Non-neutralizing antibodies
Antibodies that recognize viruses but do not block virus infection in the lab are known as ‘non-neutralizing antibodies’. These have been historically overlooked in favor of the classical ‘neutralizing antibodies’. However, it is now appreciated they can act through a range of protective mechanisms, and our lab is uncovering new ways in which they contribute to antiviral immunity. Recently we uncovered a novel pathway by which non-neutralizing antibodies boost antigen presentation by intracellular activity, leading to stronger activation of virus-killing cytotoxic T cells. This discovery highlights a new kind of synergy between antibody- and T cell–mediated immunity. We are now investigating the mechanisms behind this process, with the long-term goal of harnessing it to improve vaccine design. We are also investigating how non-neutralizing antibodies function across different stages of life, recognizing that assumptions based on adult immunity may not always hold true in newborns or children.
Correlates of protection for rotavirus
Rotavirus is one of the leading causes of severe diarrhea in children worldwide. Thankfully there are vaccines available to limit disease caused by this virus, but exactly how these protect infants is unclear. At present the best-established predictor of whether an infant is protected from disease, the so-called ‘correlate of protection’ (CoP), is serum IgA. However, this CoP is not perfect at the individual level, and the complexity of the protective immune response still needs to be unraveled. Our lab is dissecting which rotavirus-specific antibodies are responsible for neutralizing virus both inside and outside of cells. By clarifying the true CoP, we aim to generate knowledge that will guide the next generation of rotavirus vaccines.
Maternal antibody interference
Maternal antibodies provide newborns with a critical first layer of immune protection, but they can also reduce the effectiveness of early-life vaccination. This paradox, protection versus interference, remains a major challenge in global health. Our lab is working to identify which maternal antibodies interfere with infant vaccine responses and how, using both human samples and animal models. Understanding these mechanisms will help us develop strategies to overcome interference and improve vaccine effectiveness in the youngest populations.
Maternal antibody transfer in different species
The way maternal antibodies are passed to newborns varies dramatically across species: humans transfer antibodies through the placenta, while dogs and horses rely almost entirely on antibodies in colostrum and milk. Our lab studies these species-specific differences to understand how maternal immunity is established in early life. We are using a combination of functional and biophysical antibody assays to study how transfer is mediated. This comparative approach not only informs veterinary medicine but also sheds light on fundamental principles of maternal–neonatal immune interactions that are relevant to human health.
