Mapping Childhood Immunity: Dr. Joshua Gray Aspires to Draft a New Blueprint for Improving Pediatric Vaccines
Infants are not simply miniature adults when it comes to immune defense. Nor are they entirely defenseless, another common misconception. “Infant and adult immune responses are fundamentally different, not just in maturity level, but in how they're programmed,” says Dr. Joshua Gray, winner of the 2026 Michelson Prizes: Next Generation Grants.
Gray has discovered entirely novel immune mechanisms that protect children from pathogens in early life, which traditionally has been a vast unknown due to the difficulty in procuring and studying human tissues from infants and children. To unlock this black box, Gray has helped assemble one of the largest pediatric tissue resources in the United States through a collaboration with national organ procurement organizations across the country. Probing this rare resource with next-generation tools including spatial transcriptomics, functional profiling and computational modeling, he is creating the first integrated map of mucosal immunity in children. This groundbreaking advance in the field has already revealed many unexpected aspects of immunity that will open doors no one could access before.
“One key mechanism we've discovered is that infants have immune clusters in both their lungs and gut—at mucosal sites where they're most likely to first encounter pathogens. These clusters contain B and T cells working together to produce localized antibody responses that respond rapidly to insults at the infection site,” says Gray. These immune clusters, called Bronchus and Gut-Associated-Lymphoid Tissue (BALT & GALT), may be one of the reasons children were more protected against the SARS-CoV-2 virus. Their immune systems are designed to jump into action against novel pathogens at the first site of exposure, nipping infection in the bud-- whereas adults rely more heavily on immune memory, which was non-existent for this new virus.
Gray’s discovery shifts fundamental assumptions about human immunology, with profound implications for childhood vaccines, which are actually designed for adult immune systems because historically, we had no other choice. He will use the Michelson Prizes: Next Generation Grants funds with a bold goal: design vaccines that engage the immune system children actually have, not the one adults rely on. “The idea is to understand how these immune clusters work, so we can intentionally engage these infant-specific programs. It could result in very different vaccine regimens for children. That's the long-term goal,” says Gray.
Gray’s approach to reimagine pediatric vaccines has transformative implications for vaccine design, delivery and efficacy. By decoding how infant mucosal immunity actually operates, and intentionally engaging these mechanisms in the lung and gut, he aims to inform the design of inhaled or orally delivered vaccines that would drive protection on the front lines of pathogen exposures. The strategy also promises stronger durability—potentially eliminating the needs for repeated boosters. Many current pediatric vaccines such as RSV and influenza do not provide lasting protection precisely because they are taking aim at immune memory processes that do not exist in children. By leveraging these newly discovered immune mechanisms, Gray hopes to elicit long-term protection by engaging the processes actually responsible for generating immune memory in children. “This work has the potential to reshape how we approach vaccination and immune-based therapies at various stages of human life by uncovering how protective immunity is naturally built during infancy,” he says.
The impact of Gray’s work also extends beyond childhood and vaccinology. Structures resembling BALT can appear later in life in various disease contexts. In autoimmune diseases, they can drive harmful inflammation. Meanwhile, in cancers, they can improve immunotherapy responses and outcomes. Gray’s efforts to understand how these structures operate in childhood could inform novel immunotherapy strategies targeting these mechanisms to treat adult diseases.
This project represents exactly the kind of bold, high-risk, high-reward science the Michelson Prizes: Next Generation Grants seeks to propel. “Proposing a whole new approach to how we should vaccinate infants seems quite high-risk when we've spent the past 100 years developing vaccines based on how adults respond. But I also think it's high reward,” says Gray, whose project aligns perfectly with the Michelson Medical Foundation’s mission to support ambitious and disruptive concepts with the potential to advance human immunology, immunotherapy and vaccine discovery.
Gray is driven by intrigue and impact. The appeal of diving into the infinitely explorable complexities of the human immune system is what drew him to the field originally, and what makes research fun for him to this day. On the brink of starting his independent research career, he has his sights set ultimately on the translational human impact of his work, driven by the potential to transform the health of future generations. “I believe that understanding how the immune system protects children during the most vulnerable stages of life is a worthy problem to dedicate my career to. Vaccines have transformed human health, yet there is still much to learn about how to make them work optimally in early life. Contributing clear, rigorous knowledge that improves our understanding of immunity and supports better vaccines for children is what keeps me going.”
