HIV vaccine

Creative BioLabs is a contract research organization based in New York that specializes in antibody discovery and engineering. They also provide biomanufacturing solutions. The transcript discusses HIV, its structure, life cycle, and challenges in developing a vaccine. HIV is a virus that causes acquired immunodeficiency syndrome (AIDS) and is transmitted through blood, body fluids, and from mother to child. The virus attaches to CD4 positive T cells and enters the cell through a fusion process. HIV can remain latent in the body for years before replication occurs. The transcript mentions different types of HIV vaccines, including live attenuated, protein subunit, live recombinant, and DNA vaccines. Developing an HIV vaccine is challenging due to the lack of natural immunity, frequent mutations of the virus, and the difficulty in determining the immune response needed for protection. Welcome to Creative BioLabs, 100% of the effort, 100% of the service. As a dynamic contract research organization, we are based in New York and serve the whole world. Our seasoned scientists are skilled in antibody discovery, antibody engineering, and biomanufacturing solutions. Hi everyone, this is Joyce from Creative BioLabs Vaccine. Today, I will introduce some knowledge about HIV vaccine. I hope what I provide can help you with your research. All my introduction includes the introduction of HIV, structure of HIV, life cycle of HIV, the pathogenesis of HIV infection, the development of HIV vaccine, challenges of HIV vaccine, and what we can provide with you. HIV is an abbreviation for human immunodeficiency virus, a lentivirus that causes acquired immunodeficiency syndrome, which is a disease that gradually damages the body's immune system, and patients eventually die from various pathogen infections and cancer. In the absence of treatment, HIV infected patients typically have a survival time of 9 to 11 years. HIV is a sexually transmitted virus that can be transmitted through contact with or transfer of the blood or body fluids, such as semen of infected people. In addition, the virus can also be transmitted from infected mothers to newborns during childbirth or lactation. The human immunodeficiency virus is about 120 nanometers in diameter and roughly spherical in shape. The lipid membrane is a fat bilayer that is recruited from the cell membrane of the cell a new virion buds from, and it accounts for about 30% of the total weight of the virion and contains all of the virions except the glycoprotein spikes named GP160. Each GP160 spike splits to form two glycoproteins, the docking protein GP120 on the outside of the virion's membrane, and the transmembrane protein GP41 that actually pierces the viral membrane. GP160 is the part of an HIV virion that attaches it to a target cell, most often a CD4 positive T cell. Each of GP120 and GP41 is a trimer. When a virion attaches to a target CD4 positive T cell, the tumors open to create a mechanism that, along with the cell's CD4 receptor and either of the two co-receptors CCR5 or CXCR4, accomplishes entry into the cell. Inward, there is a spherical matrix formed by protein P17 and a semi-conical capsid formed by protein P24. The capsid shows a high electron density under electron microscope. The capsid contains the viral RNA genome, reverse transcriptase, integrase, protease, and other components from host cells, such as Trenolase 3, the primers for reverse transcription. HIV uses the machinery of the CD4 cells to multiply and spread throughout the body. This process, which is carried out in seven steps or stages, is called the HIV life cycle. The seven stages of the HIV life cycle are binding, fusion, reverse transcription, integration, replication, assembly, and budding. When HIV enters the target cell, its genome is reverse transcribed into double-stranded DNA, which is then transported to the nucleus and integrated into the host DNA. The integration of the viral genome with the DNA of the host cell allows the virus to be latent, preventing virus and its host cells from being detected by body's immune system. HIV could be resting in the human body for 10 years at most after the primary infection, during which the carriers do not show any symptoms. There is also the possibility that the integrated DNA is transcribed, so new viral genomes and proteins are produced, leading to the formation of new viral particles and their releases from the host cells, which ultimately initiate the viral replication cycle. HIV selectively invades CD4 molecules, including T4 lymphocytes, monocytes, macrophages, dendritic cells, and so on. The CD4 molecules on the surface of cells are HIV receptors. After the binding of HIV envelope protein GP120 to CD4 on the cell membrane, GP120 configuration changes expose GP41. At the same time, GP120-CD4 binds to the chemokine CXCR4, or CXCR5, on the surface of target cells to form CD4-GP120-CXCR4-CXCR5 trimolecular complexes. GP41 plays the role of a bridge and mediates the fusion of viral envelope and cell membrane by its hydrophobic function, resulting in cell destruction. Its mechanisms are not yet fully understood and may work in the following ways. 1. Because the HIV envelope protein inserts the cell, or the virus sprouts the release to cause the cell membrane permeability to increase, produces the osmotic dissolution. 2. The membrane of the organelles fused with the CD-GP120 complex in the infected cells, which led to the rapid death of infected cells. 3. The accumulation of unintegrated DNA or the inhibition of cell protein during HIV infection leads to the killing effect of HIV. 4. GP120 expressed in HIV-infected cells can bind to CD4 on the uninfected cell membrane and fuse to form multinucleated giant cells under the action of GP41. 5. The HIV-infected cell membrane virus antigen binds to specific antibodies and lyses the cells by activating the complement or mediating the AGCC effect. 6. HIV induces autoimmunity. For example, there is a homologous region between GP41 and MHC2 molecules on a T4 cell membrane, and the anti-GP41 antibody can cross-react with these lymphocytes and lead to cell destruction. 