SAV001-H is the first candidate preventive HIV vaccine using a killed or "dead" version of the HIV-1 virus (inactivated vaccine).
The vaccine was developed by Dr. Chil-Yong Kang and his research team at Western University’s Schulich School of Medicine & Dentistry in Canada.
The results of the Phase I clinical trial, completed in August 2013, showed no serious adverse effects in 33 participants.
The SAV001-H vaccine is considered to be the first whole killed genetically modified HIV-1 vaccine.
According to Dr. Kang, the HIV-1 strain was genetically engineered such that first, “the gene responsible for pathogenicity, known as nef” is removed to make it non-pathogenic. Then, the signal peptide gene is replaced with a honey bee toxin (melittin) signal peptide to make the virus production much higher and faster. [1] In the signal peptide exchange process, another gene called vpu is lost due to an overlapping. [2] Finally, this genetically modified version of HIV-1, (i.e., HIV-1 virus with nef negative, vpu negative and signal peptide gene replaced with those of a honey bee) is grown in human T-lymphocytes (A3.01 cell line), collected, purified and inactivated by AT-2 (aldrithiol-2 or 2,2'-Dipyridyldisulfide) chemical treatment and gamma irradiation. AT-2 chemical treatment is used because it does not affect the viral structure and immunogens. [3]
The killed virus vaccine approach successfully prevents polio, influenza, cholera, mumps, rabies, typhoid fever and hepatitis A. At the moment, there are also 16 animal vaccines using the killed virus design. A vaccine against feline immunodeficiency virus (a virus related to HIV which infects cats) used the kills virus design - the vaccine was discontinued from production for multiple reasons, including commercial non-viability, protection not covering all FIV strains, and concerns over sarcoma at the injection site caused by adjuvants. [4]
Phase I clinical trial (NCT01546818) in HIV-infected individuals [5]
Funded by Sumagen Canada, the government of Canada and the Bill and Melinda Gates Foundation, [6] it started in March 2012 to assess its safety, tolerability, and immune responses. This was a randomized, double-blind, placebo-controlled trial, administering vaccine intramuscularly to 33 chronic HIV-1 infected individuals being treated with HAART.
The trial was completed in August 2013. It reported no serious adverse effects. The vaccine induced antibodies in participants. Antibodies against gp120 surface antigen and P24 capsid antigen increased up to 6-fold and 64-fold, respectively, and the increased level of antibody was continued throughout the 52-week study period. [7] Broadly neutralizing antibodies were found in some blood samples of the participants.
Phase II clinical trial
The Phase II clinical trial was expected to begin in 2018 [8] in the United States to measure immune responses. The researchers planned to recruit about 600 HIV-negative volunteers who are in the high risk category for HIV infections such as commercial sex workers, men who have sex with men (MSM), injecting drug users, and people who have unsafe sex with multiple partners.
Therapeutic HIV vaccine status
Dr. Kang has also developed a therapeutic HIV vaccine employing recombinant vesicular stomatitis viruses carrying of HIV-1gag, pol and/or env genes. Researchers reported that the therapeutic vaccine induced robust cellular immune responses in animal tests recently conducted. [9]
Although the whole killed virus vaccine strategy is successfully used worldwide to prevent diseases like polio, influenza, cholera, mumps, rabies, typhoid fever and hepatitis A, it did not receive serious attention in HIV vaccine development, for scientific, economic and technical reasons. First, there are risks associated with inadequately inactivated or not killed HIV remaining in vaccines. Second, massive production of HIV is not economically feasible, if not impossible. Third, many researchers believe that inactivating/killing HIV by chemical treatment also removes its antigenicity, so that it fails to induce both neutralizing antibodies and cytotoxic T-lymphocyte or CD8+ T cells (CTL). Fourth, early studies with monkeys using the killed simian immunodeficiency virus (SIV) vaccine showed some optimism but it turned out that the protection was attributable to responses to both the cellular proteins on the SIV vaccine and on the challenge virus grown not in monkey cells but in human cells. Fifth, lab-adapted HIV-1 seemed to lose envelope glycoprotein, gp120, during preparation. [10]
Nonetheless, many scientists and researchers believe that the whole killed virus vaccine strategy is a feasible option for an HIV vaccine. [11] [12] [13] Jonas Salk had developed a therapeutic whole killed HIV vaccine in 1987, called Remune, which is being developed by Immune Response BioPharma, Inc., [14] Remune vaccine completed over 25 clinical studies and showed a robust mechanism of action, restoring white blood cell counts in CD4 and CD8 T cells by reducing viral load and increasing immunity.
