Why is 3BNC117 antibody a new hope for HIV treatment?

A new treatment recently announced by Rockefeller University a few days ago has basically been able to "suppress" the growing and farther HIV virus, possibly hoping to find a vaccine for the disease. this century.

Learn 3BNC117 antibodies to reduce the amount of HIV virus in the blood

HIV (green) virus attacks the white (white) cells of humans

This method is based on a neutral antibody called 3BNC117 . It is unclear whether 3BNC117 is able to "kill " HIV, but it prevents HIV from infecting new white blood cells , especially CD4 cells. It's that simple, but why is it considered so promising?

HIV does not directly kill people!

First of all, we need to learn some basic information about HIV and why it is dangerous.HIV is written by Human Immunodeficiency Virus , also known as human immunodeficiency virus. This virus only attacks the immune system. The same type of simian immunodeficiency virus (HIV) with SIV also causes an impairment of the immune system but only attacks other human primates. Many studies suggest that HIV is a mutation of SIV, in which SIV CPZ (chimpanzee or chimpanzee) is considered a bridge between SIV and HIV.

White blood cells (yellow) are "eating" bacteria (orange)

In fact, HIV itself is not lethal, but its goal is the immune system (immune system). So when the number of white blood cells decreases, it facilitates other pathogens to attack the human body (which was previously not possible when the immune system was strong), leading to depletion of the body. and finally death (AIDS syndrome). This is similar in human society, if the police force always works effectively to suppress crime, society will be very safe. However, if a number of criminals only attack the police, causing the police to weaken, other criminals have "rising" conditions and society will become unstable. HIV is the main danger in that - attacking the only " policing " system of people.

Therefore, HIV infected people do not die immediately after a few months or weeks such as rabies virus, flu, Ebola . usually after 9 - 11 years, when the immune system is exhausted. This number may also change if the infected person's body has been weakened because of other types of epidemics before.

How HIV works

Similar to other viruses, HIV reproduces and infects cells with parasites . When HIV approaches white blood cells (such as macrophages or CD4), the two-protein binding gp120 & gp41 will attempt to bind to the CD4 receptor on the cell membrane. When this bond is created, the CD4 protein will change shape, giving the head gp120 access to another contact, CCR5. When gp120 "unlocked" CCR5, the white blood cell membrane and virus envelope blend together, helping to bring the genetic information of HIV (RNA) into the cell .

Create an HIV

But HIV RNA will not do anything if it is not reverse transcripted into DNA. This process is caused by an RT (Reverse transcriptase) enzyme that is available inside the virus and is " attached" to HIV RNA. This type of enzyme is specific to the retrovirus group with the " style " of reverse transcription of RNA to DNA, which HIV is one of them. RT Enzyme is "beneficial " in that it turns a single RNA sequence into a double DNA sequence, making the " fake " process more complete than ever.

The glycoproteins of HIV are invading white blood cells through CD4 & CCR5 ports

After the "spy " DNA was created, it could now enter the cell nucleus and "hide" into a part of cell DNA. This process is once again "assisted" by the IN enzyme (Integrase) that is also available in HIV. The enzyme will "cut" the DNA of the stem cell and " insert " the "spy" DNA in the middle, then "paste " to make everything "look new".

An overview of the life cycle of HIV from infiltration until reconstruction

Basically, to this step, the main purpose of HIV is complete. From here, everything happens automatically when white blood cells "live and work " like other cells. It will translate the DNA in the cell nucleus (infected) to synthesize the necessary proteins that are the raw material for the new virus. It will also transcribe (transcript) to turn DNA into new RNA. This RNA will then combine with the new materials and the newly born virus, following the "career " of infection and infection.

The mischief of HIV

HIV infection is not only known to scientists. In fact, it is the human immune system that "knows" them first. The change of macrophage cells as well as the disappearance of CD4 cells are all perceived by the human body. Of course, the immune system will find ways to deal with this pathogen . But why did they fail?

"Relatives " of HIV, SIV, which only infect other primates, are also infected in the same form. SIV is believed to have existed at least 32,000 years ago . With such a long lifetime and with the " kissing" life of many monkeys, gibbons . they should have all been extinguished. On the contrary, all of them are still alive and well with "flood ". Studies show that although the bodies of the above primates have relatively high levels of SIV, they do not turn to AIDS as in humans . Why?

Genetic relationship diagram between SIV and HIV

There are 2 reasons. One is that the immune systems of these species have "learned" how to survive with SIV, so they do not harm the host. Secondly, SIVs do not have "toxicity" like HIV - more precisely, SIVs do not have high mutation rates and short life cycles like HIV. On average, about 10 billion new HIV viruses are born each day, with a high rate of mutation - 3 times every 10,000 copies of nucleotide radicals (A, T, C, G) are changed. . With that characteristic, from an initial line of HIV, there will later be hundreds of HIV strains with different traits. To the extent that people have to divide HIV into groups (groups) and even within the M group (accounting for 90% of cases of HIV infection), there are dozens of other subtypes.

HIV groups and subgroups have been recorded

It is this diversity of HIV strains that not only makes scientists " confused " in treating them but also the human immune system fails before this "ghost" virus. The practice of HIV mentioned above is in fact just one of many ways of infection. HIV variants later "find " other protein sites on the cell membrane to penetrate. Even when HIV has grown, in the same infected cell there may be many HIV strains with different "intrusion" ways.

