BilA-SG bi-specific antibody shows potential in HIV-1 prophylaxis and treatment

Injection of the bi-specific broadly neutralizing antibody (bi-bNAb), BilA-SG, is effective as pre-exposure prophylaxis and postexposure treatment against HIV-1, according to results of an immunology study by researchers from the University of Hong Kong (HKU). 

“Although results of bNAb combination immunotherapies against various simian-HIV [SHIV] strains have been promising in preclinical and clinical settings, few bi-bNAbs have been evaluated against SHIV strains in nonhuman primate [NHP] studies,” said the authors. [Cell Rep 2021;36:109611]

“Our team previously reported the role of BiIA-SG in preventing a diverse range of HIV-1 infections and in eliminating infected cells by adeno-associated virus [AAV]–immunotherapy in some humanized mice. However, clinical application of the study results was limited by the short lifespan of mice and lack of host immunity,” explained the authors.

“This is the first study to assess the prophylactic and immunotherapeutic efficacy of bi-bNAb against pathogenic SHIV_SF162P3CN, a Chinese-origin rhesus macaque [CRM]–adapted tier-2 R5-tropic challenge strain, in [a total of 27] CRMs,” they said.

“Our study showed benefits of BilA-SG for both pre-exposure prophylaxis and postexposure treatment of HIV-1. Given the feasibility of mass production of BilA-SG under good manufacturing practice [GMP] conditions, our findings support clinical development of BilA-SG for pre-exposure prophylaxis of HIV-1 and immunotherapeutic treatment of AIDS following exposure to HIV-1,” they suggested.

Engineered BilA-SG displayed potent anti-SHIV_SF162P3CN activity in ex vivo studies. Intramuscular (IM) BilA-SG injection was shown to be practical, with content widely distributed from site of administration to lymphatic drainage and peripheral bloodstream.

Persistently high level of viraemia and mortality rate were shown in the majority (six out of eight; 75 percent) of CRMs after high-dose intravenous (IV) challenge with pathogenic SHIV_SF162P3CN, with a drop in CD4/CD8 ratio and development of diarrhoea, anorexia and weight loss, followed by death. Anti–HIV-1_SF162 glycoprotein (gp) 120 humoral response was displayed in only two surviving CRMs after 42 days postinfection (dpi).

Both IM and IV BiIA-SG injection (10 mg/kg) were effective in conferring protection against IV SHIV_SF162P3CN challenge in all CRMs (n=6), with undetectable plasma viral RNA load, proviral DNA load and humoral responses and T-cell response against Gag and Nef, as well as stabilization of CD4/CD8 ratio achieved at 28 dpi.

A single BiIA-SG (20 mg/kg) IM injection, at 1 dpi and 3 dpi, was also effective in reducing peak viraemia and achieving undetectable setpoint viraemia, and in delaying disease progression, with a 2-year survival rate of 100 percent. Plasma viral RNA load and CD4/CD8 ratio stabilized after reaching peak viraemia. None of the treated CRMs had diarrhoea, weight loss, significant CD4 lymphocytopenia, or progression to death. Undetectable viral load was maintained (at around 84 dpi) in 61.5 percent of treated CRMs.

Postexposure treatment with a single BilA-G injection induced development of CD8+ T cells for durable viral suppression and triggered germline NAb response against IV SHIV_SF162P3CN challenge in eight out of 13 CRMs, as determined by anti-CD8β monoclonal antibody depletion experiments and plasma neutralizing activities.

“Besides BilA-SG vaccination, our team also showed that programmed death-1 [PD-1]–based vaccination induced sustained viral suppression by memory CD8+ T cells,” said Professor Zhiwei Chen of the Department of Microbiology, HKU. [PLoS Pathog 2021;17:e1009647] “By developing BiIA-SG–based and PD-1–based vaccination for clinical use against AIDS, we aspire to generate the first made-in-Hong Kong immunotherapy to provide functional cure for AIDS.”