Progress of HIV research highlights in November 2019

November 27, 2019 / bioun / - -- human immunodeficiency virus (HIV), or AIDS (acquired immunodeficiency syndrome) virus, is a virus that causes human immune system defects In 1983, HIV was first discovered in the United States It is a lentivirus that infects cells of the human immune system It is a retrovirus HIV destroys the T lymphocyte of human body, and then blocks the process of cellular immunity and humoral immunity, leading to the paralysis of the immune system, which leads to the spread of various diseases in human body, and ultimately leads to AIDS Due to the rapid variation of HIV, it is difficult to produce specific vaccine, so far there is no effective treatment, which poses a great threat to human health Since the 1980s, the AIDS epidemic has claimed more than 34 million lives According to the statistics of the World Health Organization (who), it is estimated that 36.9 million people around the world were infected with HIV in 2017, of which only 59% of those infected with HIV received antiretroviral therapy (Art) So far, HIV is still one of the biggest public health challenges in the world, so it is urgent to study the function of HIV in depth to help researchers develop new therapies that can effectively combat the disease In order to prevent the massive replication of virus from damaging the immune system, people with HIV need to take art every day or even for life Although it has been proved that art can effectively inhibit the onset of AIDS, but such drugs are expensive, time-consuming and labor-consuming and have serious side effects There is an urgent need to find a cure for HIV infection What are the major HIV studies or findings in the coming November? Bio Valley editor combed the news about HIV research reported by Bio Valley this month for you to read 1 Science: inducing too many Th1 cells to produce will destroy the efficacy of HIV vaccine doi: 10.1126/scitranslmed.aav1800 if HIV vaccine causes the wrong immune response, the vaccination may be counterproductive Now, in a new study, researchers from the University of Emory and other research institutions in the United States have collected evidence from several non-human primate studies using SIV viruses closely related to HIV virus that building too many soft targets can weaken vaccination aimed at providing protection against virus infection HIV targets and replicates helper T cells (Th cells) that help the body produce an antiviral immune response They found it was crucial that vaccines against HIV did not create more safe havens for the virus The relevant research results were published in the Journal of Science Translational Medicine on November 20, 2019, with the title of "strong Th1 biased CD4 T cell responses are associated with determined SIV vaccine efficiency" The picture is from cc0 public domain Problems arise when vaccination produces too many specific types of type I helper T cells (Th1 cells) These cells migrate to mucosal tissues, such as the rectum, cervix and vagina In most infections, HIV / SIV first enters the body from mucosal tissue These Th1 cells are like the first responders to zombie attacks They initially fight HIV, but then they are taken over by the virus What people need is TFH cells, which stay in the lymph nodes and help the immune system produce antibodies against the virus, said Dr Rama Rao Amara, co-author of the paper and a researcher at the Yerkes National Primate Research Center at Emory University "We're not saying that Th1 cells are bad," he said However, if you have too many Th1 cells, they will make the vaccine unable to produce effective protection " 2 Science: clinical trials show that antigen competition will destroy the efficacy of HIV vaccines doi: 10.1126/scitranslmed.aaw1673 many HIV vaccines are designed to produce strong T-cell responses T cell responses are associated with a reduced risk of HIV infection in uninfected people and control of virus replication in HIV infected people HIV antigen gag specific T cells are mainly related to post infection control, and HIV antigen env antigen is the target of protective antibody Therefore, HIV vaccine design usually contains these two antigens However, the inclusion of multiple antigens may lead to antigen competition, thus reducing the potential efficacy of the vaccine In a new clinical study, researchers from the United States, Brazil, Peru and Switzerland vaccinated participants only with HIV antigen gag / pol, or with HIV antigen gag / pol and env at the same time, to see if antigen competition interferes with CD4 T cell response They found that when both gag / pol and env were inoculated at the same time, the detected CD4 T cell response to gag / pol was lower, indicating that the inclusion of multiple antigens in the vaccine may prevent the largest T cell response Relevant research results were published in the Journal of Science Translational Medicine on November 20, 2019 The title of the paper is "anti competition in CD4 + T cell responses in a randomized, multicenter, double blind clinical HIV vaccine trial" Specifically, this clinical study, called HVTN 084, is a randomized, multicenter, double-blind, phase 1 clinical trial designed to investigate whether the addition of Env to a gag / pol vaccine reduces the magnitude or breadth of the gag / pol specific T-cell response Fifty volunteers received intramuscular injection of 1 × 1010 units (PU) of Rad5 gag / pol and enva / B / C (mixed in a ratio of 3:1:1:1) or 5 × 109 units of Rad5 gag / pol The CD4 + T cell responses measured by cytokine expression at 4 weeks after vaccination were significantly higher in the non env vaccinated group than in the env vaccinated group, but there was no significant difference in the