This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: A vaccine's molecular structure plays a key role in determining how the immune system responds and prepares to protect the body from future exposure to a specific pathogen. To develop a vaccine that offers long-term protection from HIV, it's essential to promote a long-lasting immune response in which immune cells and antibodies prepared to combat the virus persist within the body.
This has inspired scientists to find ways to alter vaccine structure to increase the duration and persistence of the immune response. Now, in a pair of preclinical studies, each published in Science Translational Medicine on Aug. 12, 2026, scientists from Scripps Research, the University of Texas Medical Branch and IAVI found that increasing the "avidity"—or overall binding strength—of vaccine nanoparticles to specific white blood cells promotes stronger and more durable immune responses in mice. The first study examined how avidity affects the durability of the immune response, while the second study looked at how avidity influences which immune cells are most successful during that response.
By demonstrating how higher overall binding strength could improve immune performance, these findings may help researchers design the next generation of vaccines for HIV and other infectious diseases. "We're trying to dial all the knobs we can in terms of vaccine design to get the strongest possible immune responses to stop HIV," says the co-senior author of both studies, Scripps Research professor William Schief, who's also the vice president of protein design in infectious disease research at Moderna Inc. and an executive director of vaccine design at IAVI's Neutralizing Antibody Center. "Both of these papers show that nanoparticles with higher overall binding strength lead to stronger immune responses at basically every stage of the overall response.
This makes overall binding strength a promising aspect to explore to make better vaccines." Previous work led by Schief and his colleagues demonstrated the ability to produce mature, functional broadly neutralizing antibodies that block many different HIV strains from infecting cells in nonhuman primates. The researchers believed that a key to success in this prior study was the use of a nanoparticle at the last vaccination. But the study did not look at the durability of the immune response or how to optimize it.
Schief's team suggested that increasing the overall binding strength of the nanoparticles may be one way to do so. In particular, the new studies looked at how strongly a vaccine nanoparticle binds to the intended precursor B cells—white blood cells that can mature into cells that release antibodies—within the body. This overall binding strength combines two factors: the repetitiveness and the binding strength of individual B cell attachment points within a single nanoparticle.
Historically, it's been difficult to tell the relative impact of each of these features in determining the overall binding strength. Schief and his team had some tricks up their sleeves to deconstruct the specific contributions of repetitiveness and attachment-point binding strength, using carefully engineered vaccine nanoparticles. Members of Schief's lab engineered a set of six types of vaccine nanoparticles with a range of repetitiveness: The most repetitive had 60 functional attachment points, while the least had zero.
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