This section describes the challenges facing the development of effective vaccines against HIV / AIDS.
I Professor of Pathology At the University of Miami Miller School of Medicine.My lab is credited for the discovery of a monkey virus called SIV, or simian immunodeficiency virus.. SIV is a closely related species of the virus that causes AIDS in humans (HIV, or human immunodeficiency virus). My research has contributed significantly to understanding the mechanisms by which HIV causes disease and to working on vaccine development.
Laboratory workers will extract DNA from the sample for further testing at the AIDS Vaccine Design and Development Laboratory in New York City on December 1, 2008. Chris Hondaros / Getty Images Beer The Conversation
Lack of efforts to develop HIV vaccine
Vaccines were arguably the most powerful weapon in society for medically important viral diseases.When AIDS, a new illness, rushed into the field in the early 1980s The virus that caused it was found It was not surprising that the research community could develop the vaccine between 1983 and 1984.
Dr. Anthony Fauci is discussing the difficulty of finding an HIV / AIDS vaccine in 2017.
Margaret Heckler, then Secretary of Health and Social Welfare, at a now-famous press conference that announced HIV as the cause of AIDS in 1984. Vaccine predicted to be available within 2 years.. Well, it’s 37 years later and there is no vaccine. The lack of HIV vaccine is in stark contrast, as the development and distribution of the COVID-19 vaccine is rapid. The problem is not government failure. The problem is not lack of spending. The difficulty lies in the HIV virus itself. In particular, this includes the remarkable diversity of HIV strains and viral anti-immunity strategies.
Have been so far Efficacy of 5 Large Phase 3 Vaccines Testing for HIV, each costing over US $ 100 million. The first three of these made very compelling failuresThere is no protection against the acquisition of HIV infection, and there is no reduction in viral load in infected people. In fact, in the third of these exams, the STEP exam, Statistically significantly higher infection frequency In vaccinated individuals.
Fourth trial, controversial Thai RV144 TrialInitially reported that the degree of successful protection against the acquisition of HIV infection in vaccinated individuals was modest. However, subsequent statistical analysis reports that the actual protection against acquisitions is less than 78%.
The fifth vaccine trial, the HVTN702 trial, was ordered to confirm and extend the results of the RV144 trial.The· HVTN702 study was discontinued Early because of waste. There is no protection against acquisitions. There is no decrease in viral load. painful.
HIV complexity
What is the problem? The evolved biological properties of HIV make the development of successful vaccines extremely difficult. What are those properties?
First and foremost, it is a relentless and continuous viral replication. When HIV steps into the door, it’s a “pitfall.” Many vaccines do not completely prevent the acquisition of infection, but they can severely limit virus replication and possible resulting illness. For a vaccine to be effective against HIV, it will need to provide an absolute sterile barrier as well as restrict viral replication.
HIV has evolved its ability to generate and tolerate many mutations in its genetic information. This results in enormous amounts of variation between strains of the virus, not only from one individual to another, but even within one individual. Let’s use the flu for comparison. Everyone knows that the influenza strains that are prevalent vary from season to season, so you need to be re-vaccinated with the influenza virus each season.Now, the variability of HIV within a single infected individual Exceeding the overall global sequence variation of influenza virus Throughout the season.
What should be included in the vaccine to cover this degree of strain variation?
HIV has also evolved its incredible ability to protect itself from antibody recognition. Envelope virus Coronaviruses, herpesviruses, etc. encode on the surface the structures that each virus uses to invade cells. This structure is called “glycoprotein <" and means that it is composed of both sugar and protein.However HIV Top Glycoprotein It’s extreme. It is the sugariest protein of all viruses in all 22 families. More than half of the weight is sugar. The virus then realized how to use these sugars as a shield to protect itself from the recognition of the antibodies that the infected host was trying to make, that is, the virus evolved by natural selection. The host cell adds these sugars and considers them self.
These properties have important consequences associated with vaccine development efforts. Antibodies made by HIV-infected persons usually have very weak neutralizing activity against the virus. In addition, these antibodies are highly strain-specific. They neutralize the strains that individuals are infected with, but not the thousands of other strains that circulate within the population. Researchers know how to elicit antibodies that neutralize one strain, but not antibodies that have the ability to protect against thousands of strains circulating in the population. This is a major issue for vaccine development efforts.
HIV is constantly evolving within an infected individual to stay one step ahead of the immune response. The host elicits a specific immune response that attacks the virus. It exerts selective pressure on the virus, and natural selection reveals mutant viral variants that are no longer recognized by the individual’s immune system. As a result, relentless viral replication occurs continuously.
So should we researchers give up? No, it shouldn’t. One approach that researchers are trying with animal models in several laboratories is Herpesvirus as a vector Provides AIDS virus protein. The herpesvirus family belongs to the “persistent” category. When you get infected with the herpes virus, you are infected for the rest of your life. And the immune response lasts not only as a memory, but in a continuous and active way. However, the success of this approach still relies on understanding how to elicit a range of immune responses that allow coverage for the highly complex HIV sequences that circulate within the population.
Another approach is to pursue protective immunity from a different angle. The majority of individuals infected with HIV produce antibodies with weak strain-specific neutralizing activity, but some rare individuals do. Antibodies with strong neutralizing activity For a wide range of HIV fractions. These antibodies are rare and very rare, but our scientists own them.
Scientists have also recently figured out ways to maintain protective levels of these antibodies for life with a single dose. For life!This delivery relies on a vector called a viral vector, Adeno-associated virus.. When the vector is administered to muscle, muscle cells become a factory that continuously produces strong, widespread neutralizing antibodies.Researchers recently documented 6 and a half years continuous production in monkeys..
We are making progress. Don’t give up.
Along Ronald C. Desrosiers, Vice Chairman of Research, University of Miami, Professor of Pathology <. This article has been republished by The Conversation under a Creative Commons license.Read Original work..
