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HIV / AIDS Vaccines: Why do I have several COVID-19 vaccines after a few months, but not one after 37 years?
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 Smallpox has been eradicated from the surface of the globe as a result of a highly effective global vaccination campaign. In the United States, with the development and use of effective vaccines against poliovirus, paralytic polio is no longer a problem. Today, the rapid deployment of effective vaccines against COVID-19 has saved millions of lives. Still, 37 years have passed since HIV was discovered as the cause of AIDS, and there is no vaccine. This section describes the challenges facing the development of effective vaccines against HIV / AIDS. I am a professor of pathology at the University of Miami Miller School of Medicine. In my laboratory, a monkey virus called SIV or a monkey immunodeficiency virus is said to have been discovered. 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. Dr. Anthony Fauci talks about the difficulty of finding an HIV / AIDS vaccine in 2017. Efforts to develop the HIV vaccine were completed in a short period of time. Vaccines are undoubtedly the most powerful weapon in society for medically important viral diseases. When the new disease AIDS broke out in the early 1980s and the virus that caused it was discovered in 1983-84, it was not surprising that the research community could develop the vaccine. At a now-famous press conference that announced HIV as the cause of AIDS in 1984, then US Secretary of Health and Social Welfare Margaret Heckler predicted that the vaccine would be available within two 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. To date, there have been five large-scale Phase 3 vaccine efficacy trials for HIV, each costing more than US $ 100 million. The first three of these made very compelling mistakes. There 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 trials, the STEP trial, the frequency of infection in vaccinated individuals was statistically significantly higher. The fourth, the controversial Thai RV144 trial, initially reported that vaccinated individuals had little success in protecting against the acquisition of HIV infection. 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 trial was discontinued early due to no benefit. There is no protection against acquisitions. There is no decrease in viral load. painful. What is the HIV complexity issue? 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 outweighs the variability of the global sequence of influenza viruses 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 viruses, such as coronavirus and herpesvirus, 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 exposed glycoproteins are 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. [Understand new developments in science, health and technology, each week. Subscribe to The Conversation’s science newsletter.] So should we researchers give up? No, it shouldn’t. One approach that researchers are trying in animal models in some laboratories is to use herpesviruses as vectors to deliver AIDS virus proteins. The herpesvirus family belongs to the “persistent” category. When you get infected with the herpes virus, you will be 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, while some rare individuals have strong neutralization against a wide range of HIV isolates. Create an active antibody. 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, an adeno-associated virus. When the vector is administered to muscle, muscle cells become a factory that continuously produces strong, widespread neutralizing antibodies. Researchers recently recorded six and a half years of continuous production of monkeys. ** VL: I think this is this treatise. Quote from the abstract “Here we report that Monkey 84-05 succeeded in maintaining 240-350 μg / ml anti-SIV antibody 5L7 for more than 6 years”: https: //dx.doi.org/ 10.3389% 2Ffimmu.2020.00449) We are making progress. This article has been republished by The Conversation, a non-profit news site aimed at sharing ideas from academic experts. It was written by Ronald C. Desrosiers of the University of Miami. Read more: Does my child need to be vaccinated with COVID-19? Seven Questions Answered by Pediatric Infectious Diseases Experts How HIV became a treatable chronic disease Ronald C. Desrosiers is funded by the National Institutes of Health.