Inovio Pharmaceuticals, Inc. announced that its Ebola vaccine, INO-4212, was safe, tolerable, and generated strong T cell and antibody responses in its fully enrolled phase I study of 75 healthy subjects. Detailed immunogenicity and safety data is being prepared for peer-reviewed publication. In previously reported preclinical testing in mice and non-human primates, the Ebola vaccine protected 100 per cent of immunised animals from sickness and death following exposure to a lethal dose of Ebola virus.

This human study (CT.gov: NCT02464670) was conducted by an Inovio-led consortium, which was selected and awarded $45 million by the US Defense Advanced Research Projects Agency (DARPA) in 2015 to take a multi-faceted approach to prevent and treat Ebola infection.

This initial trial evaluated INO-4212 in five groups of healthy subjects. INO-4212 consists of two optimized SynCon DNA plasmids coding for the Ebola glycoprotein antigen from circulating Ebola strains from 1975 - 2014. These plasmids were tested separately and together in muscle and skin in five study arms, one including Inovio’s DNA-based IL-12 immune activator. Of 69 evaluated subjects, 64 (92.7 per cent) seroconverted and mounted a strong antibody response to the Ebola glycoprotein antigen following the three dose immunization regimen; 48 subjects (69.6 per cent) seroconverted after only two doses.

Significantly, in the study arm using intradermal (skin) administration, 13 of 13 evaluable subjects (100 per cent) generated antigen-specific antibody responses after only two doses and all remained seropositive after three immunizations. Similarly, in the study arm receiving the vaccine with intramuscular administration in combination with plasmid IL-12, 12 of 13 evaluable subjects (92.3 per cent) demonstrated strong antibody responses after only two immunizations and 13 of 13 (100 per cent) produced strong antibody responses after three immunisations.

The Ebola glycoprotein specific geometric mean antibody titers measured in the five cohorts ranged from over 2,000 to greater than 46,000. Significantly, a majority of vaccinated subjects in each of the five cohorts produced strong Ebola antigen specific T-cell responses as measured by interferon gamma ELISpot analysis.

To date INO-4212 has been well tolerated and has not demonstrated systemic serious adverse effects, such as fever, joint pain, and low white blood cell counts, reported in association with some viral vector based Ebola vaccines currently in development. Moreover, unlike the viral vectored vaccines which must be kept frozen, INO-4212 was formulated in a solution which was kept refrigerated (2-8 C).

The data was presented today by Dr. Niranjan Y. Sardesai, Inovio’s chief operating officer and principal investigator on the DARPA Ebola programme, at The World Vaccine Congress in Washington, DC. Dr. Sardesai said, “The induction of strong Ebola specific antibody and T cell responses has been difficult to achieve in previous human studies. We are pleased by the immune responses achieved using two and three vaccination regimens in humans with our optimized DNA vaccines delivered using electroporation, adding to the successful animal immune response and challenge studies using our approach. We are particularly excited about the positive immunology data using intradermal immunization as this delivery would facilitate even greater clinical and commercial potential for DNA vaccination.”

“These initial data from our Ebola DNA vaccine represent just a first step in this DARPA-funded programme We look forward to rapidly moving this DNA vaccine into larger human studies on the path to product licensure. We are also advancing our Ebola dMAb™ product and expect to clinically test that independently of the DNA vaccine approach,” said Dr. J. Joseph Kim, president and CEO.

Under the DARPA-funded programme Inovio and its collaborators are developing multiple approaches against Ebola. This programme allows for the development and early clinical testing of Inovio's DNA-based vaccine against Ebola; Inovio's therapeutic Ebola dMAb product. This new technology has properties best suited to respond to an Ebola outbreak in that the product could be manufactured expediently on a large scale using proven fermentation technology, is thermal-stable, and may provide more rapid therapeutic benefit (as shown in Inovio’s Chikungunya and dengue programs); and a highly potent conventional protein-based therapeutic monoclonal antibody (mAb) product against Ebola virus infection, co-developed with MedImmune, the global biologics research & development arm of AstraZeneca.