Human immunodeficiency virus (HIV)
Human immunodeficiency virus (HIV)
198 1 year, the human immunodeficiency virus was first discovered in the United States. Viruses destroy human immunity, leading to the loss of immune system immunity, leading to the survival of various diseases and cancers, and finally leading to AIDS (acquired immunodeficiency syndrome). Nearly120,000 people died worldwide, and more than 30 million people were infected.
See also: AIDS
[Edit this paragraph] I. Biological diagnosis
(A) morphological structure
The virus is spherical with a diameter of 100 ~ 120 nm. Under the electron microscope, we can see that a compact conical core contains viral RNA molecules and enzymes (reverse transcriptase, integrase, protease). The outer envelope of the virus is a double-layer lipid protein membrane, and gp 120 and gp4 1 are embedded in the membrane to form spike protein and transmembrane protein respectively. The inner surface of the capsule is a capsid composed of P 17 protein, in which the core protein wraps RNA.
(2) Gene structure and function of encoded protein
The length of HIV gene is about 9.2 ~ 9.7 kb, including gag, Pol and env, and at least six regulatory genes (Tat Rev, Nef, Vif, VPU and Vpr), with long terminal sequences at the 5' and 3' ends of the genome. HIV LTR contains cis-regulatory sequences that control the expression of provirus genes. It has been proved that there are promoters and enhancers in LTR and negative regulatory regions.
1.gag gene can encode a polymer precursor protein composed of about 500 amino acids, which is hydrolyzed by protease to form P 17 and P24 nuclear proteins, so that RNA is not damaged by external nucleases.
2.POL gene encodes the precursor protein of polymerase, which is cleaved to form protease, integrase, reverse transcriptase and ribonuclease H, all of which are necessary for virus proliferation.
3.Env gene encodes a precursor protein with about 863 amino acids and glycosylates it into gp 160, gp 120 and gp4 1. Gp 120 contains neutralizing epitope, which has been proved that HIV neutralizes epitope. On the loop of gp 120 V3, the V3 loop region is an important functional region of envelope protein and plays an important role in the fusion of virus and cells. Gp 120 and transmembrane protein gp4 1 are linked by non-* * valence bonds. Gp4 1 fused with the target cell to promote the virus to enter the cell. Experiments show that gp4 1 also has strong antigenicity and can induce antibody reaction.
4. protein coded by 4. TaT gene can be combined with LTR to improve the transcription rate of all viral genes and promote the translation of viral mRNA after transcription.
5.Rev gene product is a cis-activating factor, which can inhibit cis-acting repressor sequence (CRS) in env and gag, enhance the expression of gag and env genes, and synthesize corresponding viral structural proteins.
6. number six. Nef gene encoding P27 protein negatively regulates the expression of HIV gene, thus delaying virus replication. This protein acts on the LTR of HIv cDNA and inhibits the integrated viral transcription. HIV may need to maintain a lasting sense of community in the body.
7.VIF gene is not necessary for HIV, but it may affect the infectivity of free HIV, the production of virions and the spread in vivo.
8.VPU gene is unique to HIV- 1, and it is necessary for effective HIV replication and virus body assembly and maturation.
9. protein coded by 9. Vpr gene is a weak transcription activator, which plays a certain role in the reproductive cycle in vivo.
The structure of HIV-2 gene is different from that of HIV- 1: it does not contain VPU gene, but has a VPX gene whose function is unknown. Nucleic acid hybridization showed that the nucleotide sequences of HIV- 1 and HIV-2 were only 40% identical. There is no cross reaction between the antibodies produced by env gene expression products stimulated by the body.
(3) Cultivation characteristics
When lymphocytes in patients' own peripheral or bone marrow were stimulated by PHA for 48-72 hours and cultured in vitro (IL-2 was added to the culture solution)/kloc-0 for 2 weeks, the virus could proliferate and be released outside the cells, and the cells merged into multinucleated giant cells, and finally the cells broke and died. It can also be used to isolate and subculture lymphocyte lines, such as HT-H9 and Molt-4 cells.
