Glycoprotein D Vaccine Adjuvant
Investigators at The Wistar Institute have developed a novel method for improving the immune response to vaccination by combining specific target antigens with a non-specific adjuvant. Wistar scientists have developed a new highly effective carrier protein adjuvant by fusing a Herpes simplex virus glycoprotein D (gD) sequence to the vaccine immunogen sequence. Glycoprotein D is a viral envelope protein that is normally expressed on the surface of cells infected with Herpes virus. The recombinant gD-antigen protein sequence preserves the structures responsible for interaction with an immune cell receptor, which is involved in controlling immune responses. The efficacy of recombinant gD as an adjuvant has been demonstrated with antigens from human papillomavirus (HPV), human immunodeficiency virus (HIV) and Influenza A virus.
In a mouse model of HPV-induced tumors, vaccination with a viral vector vaccine carrying HPV oncoproteins fused into the gD sequence induced strong immune response to the oncoproteins and resulted in significant tumor regression in mice with large tumor masses. Therefore, the gD adjuvant may be particularly useful for the development of a therapeutic HPV vaccine.
Unlike many carrier protein adjuvants that are targeted to intracellular compartments, the glycoprotein D-antigen proteins are expressed on the cell surface. This significantly reduces the likelihood of deleterious interaction with intracellular proteins such as those implicated in malignant transformation. The gD adjuvant may be applicable to multiple vaccine delivery methods. Vaccines in the form of naked DNA and viral vectors (adenovirus vectors and adeno-associated virus vectors) have been tested; testing of other vaccine delivery platforms are underway.
The HSV glycoprotein D is an effective adjuvant for DNA, viral vector, and protein vaccines. The glycoprotein D adjuvant has application in the development of new effective therapeutic and preventative vaccines for viral infections and cancer.
U.S. Patent Application No. 12/438,889 (US-2009-0246220, published 10/01/2009).
Wistar is seeking corporate partners to further develop this technology. Exclusive or non-exclusive licenses will also be considered.
Lasaro et al., 2008. “Targeting of antigen to the herpesvirus entry mediator augments primary adaptive immune responses”. Nature Medicine 14:205-212.
Lasaro et al., 2005. “Anti-tumor DNA vaccines based on the expression of human papillomavirus-16 E6/E7 oncoproteins genetically fused with the glycoprotein D from herpes simplex virus-1”. Microbes and Infection 7:1541-1550.