PLYMOUTH MEETING, Pa.—In mid-May, Inovio Pharmaceuticals, Inc. announced that its HIV vaccine, Pennvax-GP, maintained durable and robust immune responses at month 12, a full six months after the last dose in a Phase 1 clinical study. Inovio previously reported that Pennvax-GP elicited the highest overall levels of immune response rates (cellular and humoral) ever demonstrated in a human study by an HIV vaccine. To potentially prevent and treat HIV, Pennvax-GP consists of a combination of four HIV antigens designed to generate both antibody and T-cell responses and cover multiple global HIV strains.
The most prevalent HIV-1 clades are B (found mainly in North America and Europe), A and D (found mainly in Africa) and C (found mainly in Africa and Asia). HIV-1 clade C accounts for 48 percent of worldwide and 51 percent of African-HIV type 1 cases. It is the most rapidly spreading subtype of HIV. Although highly active antiretroviral therapy regimens have dramatically transformed the treatment of the disease in developed countries, safe and effective HIV vaccines are needed to stop the spread of disease.
As Dr. Scott White, vice president of clinical development at Inovio, tells DDNews, “The Pennvax-GP vaccine is a DNA vaccine that includes multiple HIV antigens (gag, pol and env) which is being developed in partnership with the HVTN for use as a prophylactic vaccine. Pennvax-GP differs from other HIV prophylactic vaccines in that the technology is based on synthetic consensus DNA as the source of vaccine antigen. Thus far it has delivered the highest percentage of antibody and T cell response rates of any vaccine platform.”
The breakthrough data was presented at a plenary session at the 2018 HIV Vaccine Trials Network (HVTN) Full Group Meeting by the protocol co-chair of the HVTN 098 study, Dr. Stephen De Rosa, a research associate professor of laboratory medicine at the University of Washington and Fred Hutchinson Cancer Research Center. The HVTN 098 trial is the first clinical study of Pennvax-GP. The randomized, placebo-controlled multi-center study enrolled 94 subjects (85 vaccine and nine placebo) to characterize and optimize a four-dose regimen of Pennvax-GP DNA vaccine administered by intradermal (ID) or intramuscular (IM) administration in combination with a DNA encoded immune activator, IL-12 (INO-9012).
More comprehensive immune analyses demonstrated that Pennvax-GP (plus IL-12) generated HIV-specific CD4+ T cell and binding antibody response rates close to 100 percent when delivered with CELLECTRA intramuscular or intradermal devices. For instance, 96 percent (26 of 27) of participants receiving Pennvax-GP and IL-12 via the IM route demonstrated a CD4+ T cell response, while the same percentage (96 percent, or 27 of 28) of participants receiving the vaccine formulation via ID administration also displayed anti-HIV CD4+ T cell responses—even though those vaccinated via intradermal administration received one-fifth the total dose, compared to those vaccinated via the intramuscular device.
“What we view as exciting about the Pennvax-GP program is how it demonstrates the power of Inovio’s specific Aspire immunotherapy technology. When it comes to nucleic acid-based vaccines, they are not all equal. Inovio’s combination of DNA sequence optimization and CELLECTRA delivery technology is demonstrating consistently superior immunogenicity, compared to other vaccine platforms with an excellent safety and tolerability profile,” notes White. “The CELLECTRA delivery technology is an integral part of the platform’s ability to drive both antibody and cellular immune responses, so plans are to continue using this delivery technology during Pennvax-GP clinical development. ”
The new data from subjects followed for a full year of the study showed that the immune responses were maintained in most subjects at month 12, as evidenced by the durability of activated T cells as well as the magnitude of responder rates. Notably, the percentage of patients who had CD8+ T cell responses immediately after the last dose stayed the same or even increased slightly over the six-month followup period, clearly demonstrating durable vaccine-generated memory responses.
“Nearly all the immunogenicity assays for HVTN 098 have been completed, and the results collectively and consistently show nearly all participants had detectable CD4+ T cell and antibody responses to envelope and over 50 percent had CD8+ T cell responses,” De Rosa stated. “Not only were these high response rates exceptional, we further observed that high T cell response rates, especially for those of very difficult to generate CD8+ T cells, were maintained at month 12 time point or a full six months after the last dose. Further studies will be needed to determine if this vaccine candidate can safely and effectively prevent HIV infection.”
These results are from a study supported by the HVTN and the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, in collaboration with Inovio. Development of Inovio’s Pennvax-GP vaccine has been funded through a five-year, $25-million NIAID contract previously awarded in 2009 to Inovio and its collaborators. In addition, Inovio and its collaborators were awarded an additional five-year $16-million Integrated Preclinical/Clinical AIDS Vaccine Development grant in 2015 from NIAID.
Dr. J. Joseph Kim, Inovio’s president and CEO, said, “We are truly pleased to see these robust and durable immune response data, which are among the highest ever responses we’ve seen with an HIV vaccine, and they are remarkably consistent with our recent data reported from our Ebola, Zika and MERS clinical trials in terms of demonstrating nearly 100 percent vaccine response rates with a very favorable safety profile. Furthermore, our newer and more tolerable intradermal vaccine delivery device showed that we can elicit very high immune responses at a much lower dose. We look forward to further advancing Pennvax-GP into later-stage clinical development with our partners and collaborators.”