The infection range of HIV animals is narrow, only chimpanzees and gibbons, and chimpanzees are generally used for experiments. It is successful to infect chimpanzees with HIV filtrate infected with HIV cells or without cells, or to transfuse the blood of infected chimpanzees to normal chimpanzees. After 8 months, HIV was continuously isolated from blood and lymph, and after 3 ~ 5 weeks, HIV-specific antibodies were detected and maintained at a certain level. However, neither chimpanzees nor gibbons are infected with this disease.
(4) Resistance
HIV is sensitive to heat. It lost its activity at 56℃ for 30 minutes, but remained active after being stored at room temperature for 7 days. In the absence of stabilizer, the virus lost its activity when frozen at -70℃, but remained active when frozen at -70℃ for 3 months in 35% sorbitol or 50% fetal bovine serum. It is also sensitive to disinfectants and detergents. The 5' inactivated virus, 1%NP-40 and 0.5% Triton-X- were treated with 0.2% sodium hypochlorite, 0. 1% bleaching powder, 70% ethanol, 35% isopropanol, 50% ether, 0.3% H2O2 and 20.5% lysol. Strong resistance to ultraviolet rays and gamma rays.
[Edit this paragraph] 2. Viruses and immunity
(1) Source of infection and route of transmission
People infected with HIV are the source of infection. They have isolated HIV from blood, semen, vaginal secretions, tears and milk. Transmission routes are:
1. Sexual transmission: transmission through sexual contact between gay men and the opposite sex.
2. Blood transmission: Through blood transfusion, blood products or unsterilized syringes, intravenous drug users * * * use unsterilized syringes and needles to cause serious infection. According to China-Yunnan border, the infection rate of intravenous drug users is 60%.
3. Mother-to-child transmission: including transmission through placenta, birth canal and breastfeeding.
(2) Pathogenic mechanism
HIV selectively invades CD4 molecules, mainly including T4 lymphocytes, mononuclear macrophages and dendritic cells. CD4 molecules on the cell surface are HIV receptors, which bind to CD4 on the cell membrane through HIV envelope protein gp 120, and then penetrate into susceptible cells through gp4 1, causing cell destruction. Its mechanism is not completely clear, and it may play a role in the following ways:
1. Due to the insertion of HIV envelope protein into cells or the release of virus bud, the permeability of cell membrane increases, leading to osmotic dissolution.
2. The CD-gp 120 complex in infected cells fuses with the membrane of organelles (such as Golgi apparatus), leading to the rapid death of infected cells.
3. In the process of HIV infection, the accumulation of unconformity DNA or the inhibition of cell proteins lead to the killing effect of HIV on cells.
4.gp 120 is represented by 4. HIV-infected cells can combine with CD4 on uninfected cell membrane, fuse under the action of gp4 1 to form multinucleated giant cells, and then dissolve and die.
5.HIV-infected cell membrane virus antigen binds to specific antibody and lyses cells by activating complement or mediating ADCC effect.
6. HIV induces autoimmune. For example, gp4 1 shares the same region with MHC Ⅱ Ⅱ molecules on T4 cell membrane, and anti-gp4 1 antibodies can cross-react with such lymphocytes, leading to cell destruction.
7. Programmed cell death: Apoptosis can be activated during the onset of AIDS. For example, the gp 120 of HIV binds to CD4 receptor; Directly activate the apoptosis of infected cells. Even the envelope antigen expressed by HIV-infected T cells can activate normal T cells, and indirectly cause a lot of destruction of apoptotic CD+4 cells through the cross-linking of CD4 molecules on the cell surface, leading to serious immune deficiency centered on T4 cell defects. The main manifestations of patients are: peripheral lymphocytes decrease, T4/T8 ratio is distributed, the reaction to phytohemagglutinin and some antigens disappears, delayed allergic reaction decreases, NK cells and macrophages weaken, and the synthesis of cytokines such as IL-2 and IFN-γ decreases. In the early stage of the disease, due to the polyclonal activation of B cells, the level of lg in patients' serum often rises. With the progress of the disease, the function of B cells to produce antibodies against various antigens is also directly and indirectly affected.
