HIV Vaccine May Be One Step Closer with Johns Hopkins Study
Scientists have been pursuing a HIV vaccine for years, but no one has been successful until now. A research team at Johns Hopkins Medicine has replicated the cellular environment in a laboratory for creating an effective HIV vaccine. The team was able to identify which epitopes are “immunodominant”, meaning they elicit the strongest immune system response to the virus, which may spell the end for HIV-infected patients.
Identification of Immunodominant Epitopes: A Game-Changer in the COVID-19 and HIV Pandemic?
The study led by Johns Hopkins Medicine on the possibility of finding an effective HIV vaccine has raised optimism among scientists and patients alike. Due to the coronavirus pandemic, developing a vaccine against COVID-19 took a higher priority. Despite this, researchers at Johns Hopkins Medicine worked tirelessly to zero in on the immunodominant epitopes of HIV that the body recognizes and produces memory CD4+ T cells for. According to study lead author Srona Sengupta, there are more than 38 million people worldwide living with HIV and another 1 million new cases are diagnosed every year. The problem with previous methods of preparing an HIV vaccine was the lack of a complete understanding of how the immune system responds to viral pathogens. Now, the researchers were able to pinpoint the immunodominant epitopes, which is a critical step in preparing a vaccine that will elicit a meaningful antibody response in people living with the virus.
However, the consequences of this study go beyond the eradication of HIV. The COVID-19 pandemic has exposed the weaknesses of health care systems around the globe. Science and research have become more important than ever to combat the pandemic, and identifying immunodominant epitopes is vital for developing a COVID-19 vaccine. The study reveals how the team discovered new epitopes that had been missed by traditional analytics methods. As such, this could help change how scientists develop vaccines for other viral pathogens.
Understanding the Antigen Cell Process
The study conducted by the Johns Hopkins Medicine research team utilized in-vitro techniques to create a laboratory environment for mimicking the cellular environment by specialized immune cells called antigen-presenting cells (APCs). Antigens are foreign substances that can cause an immune system response, such as a virus like HIV. APCs break down HIV-derived proteins and make them visible to other immune cells known as CD4+ T lymphocytes or helper T cells. The study’s author, Scheherazade Sadegh-Nasseri, notes that in traditional vaccine development quests, synthetic peptides were used, which was an unreliable and unpredictable detection process. The researchers found that their process could identify immunodominant epitopes responsible for eliciting strong antibody responses.
Utilizing the Full-Length Natural Protein System
The in-vitro testing conducted by the Johns Hopkins team helps to paint a complete picture of the HIV proteome and reveals the epitopes that generated memory CD4+ T cells. The research team discovered that their full-length natural protein system was capable of identifying immunodominance which previous processes failed to do. The full-length natural protein system proved important due to the ability to take into account cellular environmental factors that impact the immune response, which previous testing methods did not adequately cover. The researchers were able to identify how sugar clusters modify epitopes, which can lead to new advancements in vaccine development.
Conclusion
The study conducted by Johns Hopkins Medicine has been a game-changer in HIV vaccine development and potentially more. For decades, scientists have unsuccessfully pursued a HIV vaccine, but now there is renewed optimism in the field. The process of identifying immunodominant epitopes can lead to more effective vaccine development, including for global health issues such as COVID-19. Understanding the antigen cell process and utilizing the full-length natural protein system can help prevent false positives and provide a comprehensive portrayal of the immune response.
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Since it was identified in 1984 as the cause of Acquired Immune Deficiency Syndrome (AIDS), the human immunodeficiency virus (HIV) has infected more than 80 million people and has been responsible for some 40 million deaths worldwide. according to the World Health Organization (WHO). ). Currently, the WHO reports that more than 38 million people worldwide are living with the retrovirus and another 1 million new cases are diagnosed each year. Although antiretroviral therapy helps keep HIV under control, patients must continue to take their medications to prevent the development of AIDS.
Scientists have spent years trying to develop an effective HIV vaccine, but none have been successful. According to the findings of a recently published study, a research team led by Johns Hopkins Medicine may have brought science one step closer to that goal.
His work first appeared online on April 14, 2023, in the Journal of Experimental Medicineand will be formally published in the July 3, 2023 issue.
Using a laboratory technique created at Johns Hopkins Medicine in 2010, the study researchers replicated the cellular environment in which specialized immune cells called antigen-presenting cells (APCs) break down HIV-derived proteins and make them visible (“presented”). to the immune system. first line of defense, cells known as CD4+ T lymphocytes or helper T cells.
