HIV vaccine
30 years later
Copper news
According to WHO, 60 million people have been infected with HIV all over the world, more than 36 million of them have died from the effects of infection, and another 35.3 million people are living with HIV infection today. The human immunodeficiency virus was independently discovered in 1983 in two laboratories: The Pasteur Institute in France under the leadership of Luc Montagnier and the National Cancer Institute in the USA under the leadership of Robert Gallo. Since then, many attempts have been made to create medicines that would cure HIV infection, but so far no such remedy has been found.
Nevertheless, thanks to effective treatment with antiretroviral drugs, the virus can be controlled and before an HIV-infected person develops AIDS, not a single decade can pass.
Development of HIV vaccines in the worldIn recent years, there have been many statements about the development of various vaccines to protect against HIV infection.
These vaccines are at different stages of development.
For example, clinical trials of an HIV vaccine called AIDSVAX, developed by the American company VaxGen, showed at an early stage that it does not produce enough antibodies and does not prevent infection with the virus. In this regard, studies of the drug were completed ahead of schedule in 2003.
The ALVAC-HIV vaccine, developed by the French pharmaceutical company Sanofi-Pasteur, was a weakened vaccine strain of the canary pox virus, in whose genome three HIV genes encoding its proteins are embedded. It was expected that delivered using a viral vector into human cells, these genes would stimulate the production of killer T-lymphocytes specific to HIV, that is, intended for its destruction. The results of stage II clinical trials of ALVAC-HIV published in July 2008 showed that when it was used, the number of HIV-specific T-killers in the blood of patients did increase, but to an insufficient extent.
The RV 144 vaccine, in which the drug AIDSVAX, which stimulates the humoral link of immunity (antibody production), was combined with ALVAC-HIV, which activates cellular immunity, was able to protect about 30% of volunteers from infection. This vaccine has reached the late stages of clinical trials, but has also not been approved due to insufficient efficacy.
American scientists have interrupted clinical trials of an HIV vaccine due to its ineffectiveness. The second phase of clinical trials called HVTN 505 has been conducted since 2009 under the auspices of the American National Institute of Allergy and Infectious Diseases (National Institute of Allergy and Infectious Diseases). The studies involved 2,504 people with HIV-negative status. During the experiment, the human immunodeficiency virus appeared in 41 volunteers who received the vaccine and in 30 people who received a placebo. As it turned out, the use of the drug not only does not reduce the risk of HIV infection, but also increases it.
Clinical trials of the Merck vaccine, in which 3,000 volunteers participated, turned out to be a failure: it turned out that the use of the drug also increases, not reduces, the risk of HIV infection, but also its.
Scientists from Duke University School of Medicine managed to get closer to creating a universal HIV vaccine, for the first time not only tracking the process of origin, maturation and interaction with the virus in the blood of an infected person neutralizing broad–spectrum antibodies - special proteins of the immune system produced by the body to fight HIV, but also finding out the conditions under which it becomes possible to production and efficiency.
Last year, a group of scientists from Oregon Health & Science University reported on the successful use of a vaccine developed by them, consisting of a modified version of the monkey cytomegalovirus, in whose genome the genes of the highly pathogenic strain SIV are embedded. The results of the study showed that the vaccine was able to completely rid half of the experimental rhesus monkeys of the virus.
The first vaccine based on the whole genetically engineered inactivated human immunodeficiency virus (SAV001), developed in collaboration with Western University (Canada) and Sumagen Canada, successfully passed the first phase of clinical trials in the period from March 2012 to August 2013.
During the tests, no serious side effects were detected, however, it was found that antibodies against the HIV p24 antigen increased by 64 times, and antibodies against the gp120 antigen increased by 8 times. Antibodies to gp120 are so-called neutralizing broad-spectrum antibodies, which are associated with the potential for immune control of HIV infection. Now the researchers are ready to start phase II trials.
Among the new approaches, the most promising is the use of modified Ankara cowpox virus, adenoassociated virus and replicon of Venezuelan equine encephalitis, which are strong activators of the work of T-killers (cytotoxic T-lymphocytes) – cells of the immune system, which are the main component of antiviral immunity.
