Global-Ig: a population-based antibody library technique to optimize the development of globally protective vaccines

As the SARS-CoV-2 pandemic has demonstrated, vaccines that provide broad global protection are needed.

However, human antibody genes are highly variable and thus, the quality of vaccine-induced responses can vary between population groups.

This variation is shaped by the long history of host/disease interactions and differences in endemic diseases between regions over time, resulting in differences in antibody allele frequencies between populations.

Therefore, information about how nave antibody repertoires representing diverse population groups recognize vaccine candidates would greatly improve the development of broadly protective vaccines.

In this Proof-of-Concept grant, we will develop a technique, Global-Ig, which allows in vitro production of large antibody libraries from a database of antibody germline gene variants representing the range of human global variation observed in the major population groups of the world, which we have assembled as part of our ongoing ERC Advanced project.

Libraries representing different population groups will be used to prospectively identify differences in B cell recognition of candidate vaccines to facilitate selection of vaccine antigens that are broadly recognized.

In cases where suboptimal binding to a vaccine antigen is detected for one or more population groups, the antigen can be modified to better accommodate population-specific alleles.

Importantly, prospective screening against population-based antibody libraries in vitro offers possibilities to identify antigens that are broadly recognized prior to advancing candidates to clinical trials, substantially reducing costs associated with clinical development and improving health equity.

Thus, the population-based Global-Ig antibody library technique described here represents an opportunity to harness information about human antibody germline gene variation gained in our ongoing ERC Advanced grant to select and tailor vaccine candidates for a global market.