According to the WHO, there are currently more than 36 million people infected with the human immunodeficiency virus (HIV) and 2.4 million more people are infected each year. Despite all the success of medical treatment against the virus, an effective vaccine is of utmost importance. In collaboration with international colleagues, researchers from the German Primate Center (DPZ) - Leibniz Institute for Primate Research have tested a new vaccination strategy against simian immunodeficiency virus (SIV) in rhesus monkeys . For this, the researchers used a vaccine composed of two components. The monkeys were immunized subcutaneously, orally and intramuscularly with a delay and alternately. Scientists were able to show that the type of booster vaccine, oral and intramuscular, as well as the order of the vaccine components, influenced the immune system activation. These represent essential factors in the long-term prevention of SIV infection. As SIV and HIV replicate primarily in the body's own activated CD4 + T cells that are essential for immune defense, it is crucial that their levels remain relatively low even after vaccination. In order to obtain sustained protective immunity against AIDS, a vaccination strategy inducing a balanced immune response without an increase in CD4 + helper T cells must be developed ( Journal of Virology ).
There are several reasons for the lack of a vaccine against HIV infection. Unlike conventional vaccines, the (active) HIV agent must trigger an immune response strong enough to ensure that no cells will be infected, otherwise the virus will be permanently integrated into the genome of the cells. . This is not necessary with other vaccines because most viruses are not firmly anchored in the genome. To do this, a vaccine response faster than the spread of the virus and able to stop cell damage is sufficient.
Another hurdle for an AIDS vaccine is the immune system itself. For the body's immune system to trigger an optimal immune response, CD4 + helper T cells are needed. The dilemma of vaccine research is that these cells are also the target cells for HIV or SIV infection. As part of an international cooperation with Italian and Austrian partners, an American research group and German experts from Erlangen, Bochum and Kiel, Ulrike Sauermann and Christiane Stahl-Hennig, scientists from the United States. Unit of the German Primate Center infection models, have tested a vaccine approach that takes into account these critical factors.
The researchers administered a potential vaccine consisting of two components to twelve rhesus monkeys that served as an animal model for human infection with HIV. The administration of a compound vaccine is called a booster vaccination. In the initial stage, all monkeys were treated with genetically modified SIV, which infected the host cells, but was unable to replicate in the body. This procedure serves as an "initial stimulant" of the immune system (priming). The monkeys were then divided into two groups, where they then received the second vaccination component consisting of two different viral vectors by different routes.
Non-pathogenic vectors serve as gene shuttles for transporting SIV components, such as envelope proteins, into target cells. This second step increases the immune response (boost). In the first step, six monkeys received an adenoviral gene shuttle, which was administered orally as a spray. In the second step, they received an intramuscular injection with a Fowlpox virus genetic shuttle. For the other six monkeys, the scientists reversed the process. In this group, the Fowlpox vector was first administered orally followed by the adenovirus vector as an injection. Following this, the monkeys had weekly intervals of exposure to low doses of SIV, which triggers an AIDS-like illness. This process continued until almost all the monkeys were infected.
"We observed that the virus of all vaccinated animals initially replicated less than in the control group," summarized Ulrike Sauermann, first author of the study. "This shows that the vaccine induced a protective response in immunized monkeys. In the second group treated with Fowlpox vector and then with the adenovirus vector, the probability of infection was reduced by about 70%, Against only In addition, the CD4 + T helper cells were less activated in the second group. "
The data show that the order and type of administration (oral spray or injection) vaccines can affect the activation of the immune system and may have a long-term effect that affects immunizations subsequent as well as susceptibility to infection. It is therefore important to find a balance between the helper T cell response and the remaining immune responses. Excessive activation of CD4 + T helper cells may reverse the protective immune response.
"The results of an earlier study on the AIDS vaccine have shown that in the worst case, the immunization against HIV could reinforce the infection," says Christiane Stahl-Hennig, who said designed the project in collaboration with the former employee of DPZ Sieghart Sopper. ]
"Even though a comparable monkey vaccination strategy has failed before, the study was nonetheless conducted in humans in order to identify and avoid the potential risks of vaccination Against AIDS, it is essential to plan and execute carefully We believe that we have found an effective component for a compound vaccine. Immunization by SIV components in an avian plague vector seems to be safe and promising.In the course of follow-up experiments, our goal is to improve booster immunization in order to achieve even higher efficiency and protection rates. "
Source:
http://www.dpz.eu/en/home/single-view/news/neue-impfstrategie-gegen-aids-getestet-1.html
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