So far, HIV has killed 40 million people worldwide and infected 37 million 600 thousand people. In order to end the HIV / AIDS epidemic, scientists have been looking for effective vaccines or treatments. However, due to the diversity of HIV-1 and the long hidden potential challenges, there is still no successful treatment.
In August 27, 2021, a multi agency research group led by the AIDS Research Institute of University of Hong Kong School of medicine and Microbiology Department published a research article entitled "Tandem bispecific antibody prevents pathogenic SHIVSF162P3CN infection and disease disease" on Cell Reports.
1) Intravenous injection of shivsf162p3cn can lead to high mortality of Chinese macaques; 2) BIIA SG injection before infection can prevent shivsf162p3cn infection; 3) BIIA SG injection after infection transformed pathogenic infection into long-term viremia control.
Source: cell reports
What is BIIA SG?
BIIA SG is a bispecific antibody, including four scFv binding domains, including two HIV-1 gp120 binding domains and two CD4 binding domains. BIIA SG can inhibit T cells and key targets on the surface of HIV virus at the same time. On the one hand, it can prevent immune cells from being destroyed, on the other hand, it can prevent the replication and transmission of HIV virus in vivo.
The experiment showed that BIIA SG neutralized all 124 tested HIV-1 Pseudoviruses, including global subtype / recombinant form, transmitted virus / founding virus, variants insensitive to parental bNAb and many other bNAb, with an average IC50 value of 0.073 & mu; g/ml。
Source: J Clin invest
BIIA SG is effective in non-human primates
In order to study the role of BIIA SG in non-human primates, the researchers explored the therapeutic effects of BIIA SG under two methods of use (preventive injection of BIIA SG and BIIA SG). After inoculating 6 CRMs with 10 mg / kg BIIA SG by intramuscular injection or intravenous injection for 24 hours, HIV infection was induced by intravenous injection of shivsf162p3cn. The results showed that all rhesus monkeys pretreated with BIIA SG were not infected.
Next, the researchers tried to investigate whether BIIA SG monotherapy prevented latency establishment and shivsf162p3cn infection after 1 DPI (days after infection) and 3 DPI. After intravenous injection of shivsf162p3cn, 7 CRMs in group C were intramuscularly injected at 1 DPI and 6 CRMs in group D were intramuscularly injected at 3 DPI. Single dose BIIA SG treatment saved 13 (100%) CRM from death and had a significant survival advantage, and 61.5% of 8 patients became undetectable plasma viral load at about 84 DPI, including 5 of 7 in group C (71.4%) and 3 of 6 in group D (50%).
Source: cell reports
BIIA SG still has problems to be studied
Although BIIA SG has shown significant effects in non-human primates, its effect in human application is still unknown, especially the problem of short half-life. The researchers pointed out that the short half-life time in CRM may be related to the relatively rapid response of ADA. When BIIA SG is tested in human trials, this problem may be alleviated because it is designed as a bispecific antibody of higg FC.
At the same time, the researchers proposed that two amino acid substitutes, lysine serine (LS) mutation (m428l and n434s mutation), could be introduced into the Fc fragment of BIIA SG, which could not only prolong the half-life, but also improve its distribution in intestinal mucosa.
The combined antiretroviral therapy (cART) introduced in 1995 greatly reduced AIDS related mortality. However, because cART needs life-long treatment, the cost of treatment is still an unsustainable economic burden for 37 million 600 thousand of the HIV infected people in addition to the increasing incidence of drug toxicity and the accumulation of drug-resistant viruses. Under such circumstances, the research and development of BiIA-SG will bring new hope to people living with HIV.
Source: Frontier of life science
 https://www.cell.com/cell-reports/fulltext/S2211-1247 (21)01049-4#bib61
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