A new HIV vaccination strategy successfully tested for mice



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The search for a HIV vaccine was in the hands of scientists for many years, and despite some advances in the field, most of the failures were in researchers of journals. A new vaccination method based on the structural modification of the viral protein About Has successfully tried in mice and could present one of the first real advances in the fight against HIV over the past 30 years.

The new vaccination strategy, described in an article published in the journals Science Advances, Is based on the HIV envelope protein, called About. This complex molecule, with its variable form, was very difficult to synthesize in vaccine, so as to affect an effective immune system against HIV.

However, scientists from Scripps Research Have found a simple and smart way to stabilize proteins About In the desired form, including various strains of HIV.

Mounted on particles resembling viruses, to mimic a real virus, proteins About Stabilized antibodies have proven healthy anti-HIV antibodies in mice and rabbits. Candidate vaccine based on this strategy is now tested in monkeys.

" We hear the new approach as a general solution to the long-standing challenges of designing a HIV vaccine Says Jiang Zhu, Associate Professor in the Department of Structural Biology and Integrative Informatics Scripps Research.

Target viral surface protein About

SinceAbout Plays a crucial role in infection and is the most exposed viral structure of an immune system infected hosted, it is the main purpose of HIV vaccination efforts. The idea was to accumulate people with protein About Full or subunits thereof in order to stimulate the production of antibodies binding AboutIn the hope that they will prevent HIV from infecting host cells in future exposures to the virus.

hiv virus structure

Viral envelope protein About (GP 120 and GP41) is crucial in the infection of the host cell. It allows you to pair and initiate its insertion into the cell, so it is a direct target for a vaccine. Credits: Patrice Boucher

Many researchers believe that a vaccine can work if it has the proteins About To the immune system in a way that looks a lot like the shape of theAbout On a real virus before it infects a cell. But correctly present this protein is a huge challenge.

On the same topic: first promising results for human clinical trials of a HIV vaccine

On HIV, About Is present on the tightly clustered viral membrane of three structures, called trimmers, and the complex structures adopt radically different forms before and after infection of cells. Researchers, despite years and tens of millions of dollars of experiments, have never managed to find an effective way to stabilize the trimmers ofAbout In the preferred form before infection.

" The trimmer stabilization solutions that have been reported so far have worked for some heavy strains, but can not be generalized Zhu explains. " The Metastability of Env has indeed been a major issue for the design of a Hemer-based HIV vaccine ".

A strategy based on the structural modification ofAbout

Zhou, a trained biophysicist, sought a more general solution to resolve the problem of stability. In an article published in 2016, his colleagues from Scripps Research And he suggested that the modification of a short and linear section ofEnv, Called hr 1, can do the trick.

In the new study, researchers have shown that this strategy is proving effective for trimmersAbout From various strains of HIV circulating in different parts of the world. The so-called "Optimized Non-Cleaved Prefusion" (UFO) approach makes it possible to get trimmers ofAbout Stabilized in the closed form, and can be efficiently produced with a surprisingly reduced need for cleaning, in the types of cells normally used in biotechnological manufacturing.

Trimming Protein Approx

This painting shows, on the left, a modified transmitter trimer (in yellow) bound by neutralizing antibodies. On the right, some modified trimmers (in yellow) included in a nanoparticle (blue) to copy a whole virus. Credits: Jiang Zhou / Scripts Research

Zhu and colleagues have yet to optimize their vaccination strategy by genetically linking their trimmersAbout Stabilized, up to 60 at a time, to individual nanoparticles mimic the globular form of a whole virus. In this way, the vaccine molecule, though artificial and disposed of the genetic material necessary for viral replication, appears to the immune system as a true invasive virus and stimulates a stronger reaction.

In just eight weeks in the mouse, Xu and his team discovered that a vaccine sample AboutIn non-antipodes, the appearance of antibodies that, in laboratory tests, has neutralized a commonly circulating strain of HIV – from a type against which former candidate vaccine has generally failed.

" This is the first time that a HIV vaccine candidate induces the type of antibody response in mice Zhou says. Similarly, unprecedented results have been found in rabbits, demonstrating that the nanoparticle-based approach is clearly higher in the use of proteins. About isolated; It induces a much stronger response, and much more quickly.

Other tests are currently under 21 monkeys Southwest National Primate Center, Under the authority of National Institutes of Health.

" We are currently testing two vaccine candidates based on strains of different strains, as well as a third-party vaccine consisting of a cocktail of three en-based vaccines. We believe that the new method represents a breakthrough after 30 years of research on a HIV vaccine Explains Ji Lee, director of UFOAX LLC, the biotechnology laboratory currently testing.

Sources: science advances
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