A research team led by scientists at the University of Hong Kong’s (HKU) AIDS Institute and Department of Microbiology have created a universal antibody which targets all strains of HIV/AIDS, including genetically divergent forms.
The scientists created the drug, an encoded tandem bispecific immunoadhesin molecule (BiIA) called BiIA-SG, by engineering a bi-specific neutralising antibody. In studies it showed efficacy in eliminating latently infected cells in a humanised mouse model, as well as in all genetically divergent global HIV-1 strains.
BilA-SG attaches to the host protein CD4 and attacks invading HIV-1 particles to protect CD4 positive T-cells. Of the 124 genetically divergent global HIV-1 strains examined, BilA-SG demonstrated potent activity against all of them, as well as inhibiting diverse live viral challenges in humanised mice.
In addition, gene transfer of BilA-SG achieved prolonged drug availability in vivo, implying its potential efficacy in eliminating HIV-1 infected cells in humanised mice. As such, the team provides proof-of-concept that BilA-SG offers a novel, universal antibody drug for the prevention of and immunotherapy against HIV-1 infection.
Globally, the HIV/AIDS virus has caused approximately 40 million deaths, with around 36.9 million people still living with the condition. Finding an effective cure has been previously hindered due to the variety of HIV-1 forms and the antiviral drug-unreachable latency, making it near impossible to create an immunogen which could target genetically diverse HIV-1 subtypes. As such, developing existing broadly neutralizing antibodies (bnAbs) as passive immunisation has been an increasingly popular method for HIV-1 prophylaxis and immunotherapy.
Previously the potency, breadth and crystal structure of bnAbs have been examined both in vitro and in vivo. Naturally occurring HIV-1 resistant strains are found against these bnAbs and often result in the failure of durable viral suppression in bnAb-based monotherapy.
Specially engineered bi-specific bnAb blocks two steps of HIV-1 entry into target cells and has previously shown efficacy in animal models. Prior to the publication of this study, tandem bi-specific bnAb had not been investigated in vivo against HIV-1 infection.
Findings were published in the April edition of Journal of Clinical Investigation.