In addition, we should note that HIV currently has two main types - HIV-1 & HIV-2 . In which HIV-1 is the type that people often mention. While HIV-2 is genetically, it is closer to SIVmm than to HIV-1. HIV-2 is actually farther away from HIV-1 than SIV CPZ (considered a bridge between SIV and HIV). HIV-2 eventually caused AIDS, but the time to occur was much longer than that of HIV-1 and it was relatively " benign " than the other brother. Because of lower infectivity than HIV-1, HIV-2 is mainly concentrated in some West African countries but not as widespread as HIV-1.

And new hope .

From the above sections, we can see that HIV (or HIV-1) is dangerous and difficult to treat in that they have a very rapid mutation rate . This mutation ability helps them to develop resistance after a period of treatment (those that are affected will slow down, but new lines of resistance continue to grow rapidly). This is why, so far, people have not found a cure for HIV-1 completely.

But as mentioned, the confrontation between HIV and the immune system is not just a game of HIV itself. The immune system itself also seeks to identify new HIV strains and destroy them. The only problem is that the immune system is often " one step behind" before HIV and eventually the body turns to AIDS.

The possibility of mutation of HIV thanks to transciptase enzyme with the ability . high "error" translation

But this arms race may have another outcome .

Try to look back at the history of humanity through the Second World War (WW2). We all know that the Germans have failed after being depleted in resources and have no more resources to confront the Soviets (Russia) on the east side as well as the British American forces on the west. But by the end of the war, the Germans had also invented important weapons that most powerful powers would later use such as jets, stealth aircraft, ballistic missiles, engine submarines. electricity . At the time the Germans made them, Allied nations had no weapons that were really effective against them. Allies won because the Germans were exhausted to mass produce.

So what if the Germans made all these things from the beginning of WW2 instead of the end of the war? It is very possible that the world today is very different .

The story of the immune system and HIV is similar.The 3BNC117 antibody mentioned at the beginning of the article is the "research" result of the human immune system itself . On average, 10-30% of patients have developed this antibody after a period of HIV infection. Unfortunately, when the patients' bodies extracted 3BNC117, their HIV lines "took a step forward" .

But what if 3BNC117 is present in the body from the day when it was infected?

According to a Rockefeller University study, 3BNC117 is very effective when preventing HIV from reaching the CD4 position on the white blood cell. If the virus does not penetrate the host cell, it will not regenerate and the purpose of infection fails. Researcher Marina Caskey of 3BNC117 said: "The special thing about this type of antibody is that they are effective at up to 80% of HIV strains and they are very potential (to make drugs)" .

3BNC117 prevents HIV from reaching the CD4 portals present on cell membranes

The Rockefeller University study found that 3BNC117 "stopped" the spread of 195 out of a total of 237 known HIV strains . In a series of human trials, at the highest dose (30 mg of 3BNC117 / 1 kg of patients), all patients showed a 300-fold decrease in the amount of virus in the blood! Most patients achieve the lowest viral level after only 1 week of injection. This rate of decline depends on the amount of virus present and the number of strains affected by the time before injection.

Besides, 3BNC117 not only has an immediate "acute" impact but also a "chronic " long term . In some patients, even with a single injection, the effects of 3BNC117 continue to last. Of the half of the highest-dose patients, the amount of virus in the blood was kept lower than before the injection for 8 weeks (when the trial ended) and no 3BNC117 resistance was seen. It is possible that the earlier the injection time before HIV mutation is, the higher the effect.

In addition, this study predicts the 3BNC117 HIV detection capacity. Accordingly, 3BNC117 can penetrate previously infected cells, which act as "barracks " to train HIV and destroy them. This ability to penetrate is not possible for current antiretroviral drugs. However, 3BNC117 with " superhuman" ability will need to be studied in more detail. If yes, this is really good news for all HIV research institutions.

Of course, we should not rush to celebrate this information. In fact, the patients who were able to make 3BNC117 themselves eventually died, because still 20% of HIV "escaped" . However, hope that their departure is not useless for the rest of the human race. As soon as HIV is detected, the number of them in the body is not high and of course, the number of mutants will not be much . In the case of HIV that has not yet mutated into the "escape" lines 3BNC117, it is still possible to treat (but the patients already have mutations, we still have to condolence with them).

Replace the ending .

3BNC117 or any other antiretroviral drug, of course, is not enough to " suppress" if only one type is used. They need to be combined to be able to treat many different strains of viruses. "Only one type of antibody, like just one drug, will not be able to suppress all viruses because after all, resistance will appear," Caskey said .

Hopefully soon there will be a day when people can fully treat HIV / AIDS

Meanwhile, co-author, Florian Klein, is optimistic about 3BNC117: "In contrast to traditional retrovirus therapy, antibody-based therapy that allows active access to infected cells, will give more effective removal of viruses from the body ".

Rockefeller University researchers also expected to find a vaccine for HIV from 3BNC117 . Because in addition to healing use, 3BNC117 can play a role in preventing disease. They hope that if they can help the bodies of non-HIV-infected people to self-create 3BNC117 from the beginning, they will be able to "lock down" HIV before the virus can germinate in the body.

However, from now until the dream comes true, always carry a condom and avoid sharing needles. Because in the end, the room is better than curing.