AIDS patients are often complicated with serious opportunistic infections, such as cells (Mycobacterium avium), protozoa (Pneumocystis carinii, Toxoplasma gondii), fungi (Candida albicans, Cryptococcus neoformans) and viruses (cytomegalovirus, herpes simplex virus and hepatitis B virus), which eventually lead to uncontrollable death, and Kaposi sarcoma or malignant lymphoma may occur in other cases. In addition, the proliferation of HIV in infected mononuclear macrophages is low, which does not cause pathological changes, but damages its immune function, which can spread the virus to the whole body and cause interstitial pneumonia and subacute encephalitis.
After HIV infects the human body, it often takes a long incubation period (3-5 years or even more than 8 years) to get sick, which indicates that HIV persists in the infected body in the form of latent or low-level chronic infection. When the latent cells of HIV are stimulated by some factors, the latent HIV is activated and proliferated to cause disease, and most patients die within 1-3 years.
(3) Immunity
HIV infection can stimulate the body to produce antibodies against envelope protein (Gp 120, Gp4 1) and core protein (P24). Low levels of antiviral neutralizing antibodies were detected in the sera of HIV carriers and AIDS patients, with the lowest level in AIDS patients and the highest level in healthy homosexuals, indicating that antibodies have protective effects in the body. However, the antibody can't contact with the virus stored in monocytes and macrophages, which is prone to antigenic variation of HIV envelope protein, and the original antibody loses its function, which makes the neutralizing antibody unable to play its due role. In the latent infection stage, the pre-HIV virus is integrated into the genome of the host cell, which is not recognized by the immune system and escapes immune clearance. These are all related to the persistent infection caused by HIV.
[Edit this paragraph] III. Microbial diagnosis
The method of detecting virus antigen and antibody in body fluids of HIV-infected people is simple to operate and easy to popularize and apply, especially antibody detection. However, in the detection of HIv infection, the determination of HIv P24 antigen and virus gene has been paid more and more attention.
(1) antibody detection
There are mainly enzyme-linked immunosorbent assay (ELISA) and immunofluorescence assay (IFA). ELISA uses detergent to crack HIV or infected cell fluid extract as antigen, IFA uses infected cell smear as antigen for antibody detection, and if positive samples are found, the detection should be repeated. To prevent false positives, protein blot (WB) can be used for further confirmation.
WB method is to separate HIV protein by polyacrylamide gel electrophoresis, and then transfer different protein bands to nitrocellulose membrane by transfer electrophoresis. After incubation with patient serum, antibodies against different structural proteins, such as anti-gp 120, gp4 1 and P24, can be detected with high specificity.
(2) antigen detection
P24 antigen was detected by ELISA, and it existed in the blood before antibodies appeared in the early stage of HIV infection. Because the amount of P24 is too small, the positive rate is usually low. At present, the method of free immune complex or concentrating P24 antigen is used to improve the sensitivity.
(3) nucleic acid detection
Detection of HIV gene by PCR is rapid, efficient, sensitive and specific. At present, this method has been applied to the early diagnosis of HIV infection and the study of AIDS.
(4) Virus isolation
The commonly used method is * * * culture, that is, monocytes are isolated from normal peripheral blood, which are stimulated by PHA and then added to the diagnosis of patients' monocytes and the study of AIDS.
[Edit this paragraph] 4. Characteristics of HIV
HIV is the English abbreviation of HIV, and its characteristics mainly include the following points:
1, which mainly attacks the human T lymphocyte system.
2. Once it invades the cells of the body, the virus will be integrated with the cells, which will be difficult to eliminate for life.
3. Viral genes are very different.
4. It is widely found in blood, semen, vaginal secretions, saliva, urine, milk, cerebrospinal fluid and brain tissue fluid with neurological symptoms, and the highest concentration is in blood, semen and vaginal secretions.
5, the resistance to the external environment is weak, and the effective disinfection method for hepatitis B virus is also effective for HIV disinfection.
6. Infected people have a long incubation period and a high mortality rate.
7. The genome of HIV is more complex than any known virus gene.
[Edit this paragraph] V. "Window period"
After the human body is infected with HIV, it usually takes 2 weeks to gradually produce virus antibodies. "Window period" refers to the period from human infection with HIV to the detection of virus antibodies in peripheral blood, which is generally 2 weeks to 3 months. During this time, no virus antibody can be detected in the blood, but the human body is contagious. Only after the "window period" has passed will enough HIV antibodies be detected in the blood. However, it cannot be ignored that different individuals have different immune responses to HIV, and the time when antibodies appear is also different. Especially those who have high-risk behaviors recently, the infection cannot be easily discharged after a negative experimental result, and they should be checked again every 2-3 months.
