Successful production of antibodies that experimentally neutralize the HIV virus

An experimental HIV vaccine has produced antibodies that can neutralize a wide variety of strains of HIV. HIV poses a huge challenge to humanity. As we celebrate the 31st edition of World AIDS Day on December 1, the hope of wiping out the disease that killed 770,000 people in 2018 is at its highest.

A team of scientists from Scripps Research (USA) has developed an experimental HIV vaccine. The IAVI, a non-profit association aimed at accelerating the development of an AIDS vaccine, also participated in this research. The results of their tests were published in the journal Immunity.

Number of death due to HIV (WHO 2019)

Crazy game with virus !

The tests have been done on rabbits, and the results are promising. They helped develop widely neutralizing antibodies, called bnAbs, which can target at least two critical sites on the virus. Researchers believe that this vaccine can provide robust protection against this constantly evolving virus.

To get into the cell, HIV has the Env protein, which covers the entire virus. These proteins function as “keys” to enter and infect a cell. Thanks to Env, HIV can attack a particular type of white blood cell, called CD4 lymphocytes. Like Env, CD4 covers the whole lymphocyte and represents the “lock” of white blood cells. When the Env encounters CD4, the virus “key” opens the “lock” of the white blood cell to infect it.

Knowing this approach technique, the researchers tried to fool the white blood cells so that they were ready when they encountered HIV. They then created synthetic liposome (fat-like molecules that cover Env proteins) the size of a virus, which will serve as the basis for the vaccine. When these fake viruses come into contact with lymphocytes, the latter will be able to defend themselves.

Richard Wyatt

“The idea was to better expose this site and thereby stimulate a broad antibody response against it from the start,”

Lead study author and professor in the department of immunology and microbiology at Scripps Research

Promising results

The team administered the vaccine to 12 rabbits and discovered that five of them had developed antibodies that neutralized several HIV isolates. Subsequently, the antibodies were analyzed to determine which rabbits responded strongly to it, and also to identify two distinct types of bnAb. The first, called E70, blocks the CD4 binding site as expected by partially capturing glycans (a component of the cell membrane), which researchers say is unusual.

The second, called 1C2, attacked a different but well-known vulnerability point on Env, which is the interface between two key segments of the complex protein.

The binding of the 1C2 antibody destabilizes Env, which is therefore no longer able to ensure the entry of HIV into host cells. This reaction had an unusual extent of neutralization since it blocked 87% of a panel of 208 distinct HIV isolates.

“This discovery is important evidence that HIV vaccination, if done the right way, can achieve the goal of inducing bnAbs at multiple sites on the virus”

Richard Wyatt.

Perform large-scale, inexpensive treatment

This means that researchers are now a little closer to developing an effective HIV vaccine, which would certainly be a major goal of medical science since 1983, when the virus was first discovered. “This is a first proof of principle, but it is important, and we are now working to optimize this vaccine design,” insists Richard Wyatt.

According to UNAIDS data, more than 38 million other people are currently living with HIV and around 35 million people have died from immunodeficiency syndrome. Existing antiviral drugs only keep people living with HIV alive longer while reducing their ability to transmit the virus to others.

However, they do not clear the infection and must be taken indefinitely. With an effective vaccine, it would be possible to prevent the acquisition of the virus. Such a drug could also eliminate HIV as a major threat to public health if an inexpensive dose is administered to uninfected people.

Until now, targeting HIV has been extremely difficult for vaccine designers, due to its rapid mutation and other mechanisms to avoid immune attacks. Test by Richard Wyatt and his team confirms that vaccination can trigger the types of antibodies needed to provide general protection against HIV, such as bnAbs, which binds to critical sites in the virus that do not vary much one strain to another.

Researchers say that while the vaccine can stimulate the immune system – in most or all people – to produce bnAbs that hit multiple vulnerable sites in the virus, it can offer effective protection against HIV.

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