A novel combination treatment may increase the ability of monoclonal antibodies to control viral infection in patients diagnosed with HIV, according to a Northwestern Medicine study published in Science Translational Medicine.
This really demonstrates that that we should combine broadly neutralizing antibodies with other immunostimulatory agents, especially those that may impact immune response. If we want to use broadly neutralizing antibodies to cure, we need to find the right combination."
Elena Martinelli, PhD, MPH, research professor of Cell and Developmental Biology and senior author of the study
Neutralizing antibodies, a key component of the body's adaptive immune response in fighting against viruses and other pathogens, bind to the surface of infected cells and inhibit them from interacting with and infecting healthy host cells. Previous research has shown that these broadly neutralizing antibodies can promote the body's immune response, specifically by increasing T-cell and antibody responses in patients diagnosed with HIV.
Additionally, past research efforts led by Martinelli discovered that cells which express the cellular receptor Integrin alpha 4 beta 7 are more commonly infected by HIV and promote pathogenesis. Understanding exactly how an individual's immune response reacts in the presence of neutralizing antibodies is essential to developing novel therapeutic interventions for treating HIV, according to Martinelli.
For the current study, investigators administered anti-HIV broadly neutralizing antibodies (bNAbs) or a combination of bNAbs and an anti-alpha 4 beta 7 monoclonal antibody in animal models of HIV-infection.
Overall, the combination therapy group demonstrated lower viral load — the amount of a virus present in bodily fluids — until the end of the study's follow-up period compared to the group that received bNAbs alone.
The study underscores the therapeutic potential in using a combination of neutralizing antibodies and immunostimulatory agents to increase immune response for patients with HIV, according to Martinelli. As for next steps, Martinelli said it will be essential to study the combination treatment administered in additional models of HIV-infection that also received HIV antiretroviral therapy.
"There is a lot of work right now trying to make these antibodies more potent and make them last longer, which is great, but I also think there is space to improve the functionality of these antibodies by combining them with other immunostimulatory agents," Martinelli said.
Thomas Hope, PhD, professor of Cell and Developmental Biology, of Obstetrics and Gynecology and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, was a co-author of the study.
Frank, I., et al. (2021) Blocking α4β7 integrin delays viral rebound in SHIVSF162P3-infected macaques treated with anti-HIV broadly neutralizing antibodies. Science Translational Medicine. doi.org/10.1126/scitranslmed.abf7201.