Intranasal DNA Vaccine for Protection against Respiratory Infectious Diseases: The Delivery Perspectives

Xu, Yingying; Yuen, Pak-Wai; Lam, Jenny Ka-Wing

Typically, DNA vaccines are administered by intramuscular injection although other administration routes including intradermal, subcutaneous, oral and intranasal routes are also investigated. Upon administration, somatic cells (e.g., myocytes or keratinocytes) and professional antigen presenting cells (APCs) are transfected. As the antigens are expressed intracellularly, both humoral and cell-mediated immunity can be activated to offer broad immune protection. The host-synthesized antigens become the subject of immune surveillance in the context of both major histocompatibility complexes (MHC) class I and class II molecules of APCs. Antigen expressed APCs then travel to the draining lymph nodes where they present the antigenic peptide-MHC complexes and stimulate T cells. Alternatively, B cells are activated, initiating the antibody production cascades. The major advantage of DNA vaccines is their ability to activate CD8 + T-cells, the cytotoxic T lymphocytes, which are important in controlling infections [17] . This action is lacking in inactivated or subunit vaccines. The induction of CD8 + T-cells by DNA vaccines can occur in two major ways: (i) direct DNA transfection of the APCs such as dendritic cells (DCs); (ii) cross-presentation which occurs when somatic cells such as myocytes are transfected with DNA and the expressed antigens are taken up by the APCs, or when the transfected apoptotic cells are phagocytosed by the APCs. The mechanisms of DNA vaccines are illustrated in Figure 1 . It is interesting to note that immunization may occur rapidly before a DNA vaccine expresses the antigens, and antigens expressed in somatic cells may not qualitatively be the major player in eliciting immune response. Comparing to the secondary role of somatic cells, bone marrow derived antigen presenting cell (APC) activation is an important indicator for successful induction of DNA vaccine [18] . In this study, DNA vaccine was delivered into the skin of mouse ears by gene gun. Immune response was produced after the inoculation site (i.e., the ear) was rapidly removed after immunization before antigens were expressed, indicating that mobile cells are important in elaborating immunity. In another similar study, surgical removal of the injected muscle within 10 min of DNA vaccines administration did not affect the magnitude or longevity of antibody responses to the encoded antigen [19] . Again, the results confirmed the importance of APCs over somatic cells such as myocytes and keratinocytes for eliciting immune responses.