On World AIDS Day: Scientists Developed Antibodies for HIV Treatment

HIV (human immunodeficiency virus) is a virus that targets the immune system, primarily CD4 cells and T cells. If HIV infection is not treated, it can progress to AIDS (acquired immunodeficiency syndrome), a late stage of HIV infection in which the immune system is irrevocably destroyed. Since the beginning of the disease, an estimated 38 million individuals worldwide have been diagnosed with HIV, and tens of millions have died from AIDS.

December 1st, 2021 is World AIDS Day with the theme "End inequalities. End AIDS". As HIV remains a major issue affecting millions of people worldwide, the research of discovering novel treatment has never stopped. Significant improvements in treatment for people living with HIV have yielded substantial improvements in global health as a result of the unique benefits of antiretroviral therapy (ART), which averted 9.5 million deaths worldwide in 1995-2015, with global economic benefits of $1.05 trillion. Despite the fact that ART can help manage HIV, there is no therapeutic cure that can completely eliminate the virus from infected people.

According to a new study published on Sept. 28, 2021, in mBio, researchers at the Uniformed Services University of the Health Sciences (USU) and Université de Montréal, Canada, have discovered a way to potentially eliminate HIV-1 infection in infected individuals by using a new type of antibody-based therapeutic.

Dr. Marzena Pazgier from the USU Department of Medicine's Infectious Diseases Division and Dr. Andrés Finzi from the Université de Montréal's affiliated teaching hospital research center led the study, titled "Across functional boundaries: making non-neutralizing antibodies to neutralize HIV-1 and mediate Fc-mediated effector killing of infected cells".

The researchers focused on antibodies against HIV-1 in this study, particularly focusing on non-neutralizing antibodies, which are created naturally as part of the immune system's response. The very vulnerable sites on the virus that may be detected by non-neutralizing antibody types are hidden in people of HIV-1 infected, and hence cannot be employed for therapeutic treatments.

The researchers created novel antibody molecules known as Ab-CD4 hybrids that can circumvent this barrier by disclosing previously concealed sites. This allows them to not only kill the virus, but also to remove infected cells, which are creating thousands of infectious viral particles.

These Ab-CD4 hybrids are created by attaching a non-neutralizing antibody to a region of the virus's primary receptor for entry into a CD4 molecule. When the antibody and the CD4 molecule are linked, they work together to reveal the virus's secret targets, allowing for efficient anti-viral activities. When evaluated for anti-HIV activity, the Ab-CD4 hybrids directly neutralize various strains of HIV-1 and then kill HIV-1 infected cells with host immune cells, such as natural killer cells.

"This represents a new family of potent ‘weapons’in the growing arsenal being built to achieve an HIV-1 cure," Pazgier introduced. These novel compounds get the capacity to kill HIV-1-infected cells in a live organism by compelling the virus to disclose its susceptible spots, she noted and hoped that with this new breakthrough, HIV-1 infected people will get benefits from this in the future.

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