APPROACH Study

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Mosaic Design
APPROACH, a preventive vaccine study, seeks to address more than one clade
by Jeannie Wraight

Over the past thirty-plus years, strategies such as Treatment as Prevention, PrEP, syringe exchange, and condom education have succeeded in reducing new HIV transmission rates across the globe. However, a preventive vaccine remains a priority among many researchers, advocates, policymakers and other stakeholders, as a method that is not reliant on human behavior but essential to definitively ending the spread of HIV.

Due to the versatile and diverse nature of HIV, a vaccine that would be effective on a global scale in eliciting strong immune responses across all clades (strains) of HIV presents difficulties that researchers are struggling to overcome. However, results of a multi-centered, HIV vaccine clinical trial appear promising.

The recently released long-term results of APPROACH, a Phase I/IIa preventive vaccine study, show a favorable safety profile and a robust immune response to a mosaic-based HIV preventive vaccine made by Janssen Pharmaceuticals. Investigators found the viral vectored mosaic vaccine Ad26.Mos.HIV to have no serious vaccine-induced adverse events, with the vaccine eliciting robust humoral and cellular HIV-1 immune responses in study participants.

Healthy participants (aged eighteen to fifty) were enrolled in the APPROACH study at twelve clinics in South Africa, Rwanda, Uganda, the U.S. and Thailand. 393 HIV-negative participants received various vaccine and booster combinations, or placebo, in a total of eight separate study arms.

The prime vaccine is a viral vector vaccine based on adenovirus serotype 26 (Ad26). This vaccine is unique as it includes three HIV genes with a mosaic design, including sequences from numerous HIV subtypes. This design could allow for a response across most clades of HIV, making it potentially effective as a global vaccine.

Across the seven arms (the eighth was placebo) participants received four injections. The first two injections were prime doses of Ad26.Mos.HIV (at weeks 0 and 12). The 2 booster vaccinations, at weeks 24 and 48, included Ad26.Mos.HIV, or a separate mosaic component, and/or a clade C HIV gp140 envelope protein adjuvanted by aluminum phosphate.

After the last vaccination, researchers found that most of the study participants developed vaccine-induced antibody and cellular immune responses. This means that the immune system recognized the harmless fragments of HIV that were a part of the vaccine as a threat, and responded by releasing antibodies and by generating cellular immune responses. Indeed, antibodies alone may not be enough to prevent HIV infection—a cellular response may be necessary to destroy infected cells to prevent the spread of HIV from one cell to another and the virus from taking hold in the body.

Importantly, most of these cellular responses as well as the antibody responses were still present one year after the last vaccination. Degrees of response varied across the seven arms but were largely consistent.

In addition to the 393 human participants, a parallel study was performed in rhesus monkeys where the monkeys received one of five different vaccine regimens. The regimen that was most effective in humans also showed the highest rate of immune response in monkeys and a sixty-seven percent protection rate against a simian humanized version of HIV (SHIV).

Based on the initial safety and immunogenicity results of APPROACH and the protection in monkeys, a second study called Imbokodo has been initiated in a total of twenty-six sites in five Southern African countries: South Africa, Malawi, Mozambique, Zambia, and Zimbabwe. In Imbokodo, researchers are studying whether the vaccine regimen that showed the most immunogenicity in the APPROACH study is actually protective against HIV infection. A total of 2,600 sexually-active women ages eighteen to thirty-five are currently being enrolled in the study. (This column covered the Imbokodo study in the March 2018 issue.)

Participants will be given four doses of the prime vaccine and two boosters over a twelve-month period. The results of the Imbokodo study are expected in 2021.

Data on the APPROACH study collected one month after the last vaccination, was published online by The Lancet on July 6, 2018. The long-term data—one year after the last vaccination—was presented at the 22nd International AIDS Conference (AIDS 2018) in Amsterdam, also in July.

Commenting on the latest results, Janssen’s head of Viral Vaccines programs, Hanneke Schuitemaker, said: “This is one of the only times that long-term immune response data for a candidate HIV vaccine have been presented. We will need to see if the Imbokodo study confirms the potential observed in the APPROACH study, but we are cautiously optimistic. The world urgently needs an effective preventive HIV vaccine, and we hope that we are finally on the road to achieving this goal!”


Jeannie Wraight is the former editor-in-chief and co-founder of HIV and HCV Haven (www.hivhaven.com) and a blogger and writer for TheBody.com. She is a member of the Board of Directors of Health People, a community-based organization in the South Bronx and an advisor to TRW (Teach me to Read and Write), a community-based organization in Kampala, Uganda. She lives with her husband in New York City.