Interim study data of a modified HIV vaccine regimen presented at AIDS 2016 demonstrated increased efficacy over previous attempts and supports expansion into larger clinical trials.
This announcement comes alongside trial enrollment updates for another HIV vaccine developed by Janssen Pharmaceuticals, and increasing focus on antibody-mediated prevention (AMP) strategies.
HVTN 100 surpasses expectations
Previous data from the RV144 HIV vaccine trial demonstrated a 31% rate of vaccine efficacy among Thai participants at 3.5 years. To improve responses and further evaluate safety, Linda-Gail Bekker, MBChB, PhD, FCP(SA), president-elect of the International AIDS Society (IAS) and deputy director of the Desmond Tutu HIV Center in Cape Town, South Africa, and colleagues conducted the HVTN 100 phase 1/2 trial, which modified components of the RV144 vaccine and tailored it for use with a specific subtype of the disease.
“HVTN 100 used the same vaccines that RV144 tested, but made them specific to the Clade C subtype of HIV, which is widespread in southern Africa,” Bekker said in a press release. “We also changed the adjuvant used with one of the vaccines, with the goal of eliciting a more powerful immune response, and added a booster injection to prolong the period of protection.”
In the trial, Bekker and colleagues randomly assigned 252 uninfected South African participants to receive vaccine or placebo. Although 12-month booster vaccinations are still underway, the researchers presented interim data comparing humoral and cellular responses measured at 2 weeks after the 6-month vaccination to those reported in the initial RV144 trial.
Bekker and colleagues observed no safety issues among the 185 vaccine and 37 placebo recipients included in the interim analysis, and all recipients developed immunoglobulin G (IgG) binding antibodies to the three envelope insert antigens with significantly higher titers than the corresponding RV144 antigens. CD4 T-cell response were greater in HVTN100 than in RV144 (57.5% vs. 41.4%; P = .002), and 80% of participants demonstrated an IgG response to at least one of the three vaccine-matched V1V2 antigens.
These outcomes exceeded pre-determined efficacy criteria, Bekker said, and provide the go-ahead for HVTN 702. This larger placebo-controlled study will enroll 5,400 uninfected participants at 15 South African sites before the end of the year, according to the press release, and involve five injections over the course of 1 year as well as 2 years of follow-up to determine whether the modified RV144 regimen elicits sustained protection.
“It is gratifying to see vaccines that were designed and manufactured specifically for South Africa meet and even exceed the criteria established to advance them into the large efficacy trial,” Larry Corey, MD, principal investigator for the HIV Vaccine Trials Network and professor of medicine and laboratory medicine at the University of Washington, said in the release. “HVTN 702 is a pivotal study that could lead to a licensed HIV vaccine in South Africa — the first preventive HIV vaccine worldwide.”
Trials continuing for other vaccines, AMP strategies
Further vaccine news from the conference included an announcement from Janssen Pharmaceutical confirming the enrollment of 400 South African, Rwandan, Ugandan, Thai and American participants in a phase 1/2a study of its investigational heterologous prime-boost HIV-1 vaccine regimen. According to a press release, the company and its partners will compare results from this trial, which uses a trivalent adenovirus serotype 26 (Ad26) vectored vaccine, to another recently announced phase 1/2a trial of a regimen built on a tetravalent Ad26 vaccine.
“No viral epidemic in history has been eliminated without an effective vaccine,” Hanneke Schuitemaker, MD, head of viral vaccines for Janssen Pharmaceuticals, told Infectious Disease News. “The introduction of a preventive HIV vaccine will therefore be critical and could dramatically reduce new HIV infections and AIDS-related deaths. Johnson & Johnson is collaborating with multiple partners on a global HIV vaccine approach which, based on very encouraging preclinical results, may ultimately prove to be a strategy for protecting against HIV infection.”
Also presented at AIDS 2016 was an update on the first large-scale human trials of AMP strategies: HVTN 704/HPTN 085 and HVTN 703/HPTN 081. These studies are both undergoing enrollment, according to the IAS release, and will determine the safety and tolerability of broadly neutralizing antibody (bNAb) VRC01 infusion among men who have sex with men, transgender individuals and heterosexual women on four continents.
“If efforts in developing an HIV vaccine based on the induction of bNAbs are successful, this achievement will represent the most elegant and complex scientific approach toward any vaccine in history,” Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, wrote in a recent JAMA editorial. “In contrast, if unsuccessful, this experience will be recorded as the most highly sophisticated and scientifically elegant proof that the development of such a vaccine is impossible. Hopefully, the former and not the latter will be true.” – by Dave Muoio
Bekker LG, et al. Abstract TUAX0102LB. International AIDS Conference. July 18-22, 2016. Durban, South Africa.
Fauci AS. JAMA. 2016;doi:10.1001/jama.2016.7538.
Disclosures: Fauci reports no relevant financial disclosures. Schuitemaker is an employee of Janssen Pharmaceuticals. Infectious Disease News was unable to determine Bekker and Corey’s financial disclosures at the time of publication.