Despite the well-known successes of traditional vaccines, they are not very effective at inducing protection against intracellular pathogens or cancers because they do not effectively activate cellular immune responses. Recently, DNA-based vaccines have been found as a way to activate cellular immune responses. However, while many DNA vaccines are capable of inducing potent and long-lasting cytotoxic T lymphocyte activity and antibody responses against a variety of pathogens and cancers, the immune response they elicit to certain antigens is suboptimal and unable to provide long-lasting protection. These observations have spurred the search for adjuvants for DNA vaccines. The purpose of this study is to determine if administration of PCE, a natural product obtained from the extracts of pinecones, can function as a DNA vaccine adjuvant. Based upon preliminary evidence suggesting that PCE may modulate an immune response by (a) inducing the differentiation and activation of antigen presenting cells (APC); (b) enhancing the local production of cytokines/chemokines associated with the recruitment, activation, maturation and fucntion of APC; and/or (c) enhancing the expression of APC surface molecules required for antigen presentation, we hypothesize that PCE will significantly enhance the response to DNA vaccines. We will systemically address this hypothesis within 3 specific aims.
In Aim 1 the optimal dose and route of delivery (oral or intramuscular injection) of PCE that reproducibly enhances CTL and antibody responses to 4 model DNA vaccines (GFP, lacZ, Hepatitis surface antigen, or HIV-gag) will be determined.
In Aim 2 the vaccine producing the greatest response in Aim 1 will be used to establish whether PCE induces memory responses to the vaccine antigen. This will be determined by challenging mice post-vaccination with tumor cells expressing the same antigen. The suppression of tumor initiation or growth will signify a memory response.
In Aim 3 the affects of PCE administration on the immune response to a protein-based vaccine will be examined. Mice treated with or without PCE will be injected with the antigen determined to produce the greatest response in Aim 1. The levels of antigen-specific antibodies and CTL will be examined. Overall, this study will determine if PCE can be safely and effectively used as a DNA vaccine adjuvant
