HIV Monoclonal Antibody Studies

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications, trials & patents

Abstract

With a goal of improving the ability of anti-HIV monoclonal antibodies to neutralize the human immunodeficiency virus (HIV), Vaccine Research Center (VRC) scientists developed a bispecific monoclonal antibody that binds to two different regions of the HIV-1 envelope glycoprotein, a main target of the immune response to HIV. This bispecific antibody contains a llama nanobody that is linked to the light chain of an HIV antibody. The nanobody binds to the CD4 binding site of the HIV envelope trimer and the other component of the antibody binds to the V2 region of the HIV trimer. In preclinical studies, this bispecific antibody neutralized a greater number of HIV strains and was more potent compared to either of its components alone. The VRC Clinical Trials Program (CTP) conducted a phase 1, first-in-human, clinical trial (NCT06585891) that evaluated that safety, tolerability, and pharmacokinetics of this novel bispecific monoclonal antibody administered to healthy volunteers 18 to 60 years of age. Exploratory objectives include assessment of the neutralization activity of the antibody in serum and determining whether study participants developed anti-drug antibody against the monoclonal antibody. Data analysis is ongoing. The VRC CTP published the results of a phase 1 clinical trial, VRC 609 (NCT03538626), that evaluated a monoclonal antibody targeting the CD4-binding site of the HIV-1 envelope trimer in healthy volunteers 18 to 50 years of age. For one group of study participants, the antibody was combined with a permeation-enhancing product. This was the first study that combined an anti-HIV monoclonal antibody with the permeation-enhancing product to enable the administration of higher doses and larger volumes of antibody subcutaneously. The monoclonal antibody was found to be safe and tolerable and had a serum half-life that was as good as or better than that of other HIV antibodies targeting the CD4-binding site. In this first-in-human study, the addition of the permeation-enhancing product was safe and tolerable and demonstrated another method that can be used safely to administer HIV monoclonal antibodies.