Team invents universal antibody drug for HIV-1 prevention and immunotherapy

May 8, 2018, The University of Hong Kong
A research team led by scientists at AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine of The University of Hong Kong (HKU) invents a universal antibody drug against HIV/AIDS, and the new findings are published in the April issue of Journal of Clinical Investigation. Credit: The University of Hong Kong

A research team led by scientists at AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine of The University of Hong Kong (HKU) invents a universal antibody drug against HIV/AIDS. By engineering a tandem bi-specific broadly neutralizing antibody, the team found that this novel antibody drug is universally effective not only against all genetically divergent global HIV-1 strains tested but also promoting the elimination of latently infected cells in a humanized mouse model. The new findings are now published in the April issue of Journal of Clinical Investigation.

Background

AIDS remains an incurable disease. In the world, HIV/AIDS has resulted in estimated 40 million deaths while 36.9 million people are still living with the virus. To end the HIV/AIDS pandemic, it is important to discover either an effective vaccine or a therapeutic cure. There are, however, two major scientific challenges: the tremendous HIV-1 diversity and the antiviral drug-unreachable latency. Since it is extremely difficult to develop an appropriate immunogen to elicit broadly neutralizing (bnAbs) against genetically divergent HIV-1 subtypes, developing existing bnAbs as passive immunization becomes a useful approach for HIV-1 prophylaxis and immunotherapy.

Previous studies have investigated the potency, breadth and crystal structure of many bnAbs including their combination both in vitro and in vivo. Naturally occurring HIV-1 resistant strains, however, are readily found against these so-called bnAbs and result in the failure of durable viral suppression in bnAb-based monotherapy. To improve HIV-1 neutralization breadth and potency, bispecific bnAb, which blocks two essential steps of HIV-1 entry into target cells, have been engineered and show promising efficacy in animal models. Before the publication, tandem bi-specific bnAb has not been previously investigated in vivo against HIV-1 infection.

Research method and findings

The HKU research team invented a single gene-encoded tandem broadly neutralizing antibody, titled "BiIA-SG", which "kills two birds with one stone". By attaching to host protein CD4, BiIA-SG strategically ambushes invading HIV-1 particles to protect CD4 positive T cells. BiIA-SG not only displays a potent activity against all three panels of 124 genetically divergent global HIV-1 strains tested, but also prevents diverse live viral challenges completely in humanized mice. Moreover, gene transfer of BiIA-SG achieves pro-longed drug availability in vivo, leading to a promising efficacy of eliminating HIV-1 infected cells in humanized mice. Therefore, the research team provides a proof-of-concept that BiIA-SG is a novel universal antibody drug for prevention and immunotherapy against HIV-1 infection.

Significance of the study

The accumulated number of HIV-1 infections has more than doubled from 4,443 diagnostic cases in 2009 to 9,091 in 2017, despite the timely introduced combination antiretroviral therapy and prevention interventions in Hong Kong. Currently, the estimated annual cost is over HK$550 millions for antiretroviral drugs alone per year in Hong Kong, not to mention the rising issues of life-long financial burdens, drug toxicity and resistant viruses. The newly invented universal antibody drug brings the hope to fight these issues. With significantly improved breadth and potency, BiIA-SG will hopefully be the first "Made in Hong Kong" anti-HIV-1 antibody for clinical development.

Explore further: Genetically altered broadly neutralizing antibodies protect monkeys from HIV-like virus

More information: Xilin Wu et al. Tandem bispecific neutralizing antibody eliminates HIV-1 infection in humanized mice, Journal of Clinical Investigation (2018). DOI: 10.1172/JCI96764

Related Stories

Genetically altered broadly neutralizing antibodies protect monkeys from HIV-like virus

April 16, 2018
Two genetically modified broadly neutralizing antibodies (bNAbs) protected rhesus macaques from an HIV-like virus, report scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National ...

Antibodies show effectiveness for HIV prevention and promise for treatment and cure

January 17, 2018
The ability of HIV to mutate has been a major challenge to vaccine development. As the body produces antibodies to target the outer HIV envelope protein, this protein changes, thwarting the circulating antibodies' ability ...

New findings to help HIV scientists establish 'template' for potent antibodies

November 21, 2017
New data published today in Immunity further illuminate how some human beings generate powerful, HIV-blocking antibodies. Led by scientists at the International AIDS Vaccine Initiative (IAVI) and The Scripps Research Institute ...

Broadly neutralizing HIV antibodies engineered to be better vaccine leads

August 25, 2016
One approach to HIV vaccine development relies on broadly neutralizing antibodies (bnAbs) that protect against different circulating HIV strains. bnAbs have been isolated from HIV-infected individuals, but they are highly ...

An antibody that can attack HIV in new ways

September 11, 2015
Proteins called broadly neutralizing antibodies (bNAbs) are a promising key to the prevention of infection by HIV, the virus that causes AIDS. bNAbs have been found in blood samples from some HIV patients whose immune systems ...

Mechanism found for development of protective HIV antibodies

July 24, 2014
Scientists at Duke Medicine have found an immunologic mechanism that makes broadly neutralizing antibodies in people who are HIV-1 infected.

Recommended for you

New HIV therapy reduces virus, boosts immunity in drug-resistant patients

August 15, 2018
In a study, a new HIV drug reduced viral replication and increased immune cells in individuals with advanced, drug-resistant HIV infection. Used in combination with existing HIV medications, the drug is a promising strategy ...

In choosing care, HIV patients in Zambia prefer kindness over convenience

August 15, 2018
As a healthcare patient, what would you sacrifice for a provider with a nice—rather than rude—attitude? For HIV patients in Zambia, the answer may surprise you.

Details of HIV-1 structure open door for potential therapies

August 9, 2018
New research provides details of how the structure of the HIV-1 virus is assembled, findings that offer potential new targets for treatment.

Researchers uncover potential new drug targets in the fight against HIV

August 7, 2018
Johns Hopkins scientists report they have identified two potential new drug targets for the treatment of HIV. The finding is from results of a small, preliminary study of 19 people infected with both HIV—the virus that ...

Naltrexone helps HIV positive individuals reduce heavy alcohol use

August 7, 2018
Extended-release naltrexone—an injection that decreases heavy drinking in the general population when taken in conjunction with counseling—appears to help HIV-positive individuals reduce their number of heavy drinking ...

EU door opens for generic version of AIDS medicine Truvada

July 26, 2018
Patient associations on Thursday lauded an EU decision to allow the sale of generic versions of Truvada, an anti-retroviral medicine used by those diagnosed HIV-positive, the virus causing AIDS.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.