[Edit this paragraph] VI. Indicates that you may have symptoms of AIDS.
Common symptoms of AIDS are:
(1) Persistent extensive lymphadenopathy, especially cervical, axillary and inguinal lymph nodes. The diameter of lymph node enlargement is about 1 cm, which is hard, painless and movable for more than three months.
(2) unexplained fever and night sweats for several weeks.
(3) Severe fatigue with unknown causes has occurred for several weeks.
(4) Loss of appetite, with weight loss exceeding 10% of original weight within 2 months.
(5) Unexplained chronic diarrhea with watery stools for several weeks, more than once a day 10.
(6) Shortness of breath and dry cough for several weeks.
(7) Flat and raised pink and purple spots appear on the skin and mouth, which is neither painful nor itchy.
(8) White spots appear in the throat. Scales and itching appear in male genitals. Female anal pruritus, vaginal itching, leucorrhea.
(9) Headache and blurred vision. When there are more than three symptoms and a history of unclean contact, you should go to the hospital for examination in time.
[Edit this paragraph] VII. Symptoms after HIV infection
In the early stage of HIV infection, also known as the acute stage, most of them are asymptomatic, but some people will have symptoms similar to influenza or infectious mononucleosis after a few days to three months of infection, such as fever, chills, joint pain, muscle pain, headache, sore throat, diarrhea, fatigue, night sweats and lymphadenopathy. Rash is a very common symptom. After that, they entered an asymptomatic infection period.
[Edit this paragraph] VIII. The duration of the incubation period or asymptomatic period of AIDS.
After HIV invades the human body, some people have flu-like or infectious mononucleosis-like symptoms, and some people have been asymptomatic and directly enter the asymptomatic period. The incubation period of AIDS varies greatly among individuals, which may be related to the type, intensity, quantity, infection route, immune function, health status, nutrition, age, living and medical conditions, psychological factors and so on. It usually takes 6- 10 years, but about 5- 15% people will progress to AIDS within 2-3 years, which is called rapid progress, and another 5% patients can maintain their immune function for more than 12 years, which is called long-term no progress.
[Edit this paragraph] 9. Disinfection method of AIDS virus
The resistance of HIV to the outside world is weak, far lower than that of hepatitis B virus. Therefore, the use of disinfection and inactivation of hepatitis B virus can completely deal with HIV. HIV is acid-resistant and alkali-resistant, and is insensitive to ultraviolet rays. Alcohol has a good inactivation effect on it. The international health organization recommended heating at 100℃ for 20 minutes to inactivate HIV, and the effect was satisfactory. The disinfection of HIV is mainly aimed at medical supplies and living places contaminated by blood and body fluids of HIV-infected people and AIDS patients. Such as ornaments, gauze, clothes, etc. The disinfection of HIV can choose the appropriate physical method or chemical method according to the disinfection project. Items that need to be reused can be disinfected by boiling or high-pressure steam. Articles unsuitable for boiling can be disinfected with 2% glutaraldehyde and 75% alcohol.
[Edit this paragraph] X. Institutions that can do HIV antibody testing
The centers for disease control (or health and epidemic prevention stations) of all provinces, autonomous regions and municipalities directly under the Central Government, frontier health and quarantine institutions, blood stations and blood centers at all levels, and hospitals with the qualification of initial screening for HIV antibody laboratory testing can all engage in HIV antibody testing. Other specific testing institutions, provinces, cities and districts can ask the above units. At present, most provinces and cities have confirmation laboratories, generally located in the provincial centers for disease control and prevention, which are responsible for the review and confirmation of positive specimens in this province. The above institutions provide HIV antibody testing and AIDS-related consultation, including telephone consultation, letter consultation and outpatient consultation.
