DNA vaccines hold great promise for HIV prevention research

MADRID, SPAIN – OCTOBER 24, 2018

Scientific presentations by the HIV Vaccine Trials Network (HVTN) at the HIV Research for Prevention (HIVR4P) conference showed promising early-stage clinical findings that advance the development of DNA vaccines to prevent HIV infection.

While traditional viral vector vaccines involve weakened or killed forms of whole pathogens or specific protein components that generate antibody and T-cell responses, DNA vaccines aim to deliver a small circular piece of DNA containing genes encoding pathogen antigens directly to cells. The body’s cells use this DNA to produce the antigens that trigger immune responses. Thus far, no DNA vaccines have been approved for human use in the United States. Two presentations at HIV R4P indicated that candidate HIV DNA vaccines can elicit strong anti-HIV immune responses in clinical trial participants.

DNA and protein HIV vaccine regimen elicited stronger antibody and cellular immune responses than a canarypox and protein HIV vaccine regimen.
DNA vaccines are relatively easy and inexpensive to manufacture but do not always produce strong immune responses. HVTN scientists reported that an experimental HIV DNA and protein vaccine regimen assessed in the HVTN 111 clinical trial elicited stronger immune responses in study participants than a regimen based on canarypox and protein vaccines evaluated in the HVTN 100 clinical trial.

The HVTN 111 regimen included groups who received two initial, or “prime,” doses of a DNA vaccine given either by needle and syringe or by a needle-free injector called a Biojector, followed by two booster doses of the DNA vaccine plus an HIV protein containing an adjuvant to enhance immune responses. HVTN 100 tested a regimen comprising two doses of a canarypox-vectored vaccine called ALVAC, followed by two doses of ALVAC plus the same adjuvanted protein used in HVTN 111. These results suggest that DNA vaccines should be considered for future HIV vaccine strategies. The findings were reported at an HIVR4P oral presentation titled DNA-prime Induces Higher Magnitude Humoral Responses than ALVAC-prime in HIV Vaccine Regimens with the Same Protein Boost.

file
Illustration by Lisa Donohue

"Our results suggest that HIV vaccine strategies should prioritize DNA priming with an adjuvanted protein boost if the quality and durability of antibody and cellular responses also indicate superiority over ALVAC priming,” said Zoe Moodie, Ph.D., faculty statistician at the Vaccine and Infectious Disease Division at Fred Hutchinson Cancer Research Center. “Further evaluation is needed to determine whether the delivery of DNA by Biojector elicits stronger cellular immune responses that warrant its use over the traditional needle and syringe,” she concluded.

Vaccine delivery by electroporation through the skin requires one-fifth of the dose needed for an intramuscular vaccine for an equivalent immune response.
Researchers are pursuing strategies to make DNA vaccines more effective in humans. One new approach is detailed in the abstract Immune Responses to PENNVAX-GP® HIV DNA Vaccine plus IL-12 are Equivalent or Superior when Delivered by Intradermal vs. Intramuscular Electroporation, presented today at an oral scientific session. In this phase 1 HVTN 098 clinical trial, DNA vaccines were delivered via patients’ skin or muscle with an electroporation device, which makes cell membranes more permeable to DNA with a pulse of electricity.

The electroporation device was used to encourage cells to take up the DNA vaccine, called PENNVAX-GP. The vaccine was delivered along with IL-12 (interleukin 12), which can stimulate the function of T-cells, a key component of the immune response. The study authors found that with the use of electroporation and IL-12, higher magnitude immune responses to the DNA vaccine were seen, and that delivery through the skin required only one-fifth of the dose needed for a vaccine delivered to the muscle1 to achieve the same immune response.

Dr. J. Joseph Kim, Inovio’s President & CEO, said, “Inovio and the HVTN share a goal to develop a successful HIV vaccine as soon as possible.  We are grateful for their partnership in that effort.  At Inovio, we are truly pleased to see these robust immune response data and they are remarkably consistent with our other vaccine data reported from our Ebola, Zika and MERS clinical trials in terms of demonstrating very favorable vaccine response rates with a good safety profile. We look forward to further advancing PENNVAX-GP into later-stage clinical development with our partners and collaborators.”    

