Johnson & Johnson announces the results of the world's first HIV vaccine test: 100% antibodies are produced

　

Johnson & Johnson announced the results of the world’s first human HIV vaccine clinical trial on July 24. This multi-center, randomized, placebo-controlled, double-blind Phase 1/2a clinical trial recruited 393 healthy volunteers. Volunteers were from the United States. , Rwanda, Uganda, South Africa and Thailand, the results showed that the volunteers tolerated the HIV vaccine well, and 100% produced antibodies against HIV.

Single exposure to HIV reduces the risk of infection by 94%

Johnson & Johnson is the world’s largest and diversified medical and health care products and consumer care product company. Its financial support is an important reason for the remarkable results of this vaccine. The specific trials are undertaken by its subsidiary Janssen Pharmaceuticals, but The technology comes from research units such as Harvard University Medical School.

The HIV vaccine this time is a mosaic vaccine, which uses multiple antigens (gene fragments) of HIV to combine to form a vaccine that has a strong stimulating effect on the body's immune system and can generate effective antibodies, called appROACH vaccine. The appROACH vaccine is first of all exciting in effect. In addition to 100% of the subjects produced antibodies against the HIV virus, the risk of infection under a single exposure to HIV (HIV) was reduced by 94%, and 66% of the subjects were exposed to 6 times. Still protected under HIV and not infected by HIV.

The vaccine trial adopted the strategy of "primary immunization-boost immunization", that is, the subjects received a total of 4 vaccine injections in the trial. The first two shots of the vaccine were primary immunizations, and the second two shots of vaccines were booster immunizations. 48 weeks after the injection, the subjects did not have any side effects, and blood tests found that all people had developed antibodies against HIV. In the assessment of the actual protection of subjects, the risk of HIV infection was reduced by 94%.

The significant effect of this AIDS mosaic vaccine is mainly due to the design of the vaccine according to the characteristics of HIV. The most important thing is the use of multiple antigens of HIV, that is, the selection of genes from multiple different HIV subtypes virus strains. These HIV antigens are produced by viral vectors. , Constitute a vaccine containing multiple HIV antigens.

Mosaic vaccine completed animal experiments a few years ago

The AIDS mosaic vaccine was developed a few years ago and tested on animals. In 2013, researchers at Harvard Medical School, who developed the mosaic vaccine, reported in the journal Cell that they developed a mosaic vaccine using the three main proteins of the HIV virus.

The main reason for splicing or mosaicing several HIV genes together to make a vaccine is that these antigens can stimulate the body’s immune system extremely effectively, and allow the immune system to produce a large number of antibodies against these antigens to neutralize (defend against ) AIDS virus, to achieve the purpose of preventing AIDS virus from invading human immune T cells.

At that time, the researchers tested the vaccine in rhesus monkeys, and used the most pathogenic human monkey chimeric immunodeficiency virus (SHIV, similar to human immunodeficiency virus HIV) to naturally infect rhesus monkeys with 6 simulations of HIV , To test the effect of the vaccine. The results showed that after the 12 vaccinated rhesus monkeys were exposed to human monkey chimeric immunodeficiency virus for 6 consecutive times, only 3 were protected from infection. However, compared with 12 rhesus monkeys in the unvaccinated control group (all infected after 3 exposures to human monkey chimeric immunodeficiency virus), the mosaic vaccine has a protective effect on rhesus monkeys as high as 87% to 90%.

Based on the results of this study, researchers at Harvard University concluded that the mosaic vaccine may not only be effective for humans, but may also reduce the chance of people being infected with HIV by about 90%. Now, the appROACH mosaic vaccine test conducted by Johnson Pharmaceuticals, a subsidiary of Johnson & Johnson, has reduced the risk of human infection by 94%, indicating that the original speculation has been tested by the trial.

How did the idea of ​​mosaic vaccine come from?

Mosaic vaccine, also known as mosaic vaccine, has become the first choice for AIDS vaccine core research by researchers from various countries after the large-scale clinical trial of AIDS vaccine RV144 conducted in Thailand in 2009. At that time, a large-scale study in Thailand showed that RV144 could only reduce the HIV infection rate by 31%, but it was already the most effective vaccine.

