HIV vaccine elicits antibodies in animals that neutralize dozens of HIV strains

June 4, 2018, NIH/National Institute of Allergy and Infectious Diseases
This protein structure diagram illustrates the location of the fusion peptide epitope (red) on the HIV spike (green), which projects out of the viral membrane (grey). The diagram also shows how a broadly neutralizing antibody (yellow) binds to the fusion peptide. Credit: NIAID

An experimental vaccine regimen based on the structure of a vulnerable site on HIV elicited antibodies in mice, guinea pigs and monkeys that neutralize dozens of HIV strains from around the world. The findings were reported today in the journal Nature Medicine by researchers at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and their colleagues.

Peter D. Kwong, Ph.D., and John R. Mascola, M.D., led the study. Dr. Kwong is chief of the Structural Biology Section at the NIAID Vaccine Research Center, and Dr. Mascola is the center director.

"NIH scientists have used their detailed knowledge of the structure of HIV to find an unusual site of vulnerability on the virus and design a novel and potentially powerful vaccine," said NIAID Director Anthony S. Fauci, M.D. "This elegant study is a potentially important step forward in the ongoing quest to develop a safe and effective HIV vaccine."

A preliminary human trial of the new vaccine regimen is anticipated to begin in the second half of 2019.

Today's report reflects one of two broad, complementary approaches NIAID is pursuing to develop an HIV vaccine. In one approach, scientists first identify powerful HIV that can neutralize many strains of the virus, and then try to elicit those antibodies with a vaccine based on the structure of the HIV surface protein where the antibodies bind. In other words, scientists start with the most promising part of the immune response and work to develop a vaccine that will induce it. This method was used to design the vaccine described today.

The other, empiric approach to HIV vaccine development begins by evaluating the most encouraging vaccine candidates for efficacy in people through clinical trials. Then scientists try to build on successful trial results by, for example, examining blood and other clinical specimens from study participants who received the vaccine to identify the most promising parts of the immune response. Researchers subsequently use this information to improve vaccination approaches for future trials. This method was used to develop the HIV vaccine regimen tested in the RV144 clinical trial and the HIV vaccine regimens currently under study in the HVTN 702 and Imbokodo clinical trials.

Over the past several years, HIV researchers have discovered many powerful, naturally occurring antibodies that can prevent multiple HIV strains from infecting human cells in the laboratory. About half of people living with HIV make these so-called "broadly neutralizing" antibodies, but usually only after several years of infection—long after the virus has established a foothold in the body. Scientists have identified and characterized the sites, or epitopes, on HIV where each known broadly neutralizing antibody binds. Many laboratories around the world are developing HIV vaccine candidates based on the structure of these epitopes with the goal of coaxing the immune systems of HIV-negative people to make protective antibodies after vaccination.

The experimental vaccine described in today's report is based on an epitope called the HIV fusion peptide, identified by NIAID scientists in 2016. The fusion peptide, a short string of amino acids, is part of the spike on the surface of HIV that the virus uses to enter human cells. According to the scientists, the fusion peptide epitope is particularly promising for use as a vaccine because its structure is the same across most strains of HIV, and because the immune system clearly "sees" it and makes a strong immune response to it. The fusion peptide lacks sugars that obscure the immune system's view of other HIV epitopes.

To make the vaccine, the researchers engineered many different immunogens—proteins designed to activate an immune response. These were designed using the known structure of the fusion peptide. The scientists first assessed the immunogens using a collection of antibodies that target the fusion peptide epitope, and then tested in mice which immunogens most effectively elicited HIV-neutralizing antibodies to the fusion peptide. The best immunogen consisted of eight amino acids of the fusion peptide bonded to a carrier that evoked a strong . To improve their results, the scientists paired this immunogen with a replica of the HIV spike.

The researchers then tested different combinations of injections of the protein plus HIV spike in mice and analyzed the antibodies that the vaccine regimens generated. The antibodies attached to the HIV fusion peptide and neutralized up to 31 percent of viruses from a globally representative panel of 208 HIV strains.

Based on their analyses, the scientists adjusted the vaccine regimen and tested it in guinea pigs and monkeys. These tests also yielded antibodies that neutralized a substantial fraction of HIV strains, providing initial evidence that the vaccine regimen may work in multiple species.

The scientists are now working to improve the vaccine regimen, including making it more potent and able to achieve more consistent outcomes with fewer injections. The researchers also are isolating additional generated by the vaccine in monkeys, and they will assess these antibodies for their ability to protect the animals from a monkey version of HIV. The NIAID scientists will use their findings to optimize the and then manufacture a version of it suitable for safety testing in human volunteers in a carefully designed and monitored clinical trial.

