Atomic-level structural information and advances in synthetic biology and nanotechnology have created new opportunities for generating vaccines in a way that has not been possible using traditional methods. These novel approaches to recombinant vaccine design are opening doors to the development of vaccines against challenging targets. In this chapter, we discuss the exceptional humoral immunogenicity of virus-like particles (VLPs) and related nanoparticles and their application to vaccine development. The emergence of this new category of vaccine platforms is based on recent insights from multiple fields of study, including immunology, virology, nanotechnology, structural biology, synthetic biology, and bioengineering. The multidisciplinary work on VