Vaccines
Members of the TNF Superfamily (TNFSF) of ligands are among the most powerful immunostimulatory molecules known, allowing them to be used as immunological "adjuvants" for vaccination. At this early stage of product development, the company has found applications for the following TNFSF ligands:
UltraCD40L (SP-D-CD40L) - strong stimulation of CD8+ killer T cell responses - useful for antiviral vaccines
UlraGITRL (SP-D-GITRL)- strong stimulation of CD4+ helper T cell responses, moderate stimulation of CD8+ killer T cell responses, and moderate stimulation of antibody responses - useful for many kinds of vaccines
UltraBAFF (SP-D-BAFF) - strong stimulation of antibody responses - useful for vaccines that rely on antibodies for protection
Example: HIV Vaccine
Mice were vaccinated by intramuscular injections of plasmid DNA encoding a secreted form of the HIV-1 Gag protein (pScGag) or an empty plasmid as a control. Some mice received a second plasmid encoding either the natural membrane form of CD40L (pMemCD40L) or the company's multimeric secreted form of CD40L (UltraCD40L or pSP-D-CD40L). Then, spleen cells were analyzed using an ELISPOT assay for interferon-gamma production which visualizes each individual CD8+ killer T cell as a brown dot. As shown, UltraCD40L (pSP-D-CD40L) is a superior adjuvant for this type of antiviral vaccine. It is now being tested for this purpose in macaque monkeys.
Further details on the use of UltraCD40L (SP-D-CD40L) in an HIV vaccine were published in the Journal of Virology 80:1762-72, 2006.
Other Vaccine Targets
Chronic Hepatitis B Virus (HBV) infection: UltraCD40L will tested in combination with HBV antigens to determine if it can treat chronic HBV infection, a major cause of cirrhosis and liver cancer worldwide.
Malaria: The addition of UltraGITRL to a DNA vaccine led to nearly complete protection of mice challenged with Plasmodium yoelii-infected red blood cells.
Influenza: DNA vaccines can be rapidly modified and mass-produced, making them ideal for evolving threats like avian influenza. Using an innovative vaccination strategy, the addition of UltraGITRL or UltraBAFF can be used to generate protective antibodies in just 7 days.
Biodefense Vaccines: Developing vaccines against anthrax, Ebola, smallpox, plague, and other microbes has been a priority. The use of UltraCD40L, UltraGITRL, or UltraBAFF as adjuvants could become an essential component of such vaccines.
