Vaccine development has been in vain, new drug therapies have been emerging to fight "AIDS" for 40 years, and there is more hope if there are setbacks

There are many long-acting preparations for the treatment of AIDS on the market in the world, which can reduce the frequency of dosing and allow the drugs to exert their effects in the human body for a long time

December 1st is the 34th "World AIDS Day".

Highly potent antiretroviral drugs have transformed AIDS from a fatal disease into a treatable but incurable chronic disease; broad-spectrum neutralizing antibodies that block HIV before cells infect are already in clinical trials Experiments and explorations; but the research on AIDS vaccines has been "difficult to give birth", and efforts have been unsuccessful

Suppressing AIDS with long-acting agents is the trend

"AIDS virus (HIV) specifically infects human CD4+ T lymphocytes, thereby destroying the body's immune function and causing various complications, such as various bacterial, fungal or viral infections and hematological tumors

"Currently high-efficiency antiretroviral drugs can be divided into 7 categories, including nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, fusion inhibitors, CCR5 inhibitors "Dong Li, chief physician of the Department of Infectious Diseases of Jiangsu Provincial People's Hospital (The First Affiliated Hospital of Nanjing Medical

"The use of long-acting preparations to suppress AIDS is the future development trend

At present, there are many long-acting preparations for the treatment of AIDS in the world, such as cabotevir and rilpivirine

Aikoning is a synthetic peptide drug designed to target HIV membrane protein gp41.

"But these long-acting preparations are only used as therapeutic drugs, and there is currently no long-acting drug for pre-exposure prophylaxis in high-risk groups of AIDS

But not long ago, ViiV Healthcare, a subsidiary of GlaxoSmithKline, announced that the U.

AIDS vaccine development faces multiple challenges

"Since the first AIDS case was discovered in 1981, mankind has realized that the AIDS vaccine is one of the most effective means to end the AIDS epidemic

In 1981, AIDS was discovered and reported for the first time in humans, and the AIDS virus was isolated two years later, but the development of vaccines has been stagnant since then

"There are many types of AIDS vaccines, including inactivated vaccines, live attenuated vaccines, protein subunit vaccines, synthetic peptide vaccines, DNA vaccines, vector vaccines, etc.

"Because of the extremely high variability of HIV, the direction of mutation of the attenuated virus in the live attenuated vaccine cannot be predicted in the body, and there is a risk of retrovirus integration into the host DNA and reversion to wild-type

Why is the AIDS vaccine so "difficult to deliver"? "This is because HIV mutates too fast

The lack of ideal animal models is another important reason hindering vaccine development

Fu Gengfeng introduced that simian immunodeficiency virus (SIV) is very similar to HIV in terms of infection, transmission and incubation period.
The researchers successfully established a chimeric virus (SHIV) infection in non-human primate models
.
However, SHIV infection mode, dose, and time parameters can significantly affect vaccine evaluation results
.

"In addition, it is still unclear how HIV escapes the surveillance of the human immune system, which also brings challenges to vaccine development,
" said Fu Gengfeng
.

Antibody therapy has been used in clinical treatment trials

In the process of "fighting wits and courage" with AIDS, human beings have discovered a "guardian" with specific effects against HIV-broad-spectrum neutralizing antibodies
.
It can identify areas on the surface of HIV strains that are not prone to change, so that it has the ability to capture multiple strains, inhibit virus replication in patients, and effectively reduce HIV levels in the human body
.

"Broad-spectrum neutralizing antibodies are mainly isolated and purified from the blood of infected people.
They can directly neutralize HIV strains, prevent the virus from invading immune cells, and can also stimulate other immune cells in the body after neutralizing the virus to jointly destroy the virus or Cells infected by viruses
.
" Wu Jie, a professor at the School of Life Science and Technology, China Pharmaceutical University, told the Science and Technology Daily reporter that antiretroviral drugs inhibit and interfere with HIV after entering human infected cells, while broad-spectrum neutralizing antibodies are in Blocking is performed before the virus infects cells
.

However, it is very difficult for this kind of weapon to kill HIV to be produced in the body of HIV-infected patients.
Fu Gengfeng said, "Only 10%-15% of people infected with HIV can produce neutralizing antibodies, and only 2%-5% of patients have broad-spectrum HIV infection.
These broad-spectrum neutralizing
antibodies generally appear 2-3 years after the patient is infected with the virus, and can neutralize most HIV strains at very low concentrations.
The viral load in these people is very low, and they do not develop disease.
For the 'elite' controller
.
" Fu Gengfeng said
.

Studies have shown that the production of broadly neutralizing antibodies may be related to factors such as viral load, virus diversity, infection time and host immune status
.

"At present, it takes time to study broadly neutralizing antibodies in humans.
For example, the mechanism of its production is not fully understood.
There are some clinical trials trying to induce broadly neutralizing antibodies in humans to make vaccines, but now It hasn't worked yet
," Tang Huamin said
.

The good news is that in recent years, with the advancement and wide application of high-throughput neutralizing antibody screening and monoclonal antibody separation technology, researchers have successfully isolated hundreds of broad-spectrum neutralizing antibodies from infected individuals
.

On March 7, 2018, the FDA officially approved the first clinically applicable monoclonal antibody, which binds to CD4, the main receptor for HIV on the surface of T cells, to prevent these cells from being invaded by the virus
.

Relevant experts from the Chinese Center for Disease Control and Prevention of STD and AIDS Prevention and Control said that more and more antibodies have been used in clinical trials to explore
.

"In addition, scientists also use reverse vaccinology technology to actively search for immunogens that can stimulate the body to produce protective HIV-specific antibodies, and try to use viral vector vaccines, which carry genes that express antibodies, to induce the body to produce antibodies.
It provides new ideas and new technologies for AIDS vaccine research and development
.
" Wu Jie said
.