[Edit this paragraph] XI. The reasons for the uncertainty of test results
(1) infection is still in the window period: the time from HIV entering the body to being detected is not long enough, so the serum has not yet formed a typical antibody reaction;
(2) When AIDS progresses to the terminal stage, the antibody level drops;
(3) HIV2 type 2 or other subtypes (such as O subtype) exist, and the detection reagents used cannot be detected;
(4) Antibody cross-reaction against other non-viral proteins: In the case of autoimmune diseases, some malignant diseases, pregnancy, blood transfusion or organ transplantation, the body can produce some antibodies, and the reaction is very similar to that caused by antibodies against HIVP24 core protein;
(5) I have been vaccinated with HIV (experimental) vaccine before.
If there are uncertain results, it is recommended to review after 3 months.
[Edit this paragraph] XII. Survival time of AIDS
The survival time of AIDS patients is closely related to the subtype virus they are infected with. Due to different subtypes of infection, the average survival time of AIDS patients varies greatly, although the number of infected viruses in these subjects is basically the same. The average survival time of patients infected with subtype A virus is 8.8 years, while the average survival time of patients infected with subtype D virus is reduced to 6.9 years, while the average survival time of patients infected with subtypes D and A virus is even shorter, with an average of only 5.8 years.
HIV in general blood can survive at room temperature 15d.
[Edit this paragraph] XIII. Conditions for the survival of HIV
HIV is sensitive to heat and can be inactivated at 56℃ for 30 minutes. It can be inactivated with 50% ethanol or ether, 0.2% sodium hypochlorite, 0. 1% household bleaching powder, 0.3% hydrogen peroxide and 0.5% lysol for 5 minutes, but it is not sensitive to ultraviolet rays.
It can survive for more than 15 days in a suitable liquid environment at room temperature.
[Edit this paragraph] 14. Hiv hiding place
For a long time, in clinical treatment, the medical community found that all HIV carriers who received intensive treatment reappeared in their bodies shortly after stopping treatment. It is inferred that there is not only a hiding place for HIV in infected people, but also the immune system of the body is difficult to effectively control it.
In order to solve this problem, French scientists have carried out a lot of experiments. The results show that intestinal lymph nodes provide an excellent protective barrier for HIV. Not only can the virus in HIV-positive people not be completely eliminated, but some HIV-infected people whose blood tests are still negative after 10 years also hide HIV in their intestinal lymph nodes.
After further research, scientists found that T-CD8 lymphocytes (cytotoxic T lymphocytes) in intestinal lymph nodes have poor activity, and such killer lymphocytes in other tissues can usually destroy infected cells and control viruses, but such lymphocytes in intestinal lymph nodes lack this ability, which leads to HIV hiding in them and gradually spreading to other organs, making the disease worse.
Subsequently, the researchers confirmed that it was TGF-β that caused the dysfunction of T-CD8 lymphocytes in intestinal lymph nodes, which inhibited the activity of T-CD8 lymphocytes and led to their premature aging.
French scientists said that their research provided new ideas for completely defeating AIDS, such as inhibiting TGF-β cytokines, repairing damaged T-CD8 lymphocytes and strengthening the treatment of intestinal lymph nodes. This will also be their next major task.
[Edit this paragraph] 15. Development of AIDS vaccine
According to Science magazine, at the end of 2007, scientists in the field of AIDS vaccine research can only enter the new year with a heavy heart. In mid-September, Merck announced that its mid-term clinical trial of AIDS vaccine, which lasted for 10 years, failed. At the end of September, the National Institutes of Health (NIH) decided at the last minute to stop an AIDS vaccine trial costing $65.438+300 billion. Aids vaccine research has been hit hard.
According to the latest issue of Science magazine, the vaccine was developed by NIH researchers, and the reason why NIH stopped the trial was that the trial was similar to Merck's vaccine clinical trial, which might increase the risk of HIV infection in some people.
65438+At the end of February, members of NIH AIDS Vaccine Research Subcommittee met at NIH headquarters in Bethesda, Maryland, to discuss the future fate of NIH vaccine. Although the meeting did not reach a final decision, members still reached an understanding: redesign a scheme to continue this AIDS vaccine trial, but try to reduce the risk of injury to the subjects.
"Everyone seems to think that our products (compared with Merck's products) are different enough for the next test." Peggy Johnston, head of the NIH AIDS program, said, "The question now is: What kind of experiment should be designed? Is this design practical? "
According to the data, there are about 40 million people infected with HIV in the world. If the current infection rate is calculated, 30 million people will be infected in the next five years. It is precisely because of the spread of AIDS around the world that the AIDS vaccine market has attracted more and more attention from pharmaceutical companies. Data analysis shows that in 2006, the global AIDS vaccine market capacity was 654.38+000 billion US dollars.
