Engineered immune cells elicit broad response to HIV in mice, offering hope for vaccine

November 19, 2020

LA JOLLA, CA--Unlike so many other deadly viruses, HIV still lacks a vaccine. The virus--which continues to infect millions around the world--has proven especially tricky to prevent with conventional antibodies, in part because it evolves so rapidly in the body. Any solution would require coaxing the body into producing a special type of antibody that can act broadly to defeat multiple strains of the virus at once.

This week, scientists at
In experiments involving mice, the approach successfully induced broadly neutralizing antibodies--also called bnabs--that can prevent HIV infection, says principal investigator James Voss, PhD, of Scripps Research. The study appears in Nature Communications.

Voss and his team showed in 2019 that it was possible to reprogram the antibody genes of the immune system's B cells using CRISPR so the cells would produce the same broadly neutralizing HIV antibodies that have been found in rare HIV patients.

The new study shows that such engineered B cells, after being reintroduced to the body, can multiply in response to a vaccination--and mature into memory cells and plasma cells that produce high levels of protective antibodies for long periods of time in the body. The team also demonstrated that the engineered genes can be improved to make antibodies that are even more effective against the virus, using a process that normally occurs in B cells that are responding to immunization.

"This is the first time it has been shown that modified B cells can create a durable engineered antibody response in a relevant animal model," Voss explains.

He hopes that his vaccine approach may someday prevent new HIV infections and possibly offer a functional cure to those who already have HIV/AIDS. The virus is still prevalent throughout the world, with an estimated 38 million people with the disease in 2019.

Voss notes that in humans, the starting cells to create the vaccine could be obtained easily from a simple blood draw, then engineered in the lab before being reintroduced to the patient. He and his team--including first author Deli Huang, PhD, Jenny Tran, PhD, Alex Olson, PhD, and graduate student Mary Tenuta--are now exploring ways to improve the technology so that it would be accessible to the greatest number of people. Because the approach relies on delivering genes to a patient's own immune cells, this could be a significant challenge.

"People think of cell therapies as being very expensive," Voss says. "We're doing a lot of work towards trying to make the technology affordable as a preventative HIV vaccine or functional cure that would replace daily antiviral therapy."
The study, "Vaccine elicitation of HIV broadly neutralizing antibodies from engineered B cells," was authored by Deli Huang, Jenny Tuyet Tran, Alex Olson, Thomas Vollbrecht, Mary Tenuta, Mariia Guryleva, Roberta Fuller, Torben Schiffner, Justin Abadejos, Lauren Couvrette, Tanya Blane, Karen Saye, Wenjuan Li, Elise Landais, Alicia Gonzalez-Martin, William Schief, Ben Murrell, Dennis Burton, David Nemazee and James Voss.

The work was supported by the Bill and Melinda Gates Foundation (OPP1183956) and the National Institutes of Health (5R01DE025167?05, R01AI128836 and R01AI073148).

Scripps Research Institute

Related HIV Articles from Brightsurf:

BEAT-HIV Delaney collaboratory issues recommendations measuring persistent HIV reservoirs
Spearheaded by Wistar scientists, top worldwide HIV researchers from the BEAT-HIV Martin Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy (BEAT-HIV Collaboratory) compiled the first comprehensive set of recommendations on how to best measure the size of persistent HIV reservoirs during cure-directed clinical studies.

The Lancet HIV: Study suggests a second patient has been cured of HIV
A study of the second HIV patient to undergo successful stem cell transplantation from donors with a HIV-resistant gene, finds that there was no active viral infection in the patient's blood 30 months after they stopped anti-retroviral therapy, according to a case report published in The Lancet HIV journal and presented at CROI (Conference on Retroviruses and Opportunistic Infections).

Children with HIV score below HIV-negative peers in cognitive, motor function tests
Children who acquired HIV in utero or during birth or breastfeeding did not perform as well as their peers who do not have HIV on tests measuring cognitive ability, motor function and attention, according to a report published online today in Clinical Infectious Diseases.

Efforts to end the HIV epidemic must not ignore people already living with HIV
Efforts to prevent new HIV transmissions in the US must be accompanied by addressing HIV-associated comorbidities to improve the health of people already living with HIV, NIH experts assert in the third of a series of JAMA commentaries.

The Lancet HIV: Severe anti-LGBT legislations associated with lower testing and awareness of HIV in African countries
This first systematic review to investigate HIV testing, treatment and viral suppression in men who have sex with men in Africa finds that among the most recent studies (conducted after 2011) only half of men have been tested for HIV in the past 12 months.

The Lancet HIV: Tenfold increase in number of adolescents on HIV treatment in South Africa since 2010, but many still untreated
A new study of more than 700,000 one to 19-year olds being treated for HIV infection suggests a ten-fold increase in the number of adolescents aged 15 to 19 receiving HIV treatment in South Africa, according to results published in The Lancet HIV journal.

Starting HIV treatment in ERs may be key to ending HIV spread worldwide
In a follow-up study conducted in South Africa, Johns Hopkins Medicine researchers say they have evidence that hospital emergency departments (EDs) worldwide may be key strategic settings for curbing the spread of HIV infections in hard-to-reach populations if the EDs jump-start treatment and case management as well as diagnosis of the disease.

NIH HIV experts prioritize research to achieve sustained ART-free HIV remission
Achieving sustained remission of HIV without life-long antiretroviral therapy (ART) is a top HIV research priority, according to a new commentary in JAMA by experts at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

The Lancet HIV: PrEP implementation is associated with a rapid decline in new HIV infections
Study from Australia is the first to evaluate a population-level roll-out of pre-exposure prophylaxis (PrEP) in men who have sex with men.

Researchers date 'hibernating' HIV strains, advancing BC's leadership in HIV cure research
Researchers have developed a novel way for dating 'hibernating' HIV strains, in an advancement for HIV cure research.

Read More: HIV News and HIV Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to