Study demonstrates antibody responses within 6 weeks of initial vaccination

SEATTLE, OCTOBER 01, 2019 – An early phase study was conducted in the U.S. in which different combinations of DNA (DNA-HIV-PT123) and protein (AIDSVAX® B/E) vaccines were administered in four randomized treatment groups (T1, T2, T3, T4), to determine which strategy would induce favorable HIV-specific antibody and T-cell responses. The study led by protocol co-chair and Investigator at the Emory Center for AIDS Research Nadine Rouphael, M.D. and chair and professor in the Department of Medicine at the University of Rochester Medical Center Michael Keefer, M.D. demonstrated that DNA (DNA-HIV-PT123) and protein (AIDSVAX® B/E) combination vaccine regimens induced high magnitude and long-lasting binding antibody responses and that more rapid potentially protective immune responses were observed when the vaccine regimens were co-administered. The “DNA priming and gp120 boosting induces HIV-specific antibodies in randomized clinical trial” findings were published in the Journal of Clinical Investigation on September 30.

HVTN 105 was conducted by the HIV Vaccine Trials Network (HVTN), headquartered at the Fred Hutchinson Cancer Research Center and funded by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health, and sponsored by NIAID.

One-hundred and four study participants at low risk for HIV acquisition were enrolled in the study HVTN 105. HVTN 105 was designed to build upon the promising results from the U.S. Army-led RV144/Thai trial, which was the first vaccine clinical trial to ever demonstrate any efficacy in preventing HIV. Study participants were randomized to one of four treatment groups and received intramuscular injections at 0, 1, 3 and 6 months. All vaccine regimens were safe and well tolerated in all treatment groups. Of interest were the comparisons drawn between the vaccine-induced immune responses observed in the T3 and T4 treatment groups. Study participants in the T3 treatment group were vaccinated with a modified RV144 vaccine regimen where the ALVAC vector used in RV144 was substituted with DNA at months 0 and 1 and followed by DNA and protein co-administered at months 3 and 6. Study participants in treatment group T4 were vaccinated with DNA and protein co-administered at all four vaccination timepoints (0, 1, 3 and 6 months)

Because the partial efficacy of the RV144 vaccine regimen seemed to be due to several identified correlates of protection, the authors of the current study investigated whether those same responses were induced by HVTN 105 vaccine regimens. Similar to RV144, the T3 and T4 regimens induced antibodies that bound to gp120 (HIV Env) and the V1V2 region of Env in 95-100% of study participants. T-cell responses were detectable in all treatment groups in HVTN 105. Both T3 and T4 demonstrated high antibody-dependent cellular cytotoxicity (ADCC) and neutralizing antibody responses. The T4 regimen induced a lower IgA/IgG ratio than T3, suggesting an improvement over the RV144 regimen, as this indicates a decrease in this correlate of risk. An additional surprising finding in T4 was the high levels of IgG4 responses, the significance of which in the context of HIV infection is not known.

“Our study shows that there are tools available to us now to improve on the immunogenicity seen in RV144, which may lead to better efficacy in future field trials,” said protocol Co-Chair and Investigator at the Emory Center for AIDS Research Nadine Rouphael, M.D.

Vaccine-induced antibody and T-cell responses, observed in an early-phase clinical trial such as HVTN 105, are important measures to help determine if a vaccine regimen has the potential to be tested as a candidate vaccine in a large-scale trial, powered to determine efficacy.

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Access to manuscript:

Link: https://doi.org/10.1172/JCI128699

Competing interests and source funding: The authors declare that they have no competing interests.

This work was supported by the National Institute of Allergy and Infectious Diseases (NIAID, https://www.niaid.nih.gov/) U.S. Public Health Service Grants UM1 AI068614 [LOC: HIV Vaccine Trials Network], UM1 AI068635 [SDMC: HIV Vaccine Trials Network], UM1 AI068618 [LC: HIV Vaccine Trials Network], UM1 AI069511 [University of Rochester HIV/AIDS Clinical Trials Unit], UM1 AI069470 [Columbia Partnership for Prevention and Control of HIV/AIDS Clinical Trials Unit: College of Physicians & Surgeons and New York Blood Center Clinical Research Sites], UM1 AI069534 and P30 AI450008 [Philadelphia HIV Therapeutics and Prevention Clinical Trials Unit], UM1 AI069439 [Vanderbilt], UM1 AI069481 [Seattle-Lausanne-Kampala Clinical Trials Unit], and UM1 AI069496 [San Francisco Bay Clinical Trials Unit]. Additional support was provided by the National Center for Advancing Translational Sciences, National Institutes of Health (NIH), through Grant Number UL1TR001873 [Columbia]. The DNA vaccine was provided by the IPPOX Foundation, Switzerland through support from the Collaboration of AIDS Vaccine Discovery of the Bill & Melinda Gates Foundation Grant OPP52845. The opinions expressed in this article are those of the authors and do not necessarily represent the official views of the NIAID or the National Institutes of Health (NIH).

Nadine G Rouphael, Cecilia Morgan, Shuying S. Li, Ryan Jensen, Brittany Sanchez, Shelly Karuna, Edith Swann, Magdalena E. Sobieszczyk, Ian Frank, Gregory J. Wilson, Hong-Van Tieu, Janine Maenza, Aliza Norwood, James Kobie, Faruk Sinangil, Giuseppe Pantaleo, Song Ding, M. Juliana McElrath, Stephen C. De Rosa, David C. Montefiori, Guido Ferrari, Georgia D. Tomaras, and Michael C. Keefer on behalf of the HVTN 105 Protocol Team and the NIAID HIV Vaccine Trials Network.

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 NIAID-funded HIV Vaccine Trials Network.

Aziel Gangerdine

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