Broadly neutralizing antibodies aim for a diverse effect against HIV types
by Jeannie Wraight and David Miller
Broadly neutralizing antibodies (bNAbs) hold the potential of being a component of an HIV functional cure regimen, an HIV treatment, and even a prevention therapy to protect against the virus. Several bNAbs are in development which could offer new hope to those for who current ARVs are not optimal. Research reported in the May edition of the journal Cell discussed one novel bNAb approach.
The antibodies of most people living with HIV are only able to target one particular strain. Approximately ninety percent of people living with HIV have viruses that belong to the HIV-1 Group M, which is further broken down into subtypes, or clades, named A–K. In the U.S. and Europe, most people living with HIV have Clade B viruses. Antibodies are normally only active against one clade. However, researchers from the Institute of Human Virology at the University of Maryland School of Medicine along with researchers at Harvard and a biotechnology company called Atreca, recently identified monoclonal antibodies that appear capable of a broadly neutralizing effect on a diverse range of HIV subtypes.
A technology, called the Immune Repertoire Capture (IRC) platform was used to sequence antibodies taken from the blood and antibody-producing cells in the bone marrow of elite neutralizers, individuals with HIV who are capable of producing antibodies effective against numerous HIV strains.
A family of antibodies were found from one individual that were active against eighty-nine to 100 percent of 117 subtypes of HIV, more than any other broadly neutralizing antibodies previously discovered.
The most promising bNAbs of the group will be identified and engineered for the strongest possible response. According to Chief Technical Officer at Atreca and co-author of the Cell article, Guy Cavet, PhD, “Antibodies come from families. Each includes a set of related antibodies that come from a common ancestor. They all have something in common; they bind to the HIV envelope in the same way, but they have different levels of activity so we want to find the best members of that family and make deliberate modifications to make them perform better.”
The specific bNAbs discussed in the Cell article will potentially be studied as an HIV therapy. Mohammad Sajadi, MD, Associate Professor of Medicine at the Institute of Virology and lead author of the Cell article, suggests such a therapeutic would need to be administered at a minimum of once every several months. Dr. Sajadi notes, “bNAbs, in some form, could be useful as prophylaxis against HIV as an alternative to a vaccine.” In addition. bNAbs could provide an option for those who are not able to maintain complete viral suppression or who are unable to tolerate daily ARVs.
As bNAbs target the HIV envelope, a different site than any of the FDA-approved HIV antivirals, a potential bNAb could be active against viruses that are resistant to current therapies, so HIV mutations that inevitably arise over the duration of ARV treatment will predictably not evade suppression. Further, because bNAbs also offer new promise for treatment-experienced, drug-resistant patients, due to a distinct mechanism of action from other therapies, fast-tracking bNAb drugs for those with limited clinical options is feasible.
In addition to treatment, bNAbs are also being researched as components of potential HIV cure strategies. Although bNAbs are not able to awaken latent HIV, which is currently the main barrier in cure research, they could be used in combination with other therapeutic agents that elicit a response from latent cells causing them to express viral proteins which would alert bNAbs to their presence. bNAbs could then drive the killing of these infected cells, possibly reaching cells that ARVs cannot.
HIV replicates and mutates very quickly. Because of this there is a high diversity amoung strians of HIV. This makes developing an HIV vaccine that is effective against all HIV strains across the globe very difficult. A vaccine that can elicit a broadly neutralizing effect is needed for a vaccine to be fully effecive for everyone. bNAbs are being considered in vaccine research for just this reason.
As funding becomes available, plans are for a lead bNAb candidate discovered through the IRC platform to move forward into pre-clinical testing with hopes of initiating an IND for a Phase I study in approximately two years.
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.
David Miller is a long-term survivor and a veteran of ACT UP NY. He has been a member of the Bronx HIV CARE Network, the NYC HIV Planning Council Advisory Group and served on the Board of The AIDS Institute. He now lives in upstate New York, where he serves on the University of Rochester ACTG CAB.