HIV treatments currently need to be taken regularly for life – long-lasting antibody treatments could one day provide an equally effective alternative to a single dose

antiviral treatment It has had a tremendous impact on the treatment of HIV infection worldwide. The Millions of people Currently, taking these remedies under medical supervision reasonably can reduce their viral loads to undetectable levelsEliminate the risks of transmission and live a normal life. However, antiretroviral therapy is not without shortcomings. People need to take these medications regularly for life, and Low compliance It can lead to drug resistance.

There is a promising new option on the horizon. I A researcher who studies AIDS treatmentsAnd I believe in that monoclonal antibodies They can become game-changing agents in the treatment of HIV infection.

HIV poses a challenge to the immune system.

HIV presents challenges for antibodies

Antibodies They are proteins that play a key role in the immune system’s response to disease-causing pathogens, and allergens that cause allergic reactions. Antibodies recognize specific markers, or antigens, of a potentially harmful substance and help the body get rid of it.

Over the past few decades, researchers have been able to isolate individual antibodies specific to the individual pathogens or allergens they are supposed to attack. With this progress, monoclonal antibodies Made in the lab A major sector of the pharmaceutical industry. You can see many advertisements on TV or in magazines promoting monoclonal antibodies to treat osteoporosis, autoimmune disorders, and various types of cancers.

Antibodies can also be used to treat viral infections, including COVID-19. But the use of antibodies becomes more complicated with HIV, the virus that causes AIDS in humans.

One of the reasons is that he has HIV Huge number of variables It spreads all over the world and even within an infected individual. In fact, the genetic variance of HIV within a single patient exceeds the genetic variance of all influenza strains circulating worldwide during the entire influenza season.

The immune system of an individual infected with HIV produces antibodies to neutralize the virus. However, because these antibodies usually only recognize a specific strain, they are unable to neutralize other HIV strains circulating in the population. Moreover, HIV can Mutation in an infected individual and escape from the antibodies of the original infection-causing variant.

This ability to mutate and escape persistent immune responses is a critical factor in the virus’s ability to continuously replicate, a hallmark of AIDS. It also makes it difficult to design an antibody treatment that can explain the huge genetic variation of HIV.

Monoclonal antibodies are used to treat many types of cancer.

Large-scale neutralizing antibodies show promising results

The discovery of rare individuals who make antibodies to HIV that could be effective against them Up to 80% of circulating strainsHowever, it has boosted the possibilities of antibody therapy for HIV.

these Broadly neutralizing antibodiesor bnAbs, impressive results. Monkey studies They discovered that giving a single dose of bnAbs can prevent infection from human immunodeficiency virus (SHIV), a non-human primate version of HIV. One study found that Two broadly neutralizing antibodies It was able to reduce viral loads to undetectable levels in infected monkeys.

In people, one study runs Two bnAbs He also experienced suppression of HIV replication and nearly undetectable viral loads. One early clinical trial showed in 2021 that one bnAb can provide protection against HIV infection.

Long-term antibody production

All of the studies in monkeys and humans mentioned above required broad re-administration of neutralizing antibodies every three weeks or so to maintain effective concentrations. This leads to the same problem as ART in terms of requiring the individual to repeatedly retake the drug for life. But researchers have found a potential solution.

The use of a small virus that does not cause disease, called adeno-associated virus, to deliver neutralizing antibodies on a large scale to the body can stimulate muscle cells to produce these antibodies continuously. Because muscle cells have Long life They can last an average of 10 to 16 years, and can be turned into factories that mainly produce antibodies for life.

Broadly neutralizing antibodies can target many strains of HIV circulating around the world.

One study my colleagues and I conducted using an adeno-associated virus found that a single monkey was able to produce these antibodies for it. More than six years after one injection.

Another monkey that researchers have dubbedMiami monkey“It is considered functional cure, which means that its viral loads have been at undetectable levels for extended periods even without continuous antiviral drug therapy. two more monkeys They were also cured of HIV infection with this approach.

HIV-associated vectors in HIV antibody therapies still face another hurdle: Antibodies to the drug, or antibodies produced by the body in response to antibodies in treatment. Antibody to drugs can occur when the body registers an antibody treatment as a foreign body and mounts an immune response against it, invalidating the treatment. They have also caused problems with antibody therapies in cancer And the autoimmune disorders. This may be particularly the case for broadly neutralizing antibodies, which have unusual structures that deviate from what the body would normally expect the shape of an antibody to look like.

Researchers are working hard to develop simple and accessible methods to help patients build tolerance to broadly neutralizing antibodies. Some of these approaches involve introducing treatments to other areas of muscle with greater immune tolerance, such as for the liver And the through the mouth.

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