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.
Vaccine for Prevention of Rabies Infections in Humans
Researchers at Wistar have developed a new rabies vaccine that has the potential to produce the long-lasting immunity to rabies that is required for an effective prophylactic vaccine. This vaccine is derived from recombinant chimpanzee adenovirus (rAdC68) that contains the DNA sequence of the rabies glycoprotein.
In non-human primates, this adenovirus-based vaccine produces long-lasting immunity after just one intramuscular injection, even in the presence of pre-existing immunity to human adenovirus. In ongoing studies, primates immunized with one does of the rAdC68 rabies vaccine showed no decline in serum antibody levels after six months. Wistar is seeking a partner to develop this vaccine for prevention of human rabies infection, either as a single vaccine or in combination with the current human diploid cell rabies vaccine. The adenovirus-based vaccine is less expensive to produce, maintain, and distribute than the current human rabies vaccines. This new immunization approach may make it feasible and cost-effective to administer prophylactic rabies vaccines to children in areas where rabies still commonly infects dogs and other companion animals.
Monoclonal Antibody to Phosphorylated p53
The gene for the tumor suppressor protein p53 encodes a nuclear phosphoprotein that is altered by mutation or deletion in about 50% of human tumors. When single point mutations modify p53 structure and function, post-translational modifications of mutated p53 molecules are expected to interfere even more strongly with its function of controlling cell growth and division. The most prominent post-translational modification of p53 is phosphorylation at one or more of many sites along the protein. Wistar researchers developed a double-phosphorylated peptide that is phosphorylated at the Ser378 and Ser392 sites of human p53. This peptide was then used to generate a highly sensitive monoclonal antibody (mAb p53-18) to p53 protein. This antibody can be used to distinguish the phosphorylated from the non-phosphorylated forms of p53. Since sera from cancer patients preferentially label the double-phosphorylated p53 peptide, the mAb p53-18 may be useful in developing cancer diagnostics.