Strong initial antigenic stimulation could pave the way for sustained HIV immunity without the need for consecutive vaccinations
Researchers recently published a study looking at vaccines that looked at how HIV treatment and immune signatures affect the body’s ability to fight the virus through the production of antibodies. These antibodies, called broadly neutralizing antibodies, are important because they can target and neutralize different strains of HIV. This is critical for developing an effective HIV vaccine, as these antibodies can help create long-lasting protection against the virus. The research was led by Dr. Victor Sanchez-Merino and Dr. Eloisa Yuste at the National Center of Microbiology (ISCIII) in Madrid, Spain. These findings are expected to play a role in advancing HIV-1 vaccine strategies.
The scientists worked with more than 200 participants, including adults and children under the age of 15, all of whom had undetectable HIV-1 levels in their blood due to ongoing HIV treatment. This study aimed to identify the potential for aviromic children and adults to mount a broadly neutralizing response to HIV-1, while emphasizing the importance of antiretroviral timing and immune signatures in this process. As Dr. Sanchez-Merino explains: “What we found is that the breadth of neutralization in individuals with AVI is associated with the timing of treatment initiation and the CD4+/CD8+ ratio in children and adults with HIV-1 CD4+/CD8+ ratio”.
The study’s results suggest that adults are much better than children at producing broadly neutralizing antibodies. Almost half of adults can neutralize several different strains of HIV, while only a handful of children show the same ability. Researchers believe this is because adults are often treated later than children, giving their immune systems more time to be exposed to the virus. In contrast, children often begin treatment after infection, limiting their immune systems’ exposure to HIV and reducing their ability to develop these protective antibodies.
Both adults and children showed two important relationships between the ratio of immune cells and the strength of their antibody responses. When the balance of CD4-positive versus CD8-positive cells was lower, participants were more likely to have stronger neutralizing responses. This suggests that a higher proportion of CD8-positive cells relative to CD4-positive cells may help the body fight multiple strains of HIV more effectively. The researchers also noted that other factors, such as the total length of time someone has been on HIV treatment or the time since first infection, did not appear to affect their ability to produce these antibodies. This highlights the importance of early immune responses in controlling HIV.
The findings also suggest that children who start HIV treatment within a few months of birth have little ability to neutralize the virus. This suggests that starting treatment too early may prevent the immune system from developing the ability to recognize and fight HIV in the future. “We found that children who are infected at birth and start treatment often lose specific antibodies that help their immune systems fight HIV,” said Dr. Yuste. “These results highlight the importance of controlling the virus early and allowing the immune system to be exposed enough to mount a strong defense.” The fragile equilibrium provides important clues for improving future HIV treatment and vaccine approaches.
The team recommended that more research should be conducted to understand how long-term exposure to the virus before treatment affects the development of these broadly neutralizing antibodies. In particular, the study highlights the importance of learning more about how children’s immune systems differ from those of adults, which could lead to better HIV treatment and prevention methods. As Dr. Sanchez-Merino points out, “Our work shows that these important antibody responses can develop even in the absence of sustained exposure to the virus, as long as the immune system is initially exposed to large amounts of the virus.”
These findings could have a major impact on the development of HIV vaccines. The ability to generate long-lasting antibodies, even without continuous exposure to the virus, may lead to better designed vaccines. Future strategies may require careful consideration of when and how much virus should be introduced into the immune system to create the strongest, most durable defense, especially in younger people.
Overall, this study demonstrates that ensuring adequate antigenic stimulation prior to initiating ART improves the ability to generate a durable broadly neutralizing response. This suggests that these responses can be induced without the need for sequential vaccines as long as the initial antigenic stimulation is robust and sustained. These findings have important implications for the development of effective vaccination strategies against HIV.
Journal reference
Sanchez-Merino, V., Martin-Serrano, M., Beltran, M., Lazaro-Martin, B., Cervantes, E., Oltra, M. wait. (2024). “Correlation of neutralization with CD4+/CD8+ ratio in children and adults with Ahlweis disease.” Vaccine, 12(8). doi: https://doi.org/10.3390/vaccines12010008
About the author
Víctor Sánchez Merino: Graduated with a Bachelor’s degree in Pharmacy and a PhD from the Integrated University of Madrid, specializing in Virology and Molecular Biology. His research focuses on HIV and EBV. His PhD thesis describes the evolution of HIV-1 and the restoration of mutant HIV-1 reverse transcriptase function. He completed a postdoctoral residency at Harvard University studying novel viral interactions (2001-2003). At the University of Massachusetts, he explored CD8+ T cell responses in vertical transmission of HIV (2003-2008). In Spain, at the Hospital Clínic-Idibaps (Barcelona; 2008-2017) and the Carlos III Health Institute (Madrid; 2017-Present), he led research on HIV-1 neutralizing antibodies and Design of preventive vaccines. He is currently co-lead with Dr. Eloísa Yuste Herranz of the National Center of Microbiology (Instituto Carlos III Health, Madrid, Spain). Furthermore, he is professor and principal researcher at Alfonso X El Sabio University (Madrid).
Eloísa Yuste Herranz: Graduated from the Integrated University of Madrid with a Bachelor’s degree in Biological Sciences and a PhD. She completed her first postdoc (1998-2001) at the Severo Ochoa Center for Molecular Biology (Madrid). In 2001, she completed her second postdoctoral residency at Harvard Medical School in the United States and was promoted to associate researcher in 2005. In 2008, she joined the August Pi Sunyer Biomedical Research Institute (BARCELONA) (Barcelona) as a Ramón Y Cajal y Cajal y Cajal y researcher. In 2011, she was promoted to i3 researcher at the same institution. In 2016, she joined the National Center of Microbiology of the Carlos III Health Institute (Madrid) as a Distinguished Researcher. In 2018, she was promoted to senior scientist at the same institution. Her research focuses on the study of humoral immunity to HIV-1 and the development of prophylactic HIV-1 vaccine prototypes. She currently co-leads the study with Dr. Víctor Sánchez Merino of the National Center of Microbiology (Instituto Carlos III Health, Madrid, Spain).