“Our simple method, called reductionist cell-free antigen processing, reproduces in a test tube the complex events that occur in the human immune system in response to antigens, foreign invaders in the body, such as viruses such as HIV,” says the author. study principal. Scheherazade Sadegh-Nasseri, Ph.D., professor of pathology at the Johns Hopkins University School of Medicine. “When APCs chew proteins of an antigen and present the fragments, known as antigenic epitopes, on their surface, the epitopes become visible to helper T cells and initiate an immune response.”
“If we can identify which epitopes are ‘immunodominant’, the ones that elicit the strongest immune system response to the virus, then we may have the essential ingredients for the long-sought recipe for making an effective HIV vaccine,” explains Sadegh. -Nasseri.
Epitopes that are immunodominant have structures that fit uniquely like a lock and key with the cell surface proteins on APCs known as major histocompatibility molecules, or MHCs.
“If you think of an HIV epitope as a hot dog and the MHC as a bun, the ‘food’ is what is presented to the CD4+ T cells,” says the study’s lead author, Srona Sengupta, MD/Ph.D. . candidate in immunology at the Johns Hopkins University School of Medicine. “T cells that can recognize the HIV epitope-MHC complex as foreign become activated and send signals to B cells, a different type of immune cell that produces antibodies, in this case, specific for HIV. The antibodies bind to the viruses and destroy already infected cells or prevent HIV from entering the uninfected, the key functions of an effective vaccine.”
Sadegh-Nasseri says that previous efforts to map and identify the desired immunodominant epitopes have proven unreliable.
“Traditional methods use a ‘brute force’ system in which synthetic peptides representing portions of actual HIV proteins are tested in the hope that some will stimulate an immune response and direct researchers to the epitopes necessary for the development of vaccines,” says Sadegh-Nasseri. “Not only is this strategy unpredictable, but the method does not allow for real-world chemical and molecular interactions that can affect how epitopes are produced and function.”
This, he explains, is one of the main reasons why an effective HIV vaccine remains elusive.
“Our cell-free antigen processing system,” says Sadegh-Nasseri, “replicates how epitopes in the APC cellular environment are actually processed and presented, including influencing factors that may come into play.”
“This allowed us to study almost the entire HIV proteome [all of the proteins produced by the virus] and clearly identify the epitopes that are selected for presentation to CD4+ T cells by a chaperone protein called HLA-DM,” says Sengupta. “That’s important because we know that HIV epitopes processed and edited by HLA-DM are immunodominant”.
Sengupta adds that 35 epitopes identified in the recent studies were previously unknown.
The researchers say their analysis using the cell-free antigen-processing system revealed three important findings: (1) the identified epitopes are generated in humans who are HIV-positive and lead to the development of memory CD4+ T cells (the immune cells that remember an antigen for future encounters); (2) the processing system can be very useful in predicting which parts of HIV protein antigens can produce immunodominant epitopes that can be included in new vaccines; and (3) the use of the full-length natural protein system ensures that the impacts of any cellular environmental influences (such as those that cause modifications of viral epitopes after they have been produced by infected host cells) are taken into account.
Current analytics technologies lack such capabilities, say Sadegh-Nasseri and Sengupta.
“Interestingly, we identified several epitopes that were modified by sugar clusters, a potentially important finding for vaccine developers, but one that traditional analysis would have missed,” says Sengupta.
Sadegh-Nasseri and Sengupta say their team will continue to refine the immunodominant epitope identification system and use data from future assays to improve the ability of vaccine developers to design robust and effective protective measures not only against HIV, but also against SARS-CoV-2 (the virus that causes COVID-19) and other viral pathogens.
Along with Sadegh-Nasseri and Sengupta, members of the Johns Hopkins Medicine and Johns Hopkins University study team are Nathan Board, Tatiana Boronina, Robert Cole, Madison Reed, Kevin Shenderov, co-lead author Robert Siliciano, Janet Siliciano, Andrew Timmons , Robin Welsh, Weiming Yang, and Josephine Zhang. The team also includes Steven Deeks and Rebecca Hoh from the University of California, San Francisco, and Aeryon Kim from Amgen Inc.
https://www.sciencedaily.com/releases/2023/05/230530174312.htm
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