Four seas network: AIDS is known as a super terminal disease, will not die immediately after the onset. But wait for HIV to slowly erode the body's immune cells, and finally let people die without any fight. In the past half century, the global research on AIDS vaccine has made little progress. Recently, however, some companies have dazzled, and the results of AIDS clinical trials show that 100% of the volunteers infected with AIDS have grown up with HIV antibodies, which means that AIDS will also be expected to be complete A radical cure!
Johnson & Johnson announced the results of the world's first human clinical trial of HIV vaccine on July 24. 393 healthy volunteers were recruited from the United States, Rwanda, Uganda, South Africa and Thailand in this multicenter, randomized, placebo-controlled, double-blind phase-1 / 2A clinical trial. The results showed that the volunteers were well tolerated by HIV vaccine and produced 100% anti HIV antibodies.
Single exposure to HIV reduced the risk of infection by 94%
Johnson & Johnson is the world's largest and diversified healthcare and consumer care product company. Its financial support is an important reason for the remarkable effect of the vaccine. The specific test is undertaken by its pharmaceutical company, Janssen, but the technology comes from Harvard University Medical School and other research units.
This HIV vaccine is a mosaic vaccine, that is, using a variety of HIV antigens (gene fragments) together to form a vaccine that has a strong stimulating effect on the body's immune system and can generate effective antibodies, called the approach vaccine. The approach vaccine is first and foremost exciting in its effectiveness. In addition to producing anti HIV antibodies in 100% of the subjects, it also reduced the risk of single exposure to HIV by 94%, and 66% of the subjects were still protected from HIV infection after six exposures.
In the vaccine trial, the strategy of "primary immunization - enhanced immunization" was adopted, that is, the subjects received 4 times of vaccine injection in total, the first two shots were primary immunization, and the last two shots were enhanced immunization. 48 weeks after the injection, the subjects had no side effects, and blood tests showed that all the people had antibodies against HIV. The risk of HIV infection was reduced by 94% in the assessment of the actual protection of the subjects.
The main reason for the remarkable effect of the mosaic vaccine is to design the vaccine according to the characteristics of HIV. The most important thing is to use a variety of HIV antigens, that is, to select genes from different HIV subtypes. These HIV antigens are generated by the virus vector and form a vaccine containing multiple HIV antigens.
The mosaic vaccine was tested in animals a few years ago
AIDS mosaic vaccine has been developed several years ago and has been tested in animals. In 2013, researchers from Harvard Medical School who developed mosaic vaccine reported in the journal cell that they developed mosaic vaccine using three major proteins of HIV.
The main reason to make a vaccine by splicing or inlaying several HIV genes is that these antigens can stimulate the immune system of the body extremely effectively, and make the immune system produce a large number of antibodies against these antigens, so as to neutralize (resist) HIV and prevent HIV from invading human immune T cells.
At that time, researchers inoculated rhesus monkeys with the vaccine, and used the most pathogenic human monkey chimeric immunodeficiency virus (SHIV, similar to human immunodeficiency virus HIV) to infect rhesus monkeys naturally six times to test the effect of the vaccine. The results showed that only 3 of 12 rhesus monkeys inoculated with the vaccine were free from infection after six times of exposure to human simian chimeric immunodeficiency virus. However, compared with 12 rhesus monkeys (all infected after three times of exposure to human simian chimeric immunodeficiency virus), the protective effect of mosaic vaccine on rhesus monkeys was 87% to 90%.
Based on the results, researchers at Harvard University concluded that mosaic vaccine may not only be effective for humans, but also reduce the risk of HIV infection by about 90%. Now, Johnson & Johnson's Janssen Pharmaceutical Company's approach mosaic vaccine test on people has reduced the risk of human infection by 94%, indicating that the original hypothesis has been preliminarily tested.
How does mosaic vaccine come from?
Mosaic vaccine, also known as mosaic vaccine, is the core research of AIDS vaccine preferred by researchers in various countries after the large-scale clinical trial of RV144 AIDS vaccine in Thailand in 2009. At that time, large-scale research in Thailand showed that RV144 could only reduce the HIV infection rate by 31%, but it was the most effective vaccine.
