Advances in DNA vaccines

Nurse Practitioner, Jan 2002 by Simmerman, James Mark

DNA Vaccine Advantages

In approximately 10 years, DNA vaccines have progressed from theory to reality. Also called nucleic acid or genetic vaccination, DNA vaccines include several advantages (see Table 3): They are easy to produce in the laboratory; relatively inexpensive; less sensitive to heat than live vaccines; and not susceptible to reversion. They also may be safer in immunocompromised patients, and their use circumvents the problem of protein purification common to recombinant, protein-based vaccines.18,19

DNA vaccines are effective in small (nanogram) quantities with or without adjuvants20,21 and can be administered orally, epidermally, mucosally (oral, intranasal, vaginal), intramuscularly, and intravenously.22-24 With DNA vaccines, vaccinologists can control the type of antigen produced and how it will be presented to the host immune cells. Consequently, researchers can tailor DNA vaccines for specific purposes.

How DNA Vaccines Work

DNA vaccines work by introducing genes into host cells that encode for an antigenic protein. These transfected host cells then manufacture the foreign protein themselves, inducing an immune response. DNA vaccines can contain one or more genes that encode for an antigenic epitope such as a virus envelope protein. When presented to the immune system, an APC may transfect the gene, particularly certain B cells and dendrocytes. Then, T cells or somatic cells (muscle, skin, membranes) may be directly transfected with the gene, encoding for the foreign protein.14,25 Transfected host cells begin to manufacture small quantities (picograms) of the foreign protein, eliciting humoral and CMI responses.

Researchers can deliver the DNA vaccine gene, which is also called a transgene, in various ways. Naked DNA can be injected intramuscularly in a saline solution, attached to microscopic gold or tungsten beads and pushed into the skin with a helium blast (gene gun), or incorporated into live, highly attenuated, nonpathogenic viruses or bacteria that carry the transgene to host immune cells.26,27 Using bacteria or viruses that replicate but do not cause disease in human cells as DNA vectors may amplify immune response and increase vaccine effectiveness.18,19,28

Although numerous studies have demonstrated DNA vaccines' immunogenicity, experimental DNA vaccines do not always confer complete protection from highly pathogenic organisms. Vaccinologists are researching ways to increase the immune response through novel vectors, new adjuvants, and combination vaccination strategies.

The Prime-Boost Strategy

The prime-boost strategy involves priming with a DNA vaccine and then boosting with a subunit peptide vaccine or a recombinant protein vaccine. The prime-boost approach seems to consistently improve immune responses.29 In a recent study in nonhuman primates, the prime-boost strategy conferred protective immune responses against HIV-1 infection.30 In the future, clinicians may apply the prime-boost approach when vaccinating their patients.31