Explore further: Study discovers new HIV vaccine target

More information: Kai Xu et al, Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1, Nature Medicine (2018). DOI: 10.1038/s41591-018-0042-6

Related Stories

Study discovers new HIV vaccine target

May 12, 2016
A team led by scientists at the National Institutes of Health (NIH) has reported a research trifecta. They discovered a new vulnerable site on HIV for a vaccine to target, a broadly neutralizing antibody that binds to that ...

Study suggests potential hurdle to universal flu vaccine development may be overcome

August 15, 2012
In the quest for a universal influenza vaccine—one that elicits broadly neutralizing antibodies that can protect against most or all strains of flu virus—scientists have faced a sobering question: Does pre-existing ...

Antibodies help protect monkeys from HIV-like virus, scientists show

May 5, 2011
Using a monkey model of AIDS, scientists have identified a vaccine-generated immune-system response that correlates with protection against infection by the monkey version of HIV, called simian immunodeficiency virus (SIV). ...

Modified experimental vaccine protects monkeys from deadly malaria

May 22, 2017
Researchers from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, modified an experimental malaria vaccine and showed that it completely protected four of eight ...

Vaccine strategy induces antibodies that can target multiple influenza viruses

July 22, 2016
Scientists have identified three types of vaccine-induced antibodies that can neutralize diverse strains of influenza virus that infect humans. The discovery will help guide development of a universal influenza vaccine, according ...

Researchers find alternative pathways to HIV antibodies

May 4, 2016
The immune system appears to hamper an investigational vaccine from inducing antibodies that protect against HIV infection, but there may be ways to overcome this impediment, according to research led by the Duke Human Vaccine ...

Recommended for you

New simulation tool predicts how well HIV-prophylaxis will work

June 14, 2018
A new mathematical simulation approach predicts the efficacy of pre- and post-exposure prophylaxis (PrEP) medications, which help prevent HIV infection. The framework, presented in PLOS Computational Biology by Sulav Duwal ...

Many at risk for HIV despite lifesaving pill

June 11, 2018
Multiple barriers may stop high-risk individuals from accessing an HIV drug that can reduce the subsequent risk of infection, according to a new University of Michigan study.

Active HIV in large white blood cells may drive cognitive impairment in infected mice

June 7, 2018
Macrophages, large white blood cells that engulf and destroy potential pathogens, harbor active viral reserves that appear to play a key role in impaired learning and memory in mice infected with a rodent version of HIV. ...

HIV vaccine elicits antibodies in animals that neutralize dozens of HIV strains

June 4, 2018
An experimental vaccine regimen based on the structure of a vulnerable site on HIV elicited antibodies in mice, guinea pigs and monkeys that neutralize dozens of HIV strains from around the world. The findings were reported ...

HIV study reveals new group of men at risk of infection

June 4, 2018
A group of men who may be underestimating their HIV risk has been identified in a new study.

Discovery reveals how cells try to control levels of key HIV protein

May 31, 2018
One of the many challenges in treating HIV is that the virus can lie dormant in cells, quietly evading immune detection until it suddenly roars to life without warning and begins replicating furiously. Salk Institute researchers ...

2 comments

Adjust slider to filter visible comments by rank

Display comments: newest first

Anonym330907
not rated yet Jun 05, 2018

I started using multiple sclerosis (MS) herbal remedy i purchased from Best Health Herbal Centre January this year. I only used it for a month and two weeks, my condition changed automatically, all my symptoms are gone. Remaining positive have helped me during this treatment. Now am living MS FREE.
Hope this will help somebody, remember, do your own research and make your own decisions based on information you have received and digested. Thanks to Best Health Herbal Centre for their amazing work. Forever Grateful!
Contact them via w ww .besthealthherbalcentre. com
sayemahmooda_gma
not rated yet Jun 05, 2018
My name is Mahmooda Sayed, I am from Texas,USA. I am sure this information will be useful to the general public on how my sister was cured from Genetic Herpes with the same herbal practitioner who also got me cured from HIV/AIDS,The medication was administered by Dr Zulu. He cures other diseases too. For further information visit Drmohamendherbalremedy@gmail.com, For those of us that would come back appreciating me or might need further information, the above name is my Facebook name or you can also write me mails at sayemahmooda@gmail.com

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.