It is obviously not ideal that a vaccine can only protect 31% of people. At least 60% of people need to be protected before it can be called an effective vaccine. Later, after extensive and in-depth research, researchers believed that the protective effect of the RV144 vaccine was limited because of insufficient antigen stimulation and insufficient antigen representation. Therefore, the focus of research and development shifted to the mosaic vaccine. The design and development of a vaccine for a certain disease is of course based on the characteristics, structure, transmission characteristics of the pathogen that causes the disease, and the target target of the pathogen's attack. Now, the design of the AIDS vaccine has shifted to the structural characteristics of the AIDS virus, because its structure is quite complex and its variability is great.

If HIV is not the most complicated virus in the world, it is also one of the most complicated. The International Virus Classification Committee divides HIV into two major types: HIV-1 and HIV-2. At present, HIV-1 is the main cause of AIDS in all parts of the world. AIDS caused by HIV-2 is mainly prevalent in West Africa. HIV-2 is less pathogenic than HIV-1, and its spread is slower than HIV-1. HIV-1 and HIV-2 differ greatly in gene sequence, and their envelope glycoproteins often fail to cause cross-immune reactions. Therefore, the AIDS vaccines currently developed are mainly vaccines against HIV-1.

Even HIV-1 has many subtypes. The structure of HIV is very complex, with many subtypes. If only a single subtype and one of two genes are used as antigens to make a vaccine, even if the human immune system can produce antibodies, it will only target one or two antigens. The antibodies are not enough to cause a fatal blow to the HIV virus. The virus can also survive and infect human immune T cells.

Therefore, not only clinical treatment, especially in vaccine development, clinicians and researchers pay special attention to AIDS caused by different genotypes of HIV. At the same time, the core idea of ​​developing AIDS vaccines has also been formed, that is, it is necessary to use all the antigenic components of HIV as much as possible. However, this is an ideal requirement, which is currently difficult to achieve, so we can only take the next step and use a variety of HIV antigens. In addition, trials on volunteers also need to be diverse and global. Only when the results are obtained on volunteers from different regions of the world, can a vaccine be proven to have broad-spectrum resistance (effectiveness). This is the case with this appROACH mosaic vaccine.

Mosaic vaccine development also has strong competition

The research and development of AIDS vaccine is the same as the research and development of other products, competition is a normal state. Therefore, it is not only Johnson & Johnson and Harvard University that are targeting mosaic vaccines. Other research institutions and researchers are also developing mosaic vaccines.

Prior to Johnson & Johnson, the American Vaccine- Cancer Immunotherapy Company held the AIDS Vaccine Trial Network Spring All-Group Meeting in Washington in May this year. It was hosted by Assistant Professors of the University of Washington Medical Laboratory and Fred Hutchinson Cancer Research Center. Dr. Rosa announced the results of the first clinical study of the AIDS vaccine Pennvax-GP developed by the team, which is also quite encouraging. The Pennvax-GP vaccine also produced almost 100% antibodies against HIV. Before the company announces the results) the highest overall immune response rate observed in human clinical trials of the AIDS vaccine.

Pennvax-GP is also a mosaic vaccine, which uses 4 antigens of HIV, one more antigen than the mosaic vaccine tested by Johnson & Johnson. The vaccine-cancer immunotherapy company recruited 94 volunteers to participate in the Pennvax-GP vaccine trial, of which 85 were vaccinated and 9 were vaccinated with a placebo.

Vaccine-Cancer immunotherapy company's mosaic vaccine Pennvax-GP is more detailed and more hierarchical than Johnson & Johnson’s mosaic vaccine, but the test population is less than 100 people, while Johnson & Johnson’s subjects have nearly 400 people. , So it is more convincing in terms of experimental effects.

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 terms of numbers that are similar or equivalent to the AIDS vaccine RV144 conducted in Thailand in 2009, when Thailand conducted the AIDS vaccine RV144. 15,000 people participated in the trial.

On the other hand, although mosaic vaccine has become the mainstream and focus of current AIDS vaccines, the development of AIDS vaccines is also "all roads lead to Rome." Other studies have also shown good results, even RV144, which is considered a failure. Vaccines also have the possibility of "salted fish turning over". For example, researchers at Case Western Reserve University School of Medicine used the RV144 vaccine in combination with an alum adjuvant to retest rhesus monkeys and found that it can reduce the risk of HIV infection by 44%, which is 31 lower than the 2009 study on humans. % Risk increased by 13 percentage points.

From this point of view, the progress of AIDS vaccine research and development is encouraging, and it is indeed likely to be at the tipping point of breakthrough. (Original title "AIDS Vaccine Is Really Coming?")