Merck spent 10 years developing an AIDS vaccine named V520. In 2004, Merck, National Institute of Allergy and Infectious Diseases and an academic institution named HIV Vaccine Alliance formed a team and began to implement a global human trial of V520 named Pace. On September 18 this year, Merck Pharmaceutical Co., Ltd. and its partner * * * announced that the clinical trial of V520 had failed, because a mid-term safety analysis of the trial showed that the vaccine could neither protect volunteers from deadly virus infection nor reduce the number of viruses in HIV-infected people.
This is a disastrous blow to the field of AIDS vaccine research, because Merck's vaccine is considered to be the most promising AIDS vaccine. Sarah alexander, a spokeswoman for the HIV vaccine trial network, said it was a sad day for the pharmaceutical industry because Merck's vaccine has been shown to stimulate the immune system.
However, the blow continues. NIH's AIDS vaccine was developed by Gary Lebel of NIH Vaccine Research Center. Like Merck's vaccine, both vaccines use cold virus as a carrier to deliver HIV gene to subjects. Adenovirus type 5 (Ad5) is a very popular cold virus with more than 50 subtypes, which changes rapidly. In some areas, 1/3 people may be infected with this virus, and in some places, even all people are infected.
In the trial of Merck vaccine, subjects with high Ad5 antibody level are more likely to be infected with HIV after being vaccinated with AIDS vaccine. Researchers have not yet understood the mechanism of this process, and it is not clear whether the new findings are statistically important. However, just in case, the NIH Subcommittee on AIDS Vaccine requested that people with Ad5 antibodies be excluded from the trial of AIDS Vaccine Research Center.
Scott Hammer of Columbia University is the head of the experimental project of AIDS vaccine in NIH Vaccine Research Center. He originally planned to conduct this experiment in the United States and Africa, with more than 8,500 subjects. Now, a member of Hammer's team explained that they think it's safe to conduct experiments with 2,000 ~ 3,300 subjects only in the United States and Africa, and the subjects must be Ad5 antibody negative, and the subjects will include heterosexuals and gay men.
Some members of the NIH AIDS Vaccine Research Subcommittee asked whether the trial could be focused on a narrower scope, such as gay men in the United States. Committee member Jeffrey Liverson, a vaccine expert at the National Institutes of Health, warned that Merck's research results were causing confusion, in part because the vaccine was tested in so many different people and regions. "I'm really worried ... whether this shows that we can do this research well."
David Watkins is an expert in primate research at the University of Wisconsin. He is totally opposed to such an experiment, because even if safety factors are not considered, the experiment on monkeys has shown that the experiment of NIH Vaccine Research Center will fail. He told Science magazine: "I don't understand why they still do it. Science seems to be really ignored. " Anthony Fisher, director of the American Institute of Allergy and Infectious Diseases, believes that this field is not "luxury" enough, and it will take 10 years until the data of monkey research is proved to be effective. But Fisher didn't talk about his views at the group meeting. He explained, "I'm going back to make the final decision. I don't want to draw a conclusion before anyone. "
According to the article in Science magazine, in June 5438+October 2008 10, the team of Columbia University will report the redesigned scheme to the NIH Subcommittee, and Fisher will announce the fate of this AIDS vaccine in the NIH Vaccine Research Center at that time.
How long will China have to wait for the AIDS vaccine?
In 2000, at the China Academy of Sciences 1 1 Academician Conference, Ceng Yi, an academician of China Academy of Sciences, reported that there would be no effective AIDS vaccine in the next 10 years due to the rapid mutation of the virus.
In 2006, at the13rd academic conference of China Academy of Sciences, Academician Ceng Yi once again reported on "AIDS prevention and treatment". How long will the AIDS vaccine have to wait? Academician Ceng Yi didn't give an answer, so it is difficult for any scientist to give an answer.
