance or an exaggerated, damaging attack on tissues expressing antigen? What is the exact nature of the gene transfer and antigen processing? While injections are given intramuscularly it may not be myocytes that are actually presenting antigens to T cells. What cells are taking up the gene? Initially it was thought that myocytes were expressing the DNA product and stimulating a cellular response, but further work indicates that dendritic cells found throughout the body (except in the brain) may be the antigen presenting cells.[1] Because there is a brisk humoral response, it seems that some vaccine product is being delivered to B cells, macrophages or other MHC class II cells.[3]

The Food and Drug Administration has recently published a document entitled Points to Consider on Plasmid DNA Vaccines for Preventive Infectious Disease, to help researchers and manufacturers understand the safety concerns involved with their approval of DNA vaccines for phase I human trials.

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