7. Programmed cell death. The activation of apoptosis during the onset of AIDS. For example, GP120 of HIV binds to CD4 receptor and directly activates apoptosis of infected cells. Even the enveloped antigen expressed by T cells infected with HIV can activate the normal T cells and indirectly destroy the apoptotic CD4 cells through the cross-linking of CD4 molecules on the surface of the cells, resulting in severe immune deficiency centered on the defect of T4 cells. At present, there are four forms of HIV vaccine. The first is levotenuated and inactivated vaccines. Vaccines of intact virions can induce an immune response similar to a real viral infection. Both levotenuated virus vaccines and inactivated virus vaccines have shown abilities to provide immunity in non-human prionates. Formalin-inactivated simian immunodeficiency virus is capable of inducing protection against the live virus in most immunized macaques. The NEF-deleted SIV vaccine could induce complete protection in monkeys. The attenuated SIV strain, SHIVNAC293-Delta-3, which deleted the NEF and BPR genes, also produced a protective effect, but the immune response provided is not long enough. The second is protein subunit vaccines. Protein subunit vaccines GP140, GP160, GP120 are capable of producing neutralizing antibodies and activating CD4 positive T cells, but their drawback is that they cannot produce CTL responses. The AIDS-VAX B-slash-B vaccine prepared using the HIV-1-CLAID-B-GP120 protein and the CLAID-B isolate showed good safety and immunogenicity in phase I and phase II clinical trials. However, the vaccine and another vaccine that passed phase II clinical trials, AIDS-VAX-B-E, did not provide protection against HIV infection. The third is live recombinant vaccines. HVTN-502 is a replication-defective recombinant adenovirus type V vaccine that expresses the NEF-GAG-PAL protein of HIV-1-CLAID-B. It has been found in clinical studies that the vaccination group still has a high infection rate. The researchers believe that the reason for this result may be that RAD5 may form a complex with its neutralizing antibodies and promote HIV infection of CD4 positive T cells. ALBOT's HIV-BCP1521 is a non-replicating recombinant canarypox virus capable of expressing the GAG-SLASH goal of HIV-CLAID-B and the ENT protein of CRFO1-A. The strategy of this vaccine is to use a live virus vector vaccine for primary immunization and then use protein for booster immunization to obtain both cellular and humoral immune responses. Clinical trials showed that the vaccine was 61 percent protective after one year of inoculation, but the proportion dropped to half at the end of the trial. The last is DNA vaccines. The vaccination strategy for HIV DNA vaccines is to immunize animals with DNA vaccine for a prime vaccination, followed by a heterogeneous boost or co-inoculation with the same antigen administrated by another vehicle. HIV challenges the standard vaccine approaches first and foremost because, unlike diseases such as measles and chickenpox, no one naturally recovers from infection with HIV. If a person is infected with measles and survives, the immune response to the infection will usually be sufficient to prevent future infection with the measles. Researchers can use this naturally derived immunity as a model for the level of protection a successful vaccine should provide. Without a model for natural immunity, researchers do not have a way to identify an immune response that would be effective against HIV, and thus, developing an HIV vaccine is much more difficult. A second challenge in developing a vaccine is that HIV mutates frequently. These frequent changes in the virus make it a difficult moving target for a vaccine. Additionally, there are many subtypes of HIV, each of which is genetically distinct. It's likely that additional subtypes will continue to emerge. This poses yet another challenge, as a vaccine that protects against one subtype may not provide protection against others. A third challenge, related to the first is that researchers have not been able to determine what is known as the correlative protective immunity to HIV infection. A correlative protective immunity is defined as a specific immune response that is closely related to protection against infection, disease, or other defined endpoint. Because no one is known to have been infected with HIV and then naturally cleared the virus, we do not know what protection from HIV would look like in a person. Would it be production of a certain kind and number of antibodies? Would it be the persistence of a certain kind of memory T cell? Until researchers have established what the correlates of protective immunity to HIV infection are, designing and validating a vaccine will be difficult. Finally, animal models are an important tool in understanding the basic pathway of infection and immune system response in most diseases as well as in vaccine research. However, there is no reliable, non-human animal model for HIV infection and immune system response. HIV vaccine tests in animals have not yet yielded accurate predictions of how the vaccines will work in humans. Researchers continue to perform trials testing vaccines against simian immunodeficiency virus, the monkey virus related to HIV, and against genetically engineered hybrids of civ and HIV in hopes of using similar approaches against HIV. Creative Biolabs is an excellent vaccine development and serving company. The company not only has a lot of achievements in the innovative research and development of vaccines, but also continuously delivers its advanced technologies and experience to customers all over the world. We have an integrated research and development system and a complete service process. We can provide you with strategies for vaccine development and help you evaluate and optimize the immunogenicity of your vaccine, as well as any other products and services related to vaccine research.