Innovations in structure-based antigen design and immune monitoring for next generation vaccines

The recent explosion of atomic-level structures of glycoproteins that comprise the surface antigens of human enveloped viruses, such as RSV, influenza, and HIV, provide tremendous opportunities for rational, structure-based vaccine design. Several concepts in structure-based vaccine design have been put into practice and are are well along preclinical and clinical implementation. Testing of these designed immunogens will provide key insights into the ability to induce the desired immune responses, namely neutralizing antibodies. Many of these immunogens in human clinical trials represent only the first wave of designs and will likely require continued tweaking and elaboration to achieve the ultimate goal of enhanced breadth and potency. Considerable effort is now being invested in germline targeting, epitope focusing, and improved immune presentation such as multivalent nanoparticle incorporation. This review highlights some of the recent advances in these areas as we prepare for the next generation of immunogens for subsequent rounds of iterative vaccine development.