CD8 + T cell responses between the two vaccinated groups They further revealed that compared with the co immunization of gag / pol and env, in the absence of Env, the response of gag / pol specific T cells was more extensive The addition of Env antigen to gag / pol vaccine resulted in a decrease in the response rate and amplitude of CD4 + T cells against gag / pol, as well as a decrease in the width of antigen epitopes, which confirmed the existence of antigen competition 3 Science: heavy weight! Breakthrough HIV vaccine design strategy is emerging doi: 10.1126/science.aax4380 in a new study, researchers from Scripps Institute and other research institutions in the United States successfully verified the principle of an advanced HIV vaccine strategy, which may also effectively protect people from other deadly infectious diseases The related research results were recently published in the Journal of science, and the title of the paper was "a generalized HIV vaccine design strategy for pricing of broad neutralizing antibody responses" Scientists at the Scripps Institute are part of a team that designed and tested a new vaccine candidate (green and blue) that combines with a precursor (tan) of a broad neutralizing antibody to HIV and is expected to be the first phase of a multi-stage HIV vaccine The picture is from schief lab The new vaccine strategy focuses on stimulating the immune system to produce broad neutralizing antibodies (bNAb) against HIV These special antibodies can bind to the important but inaccessible regions on the surface of HIV, and the differences between these regions are not significant among different HIV strains, so they can neutralize many different rapidly mutated HIV strains Vaccines that produce such antibodies can save millions of lives and billions of dollars, and may ultimately help eliminate the major public health problem of AIDS Based on a concept called germline targeting, the new strategy could block millions of different virus strains spreading around the world So far, it has been difficult to achieve this goal No candidate HIV vaccine has been found to induce protective bNAb responses in humans Schief and colleagues have previously demonstrated a reproductive targeting strategy in a particular case: bNAb captures HIV in an unusual way This new method is more powerful because it is suitable for antibodies that capture targets through a more common mechanism In addition, the analysis conducted in this study suggests that this method may also be suitable for the preparation of vaccines against many other refractory pathogens, such as influenza virus, dengue virus, Zika virus, hepatitis C virus and Plasmodium To confirm the feasibility of this strategy, Dr Jon Steichen, a senior scientist at schief laboratory and co-author of the paper, first selected an HIV bNAb known as bg18 as the test case By studying the structure of bg18 when combined with a target on HIV, the researchers identified key characteristics of the antibody's HIV capture capability Next, they searched a huge database of human antibody genes to find B cells that produced antibodies that naturally share the key characteristics of bg18 They then used a complex strategy to select and evolve a set of virus mimic proteins that may potentially activate a variety of bg18 like B cells These proteins will eventually act as "immunogens" to stimulate bg18 like B cells in vaccinated humans Tests on blood samples from HIV negative human donors confirmed that the immunogens designed by the researchers were well combined with B cells with the required bg18 like characteristics of normal circulation 4 Cell Rep: new findings in the field of malaria contribute to the treatment of HIV doi: 10.1016/j.celrep.2019.10.087 according to a recent study, researchers from Australia have found that the immune system's response to malaria infection may contribute to the development of new treatments for hepatitis C, HIV and wolf sore Using laboratory models, researchers found that intense inflammatory signals from malaria infection activate specific molecules that trigger the production of highly effective antibodies against disease The results were published in cell reports Dr Hansen and her team have been exploring how the host immune system responds to malaria infection for the past decade "In our previous paper, we demonstrated that inflammatory signals activate molecules that block the development of helper T cells, which means that B cells do not have the necessary instructions to make antibodies When we start this study, we expect to see that inflammation also has a negative effect on B cells In fact, we find the opposite The inflammatory signal is transmitted to B cells to improve the quality of the antibody Dr Hansen said she hoped the findings would play a role beyond malaria "I think this discovery provides an opportunity to treat chronic viral infections and autoimmune diseases," she said We have identified molecular 'switches' that drive the immune system to produce powerful antibodies, as well as inflammatory signals that affect its function For this molecule or other molecules in the same pathway, it can provide precise means to treat these diseases In chronic infections, including malaria and viral infections, such as HIV and chronic hepatitis C, the production of very high-quality and effective antibodies is essential to eliminate infection On the other hand, B cells that can produce antibodies against autoantigens (proteins and tissues of human body) are the root cause of autoimmune diseases, such as lupus 5 Menopause: women with HIV have an increased risk of premature menopause doi: 10.1097/gme.0000000000001423 HIV positive women now have a longer life expectancy due to advances in medicine, but it makes her