The personal touch: strategies toward personalized vaccines and predicting immune responses to them

Abstract

The impact of vaccines on public health and wellbeing has been profound. Smallpox has been eradicated, polio is nearing eradication, and multiple diseases have been eliminated from certain areas of the world. Unfortunately, we now face diseases such as hepatitis C, malaria or tuberculosis, as well as new and re-emerging pathogens for which we lack effective vaccines. Empirical approaches to vaccine development have been successful in the past, but may not be up to the current infectious disease challenges facing us. New, directed approaches to vaccine design, development, and testing need to be developed. Ideally these approaches will capitalize on cutting-edge technologies, advanced analytical and modeling strategies, and up-to-date knowledge of both pathogen and host. These approaches will pay particular attention to the causes of inter-individual variation in vaccine response in order to develop new vaccines tailored to the unique needs of individuals and communities within the population.

Figure 1. Vaccinomics and Predictive Vaccinology

Vaccinomics incorporates: 1) the use of omics-level technologies, from genome to proteome, to metabolome; 2) appropriate measures of innate and adaptive immune function; and 3) information regarding host genetics/genomics, host-pathogen interactions, and host microbiome. These data are integrated and analyzed at multiple levels (unsupervised, data-driven analyses, individual parameter analyses, and pathway/network/module/geneset analyses incorporating known biologic function). The analyses are followed by computational and predictive modeling strategies (Prediction Analysis for Microarrays, K-Nearest Neighbor, Classification to Nearest Centroids, Support Vector Machines, Discriminant Analysis via Mixed Integer Programming, Generalized Linear Model) that allow investigators to predict immunogenicity and/or vaccine efficacy. Results from these studies inform vaccine development and clinical trials. Results from the clinical trials lead to new products and form the foundation for the next cycle of scientific discovery.