艾滋病 z-bo 2020-09-18 334

　　Based on the preliminary results of experimental testing of a new generation of broadly neutralizing antibodies in HIV patients, researchers from Rockefeller University confirmed that this experimental therapy can significantly reduce the amount of virus in the patient's blood. The research work published this week in the journal Nature has brought new optimism to the field of HIV immunotherapy and proposed some new strategies to combat or even prevent HIV infection.

　　There is a continuous arms race between the virus and the body's immune system in people infected with HIV. When the body produces some new antibodies to target the virus, the virus is constantly mutating to escape the antibody, always trying to get a few steps ahead. This new study completed by Michel Nussenzweig Molecular Immunology Laboratory found that giving an effective antibody called 3BNC117 can catch HIV off guard and reduce viral load.

　　In the past, testing for HIV in humans always showed disappointing results. 3BNC117 belongs to a new generation of broadly neutralizing antibodies, which can effectively fight against a wide range of HIV virus strains. The paper’s co-first author, Nussenzweig Laboratory Clinical Research Assistant Professor Marina Caskey said: “The special thing about these antibodies is that they are active against more than 80% of HIV strains and are very effective.” 3BN117 was originally tested by Nussenzweig. It was isolated and obtained by Johannes Scheid from the laboratory. It targets the CD4 binding site on the HIV envelope. The CD4 receptor is the main site where HIV attaches to host cells. 3BNC117 shows that 195 of the 237 HIV strains Fight against vitality.

　　Approximately 10-30% of HIV-infected people will naturally produce broadly neutralizing antibodies, but they all appear several years after infection. At that time, the viruses in their bodies have usually evolved to escape these powerful antibodies.

　　By isolating and cloning these antibodies, researchers can use them as therapeutic drugs against HIV infections that take less time to prepare. In previous research work, Nussenzweig's laboratory confirmed that these effective antibodies can prevent or inhibit infection in HIV models in mice and non-human primates. Caskey said, but these animal models are roughly similar to human infections. Mice must be genetically engineered to be susceptible to HIV infection. Therefore, they lack a complete immune system. Primates used in HIV research will only be infected with a monkey version of the virus. Therefore, human trials are needed to obtain proof of principle.

　　In this new study, the researchers administered the antibody to HIV-infected and uninfected individuals in a single intravenous manner, and monitored them for 56 days. The highest dose level tested in the study was 30 milligrams per kilogram of body weight. The amount of virus measured in the blood of all 8 infected individuals who received treatment showed a 300-fold drop, and most of them reached their minimum viral load one week after treatment. The decline in viral load depends on the individual’s initial viral load and the sensitivity of their particular HIV strain to antibodies.

　　This is the first time this new generation of HIV antibodies has been tested in humans. Not only can a single dose of 3BN117 be well tolerated, it can effectively temporarily reduce the viral load, and it can remain active for a long time in some individuals. In half of the individuals who received the highest dose, their viral load was still below the initial level at the end of the 8-week study period, and 3BNC117 resistance did not develop. Researchers believe that these antibodies may also enhance the patient's immune response to HIV, which in turn can better control the infection. In addition, antibodies such as 3BNC117 may also be able to kill viruses hidden in infected cells. These viruses serve as virus reservoirs that current antiretroviral drugs cannot reach.

　　Most likely, like other antiretroviral drugs, 3BNC117 will be used in combination with other antibodies or antiretroviral drugs to control infection. Caskey said: "Just like a single drug, because drug resistance will appear, a single antibody is not enough to suppress the viral load for a long time. An important benefit is the dosing regimen: an HIV antibody treatment only requires a few minutes each. Treated once a month, compared to current first-line HIV treatment requiring daily antiretroviral drugs."

　　"Compared with traditional antiretroviral therapy, antibody-mediated therapy can also involve the patient's immune cells to help better neutralize the virus," the co-first author of the paper, Florian, Nussenzweig Laboratory Assistant Professor of Clinical Research Klein said.

　　In addition to the potential for treatment, the new research also brings hope to HIV vaccines. If researchers can induce the immune system of uninfected individuals to produce effective antibodies such as 3BNC117, it may be enough to block HIV before it establishes infection.

　　In addition, Nussenzweig Laboratory and Rockefeller University Hospital are conducting another clinical study to clarify the effect of other broadly neutralizing antibodies on the viral load of HIV-infected patients when used alone or in combination.