Much remains to be accomplished in the field of DNA vaccines, but HVTN researchers are making bold strides in their pursuit to find a safe and effective HIV vaccine.

We are on a scientific journey to find a safe and effective HIV vaccine to prevent new HIV infections in the future
An estimated 35 million lives have been lost since the HIV/AIDS pandemic began more than three decades ago.  The World Health Organization (WHO) estimated that 37.6 million people were living with HIV in 2016, and 1.8 million new infections were documented in the same year. There are an estimated 5,000 new HIV infections daily around the world. Key populations at risk of acquiring HIV, irrespective of epidemic type or local context, include men who have sex with men, people in prisons and other closed settings, sex workers and their clients, transgender people and people who inject drugs.

The HVTN is the world’s largest publicly funded collaboration facilitating the development of vaccines to prevent HIV/AIDS and has together with global partners demonstrated significant scientific progress in pursuit of a safe and effective HIV vaccine.  Through an inclusive strategy, and by forging in-country relationships on four continents at 44 clinical trial sites, the network, headquartered at the Fred Hutchinson Cancer Research Center, works collaboratively with global communities and partners in the search for an effective HIV vaccine. Primarily funded by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH), the network currently manages 18 active clinical trials of which four are large-scale in-human efficacy trials.

###


About Inovio Pharmaceuticals, Inc.
Inovio is a late-stage biotechnology company focused on the discovery, development, and commercialization of DNA immunotherapies that transform the treatment of cancer and infectious diseases. Inovio’s proprietary platform technology applies next-generation antigen sequencing and DNA delivery to activate potent immune responses to targeted diseases. The technology functions exclusively in vivo, and has been demonstrated to consistently activate robust and fully functional T cell and antibody responses against targeted cancers and pathogens. Inovio is the only immunotherapy company that has reported generating T cells whose killing capacity correlates with relevant clinical outcomes. Inovio’s most advanced clinical program, VGX-3100, is in Phase 3 for the treatment of HPV-related cervical pre-cancer. Also in development are Phase 2 immuno-oncology programs targeting head and neck cancer, bladder cancer, and glioblastoma, as well as platform development programs in hepatitis B, Zika, Ebola, MERS, and HIV. Partners and collaborators include MedImmune, Regeneron, Roche/Genentech, ApolloBio Corporation, The Wistar Institute, University of Pennsylvania, Parker Institute for Cancer Immunotherapy, CEPI, DARPA, GeneOne Life Science, Plumbline Life Sciences, Drexel University, NIH, HIV Vaccine Trials Network, Fred Hutchinson Cancer Research Center, National Cancer Institute, U.S. Military HIV Research Program, and Laval University. For more information, visit www.inovio.com.
 

About Fred Hutchinson Cancer Research Center
At Fred Hutchinson Cancer Research Center, home to three Nobel laureates, interdisciplinary teams of world-renowned scientists seek new and innovative ways to prevent, diagnose and treat cancer, HIV/AIDS and other life-threatening diseases. Fred Hutch’s pioneering work in bone marrow transplantation led to the development of immunotherapy, which harnesses the power of the immune system to treat cancer. An independent, nonprofit research institute based in Seattle, Fred Hutch houses the nation’s first National Cancer Institute-funded cancer prevention research program, as well as the clinical coordinating center of the Women’s Health Initiative and the international headquarters of the HIV Vaccine Trials Network.

 


1The potent immunogenicity and dose-sparing effect of intradermal delivery of DNA delivered via electroporation (boosted with MVA) was published in 2008. The Journal of Infectious Diseases, Volume 198, Issue 10, 15 November 2008, Pages 1482–1490, https://doi.org/10.1086/592507

 

MEDIA CONTACT:
Aziel Gangerdine
HVTN: Director of Communications
C 206.384.0945 / O 206.667.7875
agangerd@fredhutch.org
www.hvtn.org
Facebook.com/helpendhiv
Twitter.com/helpendhiv