Inovio Pharmaceuticals, Inc., a leader in the development of therapeutic and preventive vaccines against cancers and infectious diseases, announced today that an article describing 100% protection of non-human primates against a highly pathogenic monkeypox challenge after vaccination with its smallpox DNA vaccine has been published in The Journal of Infectious Diseases. Inovio’s DNA vaccine demonstrated strong antibody-based immune responses similar to that of the currently approved live viral vaccine (Dryvax(R)). The study conducted by Inovio scientists and their collaborators is described in this published paper, entitled, “Multivalent Smallpox DNA Vaccine Delivered by Intradermal Electroporation Drives Protective Immunity in Nonhuman Primates Against Lethal Monkeypox Challenge.”
The study demonstrated that a synthetic, multivalent, low-injection volume, highly concentrated DNA vaccine delivered by a minimally invasive, novel skin electroporation microarray can generate potent and multi-functional immunity in monkeys and offer protection from a highly pathogenic monkeypox challenge. The diverse, high-titer antibody response produced against eight different DNA-encoded antigens delivered simultaneously as a single formulation has not been previously described in the scientific literature.
The monkeys were immunized three times at one-month intervals and were challenged with a lethal dose of monkeypox virus one month later. All ten animals vaccinated with the DNA vaccine survived the lethal monkeypox challenge, showed significant reduction in the amount of virus circulating in the body, and experienced decreased disease-related sickness in a dose dependent manner (measured by clinical signs of disease and changes in body weight and temperature) as compared to control animals that did not receive the DNA vaccine. Only one macaque from the control group (4) survived the challenge but with lesions still present at the end of the observation period (day 27 post-challenge).
Stanley A. Plotkin, M.D., Emeritus Professor, Wistar Institute and University of Pennsylvania, stated: “These results are remarkable in many ways. DNA for multiple smallpox genes that code for protective antigens was given transcutaneously by electroporation and the responses were protective against monkeypox, a closely related virus. The responses included antibodies, necessary for protection against smallpox, but notable because prior DNA vaccines have had difficulty eliciting antibodies. Finally, this DNA vaccine is actually safer than the old smallpox vaccine and could be useful in the event of a bioterrorist attack necessitating rapid vaccination of people, some of whom might be immunosuppressed; and also if monkeypox is again introduced into the United States.”
The threat of a smallpox-based bioterrorist event has heightened the importance of developing a new, safer vaccine approach for these pathogens to complement or replace older poxviral vaccine platforms. The approved live viral vaccine for smallpox has several side effects and is contraindicated in many individuals, which reduces the general acceptance and feasibility of using the currently stockpiled smallpox vaccine to protect the general populace from bioterrorism.
Inovio scientists used gene sequences taken from the smallpox virus to create a multi-antigen DNA vaccine that was delivered using Inovio’s proprietary electroporation technology – which uses short, localized and controlled electric pulses to enhance the uptake and effectiveness of DNA vaccines.
A formulation combining eight different DNA plasmids was made possible by technological innovations from VGXI, Inc., a DNA contract manufacturing affiliate of Inovio that enables the production of highly concentrated DNA vaccine products (at a product concentration of greater than 10 mg/mL). The funding for this study was provided by the Defense Threat Reduction Agency (DTRA) of the U.S. Department of Defense.
Dr. J. Joseph Kim, president and CEO of Inovio Pharmaceuticals, said, “The development of novel vaccines for biosecurity concerns such as smallpox has been an important area of development for Inovio’s potent DNA vaccines platform. This study indicates the potential to develop a smallpox vaccine with similar efficacy to the important conventional vaccine responsible for eradicating smallpox, but without its notable safety concerns. With further collaborative funding we would look forward to advancing the development of this vaccine candidate to protect humans.”
Date: December 7, 2010
Source: Inovio Pharmaceuticals, Inc.
Filed Under: Drug Discovery