Human beings have been studying AIDS vaccine for more than 20 years, and now more than 120 kinds of AIDS vaccines have been tested internationally, including recombinant virus vector vaccine, DNA vaccine, protein/polypeptide vaccine and the combined application of different vaccines. Both HIV antibody vaccine and cellular immune vaccine are still in the early stage, and the developed vaccine is difficult to overcome the challenges brought by HIV in theory. Because HIV type includes at least 9 subtypes and many recombinant types (the main epidemic strain in China is B'/C recombinant type). Moreover, the virus can constantly escape the recognition and control of the immune system through genetic variation. Developing an effective AIDS vaccine has become one of the most important challenges facing mankind.
Since the 20th century, governments and international organizations have increased their investment in AIDS vaccine research, forming a good trend of global cooperation in tackling key problems. In recent years, many large pharmaceutical and vaccine companies have joined or increased their investment in AIDS vaccine research and development.
Few developing China countries have vaccine research experience, production conditions, evaluation team and management system, and international organizations generally consider China as one of the most potential partners. The first DNA and Ankana virus AIDS vaccine developed by Changchun Encyclopedia Biological Company and Hopkins University in the United States officially started the first phase of clinical trials in March 2005. The vaccine follows the mature foreign technical platform, takes DNA and non-replicating recombinant Ankana virus as carriers, and inserts the immunogen gene from CRF 08-BC, a popular strain in China, for joint immunization. The research has basically ended, marking the beginning of clinical trials of T cell vaccine in China.
In addition, China has made some progress in preclinical research of replicated and non-replicated Tiantan strain vaccinia, adenovirus vector vaccine, adenovirus-associated virus vector vaccine, Sendai virus vector vaccine, polypeptide epitope vaccine, protein vaccine and other AIDS vaccines.
Academician Ceng Yi said that although China has made some achievements in AIDS vaccine research, its international influence is limited as a whole, and none of the tested vaccines have independent intellectual property rights in China. The reasons for this situation include serious shortage of upstream R&D investment, insufficient research and innovation, lack of cooperation among teams, and disconnection between upstream and downstream vaccine research and development.
[Edit this paragraph] XVI. HIV antibody
HIV only attacks specific cells. Different cell surfaces have different protein. These protein are called "receptors", which are symbols of cell identity, just like soldiers' armor of different colors and styles. The main channels through which HIV enters immune cells and destroys human immune system are two receptors, namely CD4 and CCR5. CCR5-△32 mutation is a slight mutation in the gene encoding CCR5 receptor -32 base pairs are lost. The result is a small protein, which is not located on the surface of immune cells. In this way, most HIV strains lose their way and cannot infect cells.
Generally speaking, there are two copies of each gene in the human body. With CCR5-△32 mutant copy, people's resistance to HIV will be enhanced, and even if they are infected, the onset process will be slower than that of ordinary people. If you have two mutant copies, you are basically immune to HIV (not completely immune, two mutant copies still die of AIDS, which is rare but does exist, and some HIV strains may not need CCR5 as a channel).
The drug resistance of this mutation to HIV and ancient plague prompted scientists to investigate its frequency in different populations. The results show that this variation does not exist in African aborigines, East Asia and India, but only in the descendants of Europeans living in America and European immigrants. In other words, it is unique to Europeans. In different parts of Europe, the frequency of its occurrence is different, among which Northern Europe is as high as 14%, while the Mediterranean coast is only 2%. On average, about 10% of Europeans have one mutant copy, and 1% has two copies.
As soon as CCR5-△32 was discovered, pharmaceutical companies tried to simulate its function to make new anti-AIDS vaccines or drugs. Many people who have two copies of the mutation live healthily, which seems to show that the mutation has no harmful effects, which is particularly beneficial. However, where did it come from? This mutation only exists widely among Europeans. The reasonable explanation for this is that in historical Europe, people with this mutation have a greater chance to survive and keep their offspring. It happened by accident and existed only in a few people at first, but a violent event produced a strong "selection pressure", which increased the frequency of this mutation with certain survival advantages in the crowd.
This mutation can enhance human resistance to HIV, but it is estimated that it has a history of hundreds or even thousands of years. So what diseases in history are enough to produce such pressure? Influenza, measles, scarlet fever, typhoid fever, cholera ... Many infectious diseases have hit Europe, but the mortality and morbidity are high enough. At present, there are only two candidates: the Black Death and smallpox.
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