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Janssen’s HIV vaccine shows promise in clinical trial
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Janssen Pharmaceuticals’ lead investigational HIV vaccine regimen that targets a wide variety of HIV-1 subtypes was well-tolerated and elicited HIV-1 antibody responses in 100% of healthy volunteers, according to first-in-human clinical data from the APPROACH trial.
The vaccine regimen was one of seven different prime-boost vaccine regimens examined in the phase 1/2a trial. The experimental regimens are based on “mosaic” vaccines developed by Janssen, which contain immunogens that are created with genes from different subtypes of HIV-1, according to a press release. The immunogens are delivered through viral vectors, including an engineered version of a common cold virus known as adenovirus serotype 26 (Ad26), according to the NIH, which partly funded the trial.
“One of the barriers we face in vaccine development is the incredible diversity of HIV around the world,” Maria Pau, PhD, senior director and early compound development team leader in the department of infectious diseases and vaccines at Janssen, told Infectious Disease News. “There are many variants of HIV. Our goal is to develop a global vaccine, which would induce immunity against these multiple variants and protect against different subtypes of HIV-1. That, of course, is a challenge”
The trial included 393 adults from the United States, Rwanda, Uganda, South Africa and Thailand. Pau and colleagues randomly assigned approximately 50 participants each to a regimen containing two prime doses of Ad26.Mos.HIV and two boosts with either Ad26.Mos.HIV or MVA-Mosaic and/or two different doses of aluminum phosphate-adjuvanted Clade C gp 140. The vaccinations were administered over 48 weeks.
According to findings presented at the International AIDS Society conference in Paris, all of the vaccine regimens were well-tolerated. The most common adverse events included local pain and headache, which were similar or decreased with subsequent doses.
After the third vaccination, researchers found that most active vaccine regimens elicited antibody responses in 100% of participants. The regimen that elicited the greatest immune responses in humans was the same regimen that also showed the greatest protection against an HIV-like virus in nonhuman primates during preclinical studies, according to the researchers. In the preclinical studies, the regimen reduced the per-exposure risk of infection by 94% and resulted in 66% complete protection following six exposures, the release said. After the fourth vaccination in the APPROACH trial, anti-HIV immune responses further increased. A 12-month follow-up study is currently underway.
“This first-in-human study is important because for the first time, we could evaluate the ability of different vaccine regimens to induce the immune responses that, in our preclinical study, have been shown to improve protection against acquisition of HIV,” Pau said. “What we are very encouraged by in the APPROACH study is that we are seeing the same type of immune responses that we saw in the preclinical evaluation.”
Based on data from the clinical and preclinical trials, researchers selected the regimen incorporating Ad26.Mos.HIV and two boosts with Ad26.Mos.HIV and clade C gp 140 for further evaluation in a phase 2b proof-of-concept trial. However, the NIH said that the decision to launch the trial, which would enroll about 2,600 HIV-negative women in southern Africa, also depends on results slated for late 2017 from another early-stage trial — TRAVERSE — comparing Ad26-based regimens containing either three (trivalent) or four (tetravalent) mosaic antigens. Should the proof-of-concept trial move forward, the NIH anticipates that enrollment would begin in late 2017 or early 2018.
In addition to Janssen and the NIH, the APPROACH trial was also supported by Beth Israel Deaconess Medical Center, the United States Military HIV Research Program at the Walter Reed Army Institute of Research, the Henry M. Jackson Foundation for the Advancement of Military Medicine, the National Institute of Allergy and Infectious Diseases, the Ragon Institute, the International AIDS Vaccine Initiative and the HIV Vaccine Trials Network.
“It is an exciting time,” Pau said. “Yes, there have been triumphs and setbacks in the past. But there is new optimism based on this science and new insights from our clinical and preclinical data. We believe there will be a vaccine within our lifetime.” – by Stephanie Viguers
Reference:
Tomaka F, et al. Selection of a lead HIV-1 vaccine regimen in APPROACH, a Phase 1/2a study evaluating seven heterologous prime boost regimens using mosaic Ad26 and -MVA vectors combined with soluble Env protein. Presented at: IAS Conference on HIV Science; July 23-26, 2017; Paris.
Disclosure: Pau is an employee of Janssen Pharmaceuticals.