The developer of SAV001-H, Dr. Chil-yong Kang, is a professor of Virology in the Department of Microbiology and Immunology, Schulich School of Medicine & Dentistry at the University of Western Ontario since 1992. In addition to HIV preventive and therapeutic vaccine candidates, Dr. Kang is developing a second generation vaccine against hepatitis B and hepatitis C virus.
The patents related to the SAV001 vaccine were registered in more than 70 countries, including the U.S., the European Union, China, India, and South Korea. [15]
Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Antiviral drugs are a class of antimicrobials, a larger group which also includes antibiotic, antifungal and antiparasitic drugs, or antiviral drugs based on monoclonal antibodies. Most antivirals are considered relatively harmless to the host, and therefore can be used to treat infections. They should be distinguished from virucides, which are not medication but deactivate or destroy virus particles, either inside or outside the body. Natural virucides are produced by some plants such as eucalyptus and Australian tea trees.
An HIV vaccine is a potential vaccine that could be either a preventive vaccine or a therapeutic vaccine, which means it would either protect individuals from being infected with HIV or treat HIV-infected individuals. It is thought that an HIV vaccine could either induce an immune response against HIV or consist of preformed antibodies against HIV.
Feline immunodeficiency virus (FIV) is a Lentivirus that affects cats worldwide, with 2.5% to 4.4% of felines being infected.
A cancer vaccine, or oncovaccine, is a vaccine that either treats existing cancer or prevents development of cancer. Vaccines that treat existing cancer are known as therapeutic cancer vaccines or tumor antigen vaccines. Some of the vaccines are "autologous", being prepared from samples taken from the patient, and are specific to that patient.
This is a list of AIDS-related topics, many of which were originally taken from the public domain U.S. Department of Health Glossary of HIV/AIDS-Related Terms, 4th Edition.
Original antigenic sin, also known as antigenic imprinting, the Hoskins effect, immunological imprinting, or primary addiction is the propensity of the immune system to preferentially use immunological memory based on a previous infection when a second slightly different version of that foreign pathogen is encountered. This leaves the immune system "trapped" by the first response it has made to each antigen, and unable to mount potentially more effective responses during subsequent infections. Antibodies or T-cells induced during infections with the first variant of the pathogen are subject to repertoire freeze, a form of original antigenic sin.
Following infection with HIV-1, the rate of clinical disease progression varies between individuals. Factors such as host susceptibility, genetics and immune function, health care and co-infections as well as viral genetic variability may affect the rate of progression to the point of needing to take medication in order not to develop AIDS.
The Division of Acquired Immunodeficiency Syndrome (DAIDS) is a division of the National Institute of Allergy and Infectious Diseases, which is part of the National Institutes of Health. It was formed in 1986 as a part of the initiative to address the national research needs created by the advent and spread of the HIV/AIDS epidemic. Specifically, the Division's mission is to increase basic knowledge of the pathogenesis, natural history, and transmission of HIV disease and to support research that promotes progress in its detection, treatment, and prevention. DAIDS accomplishes this through planning, implementing, managing, and evaluating programs in (1) fundamental basic research, (2) discovery and development of therapies for HIV infection and its complications, and (3) discovery and development of vaccines and other prevention strategies.
Entry inhibitors, also known as fusion inhibitors, are a class of antiviral drugs that prevent a virus from entering a cell, for example, by blocking a receptor. Entry inhibitors are used to treat conditions such as HIV and hepatitis D.
CD4 immunoadhesin is a recombinant fusion protein consisting of a combination of CD4 and the fragment crystallizable region, similarly known as immunoglobulin. It belongs to the antibody (Ig) gene family. CD4 is a surface receptor for human immunodeficiency virus (HIV). The CD4 immunoadhesin molecular fusion allow the protein to possess key functions from each independent subunit. The CD4 specific properties include the gp120-binding and HIV-blocking capabilities. Properties specific to immunoglobulin are the long plasma half-life and Fc receptor binding. The properties of the protein means that it has potential to be used in AIDS therapy as of 2017. Specifically, CD4 immunoadhesin plays a role in antibody-dependent cell-mediated cytotoxicity (ADCC) towards HIV-infected cells. While natural anti-gp120 antibodies exhibit a response towards uninfected CD4-expressing cells that have a soluble gp120 bound to the CD4 on the cell surface, CD4 immunoadhesin, however, will not exhibit a response. One of the most relevant of these possibilities is its ability to cross the placenta.
GeoVax is a clinical-stage biotechnology company which develops vaccines. GeoVax's development platform uses Modified Vaccinia Ankara (MVA) vector technology, with improvements to antigen design and manufacturing capabilities. GeoVax uses recombinant DNA or recombinant viruses to produce virus-like particles (VLPs) in the person being vaccinated.
An inactivated vaccine is a vaccine consisting of virus particles, bacteria, or other pathogens that have been grown in culture and then killed to destroy disease-producing capacity. In contrast, live vaccines use pathogens that are still alive. Pathogens for inactivated vaccines are grown under controlled conditions and are killed as a means to reduce infectivity and thus prevent infection from the vaccine.
A neutralizing antibody (NAb) is an antibody that defends a cell from a pathogen or infectious particle by neutralizing any effect it has biologically. Neutralization renders the particle no longer infectious or pathogenic. Neutralizing antibodies are part of the humoral response of the adaptive immune system against viruses, bacteria and microbial toxin. By binding specifically to surface structures (antigen) on an infectious particle, neutralizing antibodies prevent the particle from interacting with its host cells it might infect and destroy.
Peptide-based synthetic vaccines are subunit vaccines made from peptides. The peptides mimic the epitopes of the antigen that triggers direct or potent immune responses. Peptide vaccines can not only induce protection against infectious pathogens and non-infectious diseases but also be utilized as therapeutic cancer vaccines, where peptides from tumor-associated antigens are used to induce an effective anti-tumor T-cell response.
A microantibody is an artificial short chain of amino acids copied from a fully functional natural antibody. Microantibodies can stop viruses such as HIV from infecting cells in vitro.
MVA-B, or Modified Vaccinia Ankara B, is an HIV vaccine created to give immune resistance to infection by the human immunodeficiency virus. It was developed by a team of Spanish researchers at the Spanish National Research Council's Biotechnology National Centre headed by Dr. Mariano Esteban. The vaccine is based on the Modified vaccinia Ankara (MVA) virus used during the 1970s to help eradicate the smallpox virus. The B in the name "refers to HIV-B, the most common HIV subtype in Europe". It has been stated by Dr. Esteban that, in the future, the vaccine could potentially reduce the virulence of HIV to a "minor chronic infection akin to herpes".
HIV/AIDS research includes all medical research that attempts to prevent, treat, or cure HIV/AIDS, as well as fundamental research about the nature of HIV as an infectious agent and AIDS as the disease caused by HIV.
Bionor Holding AS is a Norwegian biotechnology company, developing vaccines targeted at rapidly mutating virus infections such as HIV, Hepatitis C and Influenza. The company is also a leader in soy technology and has developed patented products for improved health and prevention of lifestyle-related diseases. It was founded by Cand.med. and Dr.philos. in protein and lipid research, Lars Høie.
Anna-Lise WilliamsonMASSAf is a Professor of Virology at the University of Cape Town. Williamson obtained her PhD from the University of the Witwatersrand in 1985. Her area of expertise is human papillomavirus, but is also known on an international level for her work in developing vaccines for HIV. These vaccines have been introduce in phase 1 of clinical trial. Williamson has published more than 120 papers.
Remune was the first therapeutic HIV vaccine based on the killed whole virus approach. Remune was initially invented by Jonas Salk in 1987 and was developed by Immune Response BioPharma, Inc. (IRBP)