Domestic HIV vaccinesFor the first time in Russia, the idea that it is necessary to start work on creating a vaccine against HIV was formulated in 1994 at the All-Russian meeting "AIDS as a national security problem" organized by the Biomedical Center.
In 1997, the summit of the Eight industrialized countries with the participation of Russia was held in Denver (USA), at which it was decided to cooperate internationally in the development of an HIV vaccine.
The candidate vaccine was developed in St. Petersburg (DNA vaccine, responsible performer Biomedical Center, co-executor - GosNII OCHB) and Novosibirsk (polyepitope vaccine, developer – SSC "Vector"). Somewhat later, the recombinant protein as a vaccine was proposed by the Moscow Institute of Immunology. This period included laboratory development and animal testing.
The second period of development of HIV vaccine works in Russia includes 2007-2010. The work was carried out in accordance with the Decree of the Government of the Russian Federation No. 1905 of December 25, 2007 "On the allocation of federal budget funds for research, monitoring of the human immunodeficiency virus and strengthening the material and technical base of a number of institutions."
In 2006, the summit of the Eight industrially developed countries was held in St. Petersburg, at which Russia confirmed its commitment to international cooperation in the development of an HIV vaccine. The developers of the HIV vaccine at this stage were the SSC "Vector", the State Research Institute of OCHB, the Institute of Immunology, St. Petersburg State University and the NNIU Biomedical Center.
In the third period, from 2008 to 2010, three candidate vaccines developed in St. Petersburg, Moscow and Novosibirsk passed the first phase of clinical trials. In addition, in St. Petersburg, as a result of cooperation between St. Petersburg State University and the Biomedical Center, a cohort of patients with high HIV infection was created, necessary for testing candidate vaccines for effectiveness.
In 2007, the Russian government allocated one billion rubles for the development of a domestic vaccine against HIV infection. As a result, the specialists of the SSC "Vector" developed the drug "Kombivichvak", the staff of the Institute of Immunology of the FMBA of Russia – "VICHREPOL", and the DNA-4 vaccine was created in the Research Institute of Especially Pure Drugs together with St. Petersburg State University.
Last Monday, Novosibirsk virologists announced their readiness, if funding is available, to begin conducting the second phase of clinical trials of the experimental HIV vaccine "Combivichvak" developed by them. The second phase of clinical trials involves evaluating the efficacy and safety of the drug in patients with HIV infection.
The first phase of the clinical trial of the vaccine, which involves the participation of healthy volunteers, was completed in February 2012. According to Alexander Sergeev, who held the position of general director of Vector at that time, during the research, vaccination caused a response from both the humoral and cellular parts of the immune system, in which it surpassed analogues developed abroad. Sergeyev also noted that the first stage of testing showed good tolerance of the vaccine.
General Director of the Russian State Center of Virology and Biotechnology "Vector" (Novosibirsk) Valery Mikheev noted that with proper funding, the tests can be completed within one and a half to two years. According to Alexander Agafonov, Deputy General Director of Vector, this will require 200-300 million rubles.
The vaccine "Vichrepol", created at the Institute of Immunology, has now also completed the first phase of clinical trials with healthy volunteers, during which its safety was shown. Now the drug included in the International Register of Anti-HIV/AIDS Vaccine Trials is being prepared for the second phase of clinical trials.
Meanwhile, DNA-4-vaccine, a joint development of scientists from the St. Petersburg Biomedical Center and the State Research Institute of Especially Pure Biological Products of the FMBA of the Russian Federation, has already reached the second phase of clinical trials. According to scientists, studies of this drug will be completed in three to four years.
To date, the development of an HIV vaccine is recognized as one of the priorities in the world. Every year, countries allocate millions of dollars to solve it, conduct a lot of research, but the question of creating an effective vaccine that would prevent infection and the spread of infection is still open.
Portal "Eternal youth" http://vechnayamolodost.ru16.10.2014