Drug Discovery & Development - June 28, 2010

Inovio Pharmaceuticals, Inc., a leader in the development of therapeutic and preventive vaccines against cancers and infectious diseases, announced that the peer-reviewed journal Molecular Therapy has published a paper entitled "Comparative Analysis of Immune Responses Induced by Vaccination With SIV Antigens by Recombinant Ad5 Vector or Plasmid DNA in Rhesus Macaques." The paper, co-authored by researchers from Merck, University of Pennsylvania School of Medicine, and Inovio Pharmaceuticals, notes that significant advances in the design, formulation, and delivery of DNA plasmid-based vaccines have dramatically increased their ability to induce antigen-specific immune responses. In this head-to-head comparison with an adenovirus serotype 5 (Ad5) vaccine considered to be the most immunogenic among viral vectors, Inovio's optimized SynCon(TM) DNA vaccine delivered using its proprietary electroporation technology demonstrated numerous advantages in both magnitude and breadth of immune responses produced in non-human primates.

Compared to Ad5, the SynCon DNA vaccine resulted in:

• Significantly stronger antigen-specific cellular immune responses, in particular CD8+ T cells. T cells are considered instrumental in clearing cancerous or infected cells from the body. Such responses are therefore imperative to achieving sufficient potency in new vaccines against cancers and chronic infectious diseases such as HIV and hepatitis C virus. Importantly, Ad5 immunizations failed to boost immune responses following the first immunization, whereas immune responses from DNA vaccination were continually boosted even after four immunizations.

• Increased breadth of T cell-based immune responses. CD4+ and CD8+ T cell immune responses produced with DNA vaccination were broader and produced multiple immune molecules called cytokines (IFN, IL-2, TNF-a, and CD107a). Broad immune responses are considered an important potential marker for vaccine efficacy.

Immune responses that were long-lasting and maintained at high levels.

Dr. David Weiner, Professor, Department of Pathology & Laboratory Medicine and Chair, Gene Therapy and Vaccines Program at the University of Pennsylvania, and the lead author of the paper, commented: "While Ad5 is particularly potent after a single immunization, its apparent susceptibility to pre-existing immune responses is a concerning limitation. We were pleased to see the superior magnitude and quality of immune responses generated by Inovio's SIV DNA vaccine delivered using electroporation. Moreover, the ability of this technology to continuously boost immune responses after multiple immunizations is an accomplishment that bodes well for the application of this vaccine platform for diseases requiring strong T cell responses, such as HIV, hepatitis C virus, and cancers." Dr. Weiner is also chairman of Inovio's scientific advisory board.

Dr. J. Joseph Kim, Inovio's CEO and also a co-author of the paper, said: "This study highlights that Inovio's DNA vaccine platform has achieved levels of immune responses previously not achievable and is playing an important role in further advancing this important new generation of vaccines. These results have more recently been supported by the human data reported from our HPV clinical trial, which demonstrated unprecedented levels of cellular and humoral (antibody) responses."

Inovio's PENNVAX-B HIV vaccine is currently being tested in two separate Phase I clinical studies (preventive and therapeutic settings). Inovio is developing two additional globally targeted HIV vaccine candidates, PENNVAX(TM)-G and PENNVAX(TM)-GP, in a collaboration with the US Military HIV Vaccine Research Program and via a multi-year $23.5 million NIAID HIV vaccine development contract, respectively.

Date: June 22, 2010

Source: Inovio Pharmaceuticals, Inc.

http://www.dddmag.com/news-Inovio-DNA-Vaccine-Shows-Advantages-Over-Viral-Methods-62810.aspx