Adjuvant for DNA, RNA, and Viral Vectored Vaccines

Since LMP1 is an cell membrane protein, it must be delivered to cells as a nucleic acid. This can either be done using DNA or RNA vaccines or viral vectored vaccines such as adenovirus (Ad).

Adenoviral (Ad) vectors are being developed as vaccines for malaria, ebola, and other infections. To test the effectiveness of LMP1 as an adjuvant for an Ad vaccine, Ad5 expressing HIV-1 Gag was mixed with Ad5 expressing LMP1 and used to vaccinate mice. Then the spleen cells were harvested and analyzed for antigen-specific CD8+ T cell responses. In parallel, other vaccinated mice were challenged with Vaccinia virus expressing Gag (Vac-Gag).

As shown, Ad5LMP1 dramatically enhanced the vaccine response. Compared to standard Ad5Gag vaccination, the Ad5LMP1-adjuvanted produced almost 3X more antigen-specific CD8+ T cells. This response provided meaningful protection from Vac-Gag and reduced viral load in tissue by almost 3 Logs (1,000-fold less). This implies that AdLMP1 will be useful for improving the effectiveness of many of the Ad-based vaccines now being developed, such as vaccines for Ebola. (Data courtesy of Dr. Geoffrey Stone, Ph.D., University of Miami.)

In other studies, DNA vaccination by intramuscular plasmid injection protected mice from melanoma metastases. Further studies on cancer are being conducted.