Newly defined biomarker may accelerate clinical trials for vaccines to prevent HIV-1 infection.
A study published in August 22, 2022, issue of Nature Medicine identifies a new biomarker that appears effective as a surrogate endpoint to reliably predict the ability of broadly neutralizing monoclonal antibodies to prevent acquisition of HIV-1, the most common type of the virus that causes AIDS.
Broadly neutralizing antibodies (bnAbs) are defined by their ability to neutralize multiple genetically distinct viral strains.
Findings from this study build on the proof-of-concept Antibody Mediated Prevention (AMP) trials published in March 2021 showing that a bnAb called VRC01 was effective in preventing the acquisition of some, but not all, HIV strains.
Seventy percent of strains circulating in regions where the studies were conducted sub-Saharan Africa, the U.S. and South America, were resistant to VRC01, and the original report noted no statistical difference between the VRC01 arms and the placebo arm in overall prevention of HIV acquisition.
“A single HIV-1 broadly neutralizing monoclonal antibody, such as VRC01, will not be sufficient to provide high protection against HIV-1 acquisition because many strains are resistant. Therefore, bnAb cocktails will be needed, and although there is a rich pipeline of these antibodies under development, we first needed a biomarker that would enable us to compare cocktails and select the best candidates to advance to efficacy trials,” said Dr. Peter Gilbert, one of the paper’s co-first authors. He and co-first author Dr. Yunda Huang are researchers with the HIV Vaccine Trials Network (HVTN), based at Fred Hutchinson Cancer Center in Seattle.
The study was conducted with collaborators from the HIV Prevention Trials Network (HPTN), based at FHI 360, Durham, North Carolina.
Gilbert said a useful biomarker must also be validated as a surrogate endpoint to reliably predict the prevention efficacy level of an HIV-1 bnAb cocktail. This would permit expedited approval of different cocktails without requiring long and expensive efficacy trials. According to results from this study, the newly defined biomarker, called PT80, appears to meet those requirements, which predicts the 80% neutralizing antibody titer of a bnAb recipient’s blood sample at a given time to a given virus.
“In other words, PT80 quantifies the ‘killing power’ of a bnAb in a blood sample at a given time point against a specific HIV-1 strain,” said Dr. Larry Corey, AMP Protocol Chair and Principal Investigator, HVTN Leadership Operations Center. “Our study showed that PT80 is likely to be highly successful as the sought-after biomarker and surrogate endpoint for future monoclonal antibody studies.”
The HVTN and HPTN expect to leverage these study results in planning and seeking approval for an AMP-sequel, large-scale efficacy study.