It is not ideal that a vaccine can only protect 31% of people. At least 60% of people need to be protected to be called an effective vaccine. Later, after extensive and in-depth research, the researchers thought that the limited protective effect of RV144 vaccine was due to the insufficient effective stimulation of its antigen and the lack of representativeness of its antigen. Therefore, the focus of research and development shifted to the mosaic vaccine. The design and development of vaccine for a certain disease is certainly based on the characteristics, structure, transmission characteristics and targets of pathogens that cause the disease. Now, the design of HIV vaccine has transferred to the structural characteristics of HIV, because its structure is quite complex and has great variability.
If HIV is not the most complex virus in the world, it is also one of the most complex viruses. The International Committee on the classification of viruses divides HIV into two types: HIV-1 and HIV-2. At present, HIV-1 is the main cause of AIDS in the world. Hiv-2-induced AIDS is mainly prevalent in West Africa. The pathogenicity of HIV-2 is lower than that of HIV-1, and the transmission speed is slower than that of HIV-1. HIV-1 and HIV-2 are very different in gene sequence, and their coated glycoprotein often can not cause cross immune response. Therefore, the current development of AIDS vaccine is mainly for HIV-1 vaccine.
Even HIV-1 has many subtypes. The structure of HIV is very complex and there are many subtypes. If only a single subtype and one or two of its genes are selected as the anti original vaccine, even if the human immune system can produce antibodies, it is only antibodies against one or two antigens, which is not enough to cause a fatal blow to HIV. The virus can also survive and infect human immune T cells.
Therefore, not only in clinical treatment, especially in vaccine development, clinicians and researchers pay special attention to HIV caused by different genotypes. At the same time, it also formed the core idea of developing HIV vaccine, that is, to use all the antigen components of HIV as much as possible. However, this is an ideal requirement, which is difficult to achieve at present, so we can only go back to the next step and use multiple antigens of HIV. And the experiments on volunteers also need to be diverse and global. Only when the experiments on national volunteers in different regions of the world get results, can we prove that a vaccine has broad-spectrum resistance (effectiveness). This is the case with the approach mosaic vaccine.
Mosaic vaccine development also has strong competition
The research and development of AIDS vaccine is like the research and development of other products, competition is a normal situation. Therefore, Johnson & Johnson and Harvard University are not the only companies targeting mosaic vaccine. Other research institutions and researchers are also developing mosaic vaccine.
Before J & J, the vaccine cancer immunotherapy company of the United States held the spring group meeting of HIV vaccine trial network in Washington in May this year. Dr. Rosa, assistant professor of the University of Washington Medical Laboratory and Fred middot Hutchinson Cancer Research Center, announced the results of the first clinical study of the HIV vaccine pennvax GP developed by the team, which was also quite encouraging Dancing hearts, the pennvax GP vaccine also produced nearly 100% anti HIV antibodies, known as the highest overall immune response rate observed in human clinical trials (before the results of Johnson & Johnson).
Pennvax GP is also a mosaic vaccine, using four antigens of HIV, one more than the mosaic vaccine tested by Johnson & Johnson. The vaccine cancer immunotherapy company recruited 94 volunteers to participate in the pennvax GP vaccine trial, 85 of whom were vaccinated and 9 received placebo.
Pennvax GP, the mosaic vaccine of vaccine cancer immunotherapy company, is more detailed and hierarchical than the mosaic vaccine of Johnson & Johnson company. However, there are less than 100 subjects, and nearly 400 subjects of Johnson & Johnson company, so it is more convincing in the experimental effect.
Although the above two mosaic vaccines have shown encouraging results, more trials are still needed to prove the effectiveness of the vaccine, at least in number similar to or equivalent to the HIV vaccine RV144 carried out in Thailand in 2009, when 15000 people participated in the trial.
On the other hand, although mosaic vaccine has become the mainstream and focus of AIDS vaccine at present, the research and development of AIDS vaccine is also "all roads lead to Rome", and other studies have shown excellent results. Even RV144 vaccine, which is regarded as a failure, has the possibility of "saltfish turning over". For example, researchers at the school of medicine at Case Western Reserve University in the United States retested rhesus monkeys with RV144 vaccine combined with alum adjuvant, and found that they could reduce the risk of HIV infection by 44%, which is 13 percentage points higher than the risk of 31% reduction in human studies in 2009.
It seems that the progress of AIDS vaccine research and development is encouraging, and it is likely to be at the critical point of breakthrough.