Emerging viral diseases from a vaccinology perspective: preparing for the next pandemic

Abstract

Emerging infectious diseases will continue to threaten public health and are sustained by global commerce, travel and disruption of ecological systems. Most pandemic threats are caused by viruses from either zoonotic sources or vector-borne sources. Developing better ways to anticipate and manage the ongoing microbial challenge will be critical for achieving the United Nations Sustainable Development Goals and, conversely, each such goal will affect the ability to control infectious diseases. Here we discuss how technology can be applied effectively to better prepare for and respond to new viral diseases with a focus on new paradigms for vaccine development.

Fig. 1. Emerging technologies support a new paradigm for vaccine development.

Several new or improved technologies over the past 10 years have provided the tools needed for rational vaccine design. They have also created opportunities for more-rapid vaccine development. Structure-guided antigen design is a central feature of this new paradigm. Atomic-level detail of antigenic surfaces, the ability to identify monoclonal antibodies via the cloning of immunoglobulin-encoding genes from specifically sorted B cells, and high-throughput sequencing technology have provided the basis for selecting antigen targets for vaccine-induced immune responses to initiate the design cycle. CRISPR-Cas9-like targeted gene editing has made it possible for animal models to be established on the basis of knowledge of receptor requirements for viral entry and restriction factors that might be species specific. Analysis of immune responses by flow cytometry to define the phenotype of individual cells on the basis of protein- or gene-expression patterns can provide information on repertoire and temporal patterns of the immune response for bridging endpoints to human infection or vaccination. Knowledge of the structure, function and epitope locations for class I fusion proteins across families of viruses provides a basis for selecting these as vaccine targets and for initial antigen designs. Having functional monoclonal antibodies to test antigens for authentic binding surfaces can guide the protein engineering needed to make immunogens. Recognition by B cells is facilitated when antigens are displayed in ordered arrays, and self-assembling nanoparticles provide a vehicle for presenting vaccine antigens in this way. The advent of gene-based expression of antigens from nucleic acids or vectors, advances in adjuvant formulations, and microneedle patches (bottom right) or  needle-free or alternative inoculation devices can also contribute to the shortening of timelines and improved efficacy of new vaccines. Ig, immunoglobulin; κ and λ, components of the immunoglobulin light chain (IgL); TCR, T cell antigen receptor; BCR, B cell antigen receptor; ± DS, with or without disulfide bonds; SP, signal peptide; ± RBD, with or without a receptor-binding domain; FP, fusion peptide (upward arrowheads indicate upstream cleavage sites); HR1 or HR2, heptad repeat 1 or 2; TM, transmembrane region; CT, carboxyl terminus. Credit: Debbie Maizels/Springer Nature.

Fig. 2. Synthetic vaccinology.

The ability to quickly synthesize nucleic acids has made it possible to rapidly translate sequences identified in the field into reagents needed for the initiation of a vaccine-development process. This can be communicated electronically without the sharing of physical samples, which removes the complexities of shipping and handling biological samples. This is also a practical justification for having surveillance and sequencing ability broadly distributed throughout the world. Credit: Debbie Maizels/Springer Nature.