After 40 years, researchers discover new frontiers in the fight against HIV

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On July 3, 1981, Rick Springfield was pining for “Jessie’s Girl,” Lady Diana was preparing to tie the knot, and Sandra Day O’Connor was on her way to becoming the first woman to sit on the Supreme Court. It was also the day the first major reporting on what is now known as HIV and AIDS appeared in a major media outlet: The headline “Rare cancer seen in 41 homosexuals” was buried deep in The New York Times.

Since then, researchers and doctors have put forth great effort to understand and treat patients with HIV. We now know it isn’t a form of cancer, but rather a virus that inserts itself into the DNA of a human host and attacks the body’s immune system. Antiretroviral therapies have allowed many with the virus to live longer, healthier lives. Yet, a widely available cure or vaccine to prevent infection have remained elusive.

The virus is a particularly wily opponent — it commandeers the very immune cells responsible for destroying it. So Despite these advances only one out of the seven HIV vaccine candidates that have completed efficacy trials has shown modest successsays Dagna Laufer, vice president of clinical development at IAVI, a nonprofit infectious disease research organization.

But defeats of the past are lessons learned, Laufer says. Over the past two decades, advances in the immunology and gene editing fields have breathed new life into HIV research and marked a potential turning point in the mission to end the disease.

IAVI vice president and head of clinical development Dagna Laufer

Permission granted by IAVI.

“We’re in a new era and a very exciting time for HIV vaccine development,” Laufer says. “If you looked at an immunology textbook 10 years ago, it wouldn’t even look like what’s happening today. The HIV field has gone through so much advancement in terms of techniques and tools, it’s just incredible.”

As researchers head into this new chapter, we’re examining two companies with technologies that tackle the issue from different angles — one aims to prevent infections and the other hopes to cure existing cases — both with the goal of ending the virus’ 40-year scourge.

The search for a vaccine

IAVI is a series of iterative clinical trials Designed to test whether the administration of HIV immunogens can stimulate the immune system’s B cells to begin developing antibodies, known as broadly neutralizing antibodies (bNABs), that can defeat many different variants of HIV.

IAVI began the G002 phase 1 trial in January with partner Moderna. The vaccine candidate uses engineered HIV envelope proteins delivered via mRNA, building on a previous trial called IAVI G001, in which the vaccine delivered the same material through a protein and showed initial positive results.

Laufer says the hope is that using mRNA as the delivery vehicle in this trial will allow IAVI to speed up production of the materials while yielding similar results to G001.

“If you looked at an immunology textbook 10 years ago, it wouldn’t even look like what’s happening today. The HIV field has gone through so much advancement in terms of techniques and tools, it’s just incredible.”

Dagna Laufer

IAVI vice president and head of clinical development

As the vaccine development program progresses, the team will deliver sequential booster shots to participants that they hope will slowly teach the body to create the antibodies. Laufer says it’s unclear how many different boosters will need to be administered and emphasizes that the candidate is not along the product development path yet.

“You just don’t go from one to 10 or, A to Z,” she says. “We don’t expect to have a vaccine in the next year or even maybe in the next 10 years. But we know that it is going to take a while to figure out what the steps are.”

The approach is based on a series of studies from 2009 which found that some HIV patients naturally develop bNABs, Laufer says, adding that this process takes many years and, by the time they are created, it’s often too late for the patient. IAVI’s candidate would provide vaccine immunogens to kickstart the development of bNABs in the body long before an HIV infection occurs.

The nonprofit is also sponsoring several other vaccine trials including one Looking at an engineered trimeric protein immunogen and another Focused on T-cell responses led by the Globally Relevant AIDS Vaccine Europe-Africa Trials Partnership (GREAT).

“We will support and hope that all of the researchers come through because that’s really the only way that we’re actually going to be able to end this [epidemic],” Laufer says. “I think that vaccines are the nail in the coffin, but we really understand that there are so many ways to deal with this virus.”

A potential cure

While the hunt for a vaccine continues, Excision BioTherapeutics, a clinical-stage biotech company, thinks it’s found a treatment pathway for HIV with a gene-editing candidate it says could be a “one-time curative treatment option.

Excision BioTherapeutics’ CEO Daniel Dornbusch

Permission granted by Excision BioTherapeutics.

That candidate, EBT-101, is a CRISPR-based therapy designed to remove large sections of the HIV DNA that takes over a patient’s cells. The technology has so far demonstrated the first and only cure in mice and primate forms of HIV and a phase 1/2 human trial is set to begin in the next few weeks.

Excision CEO, Daniel Dornbusch, says the company’s platform technology, which employs CRISPR-Cas9 and dual guide RNAs, minimizes the potential for vaccine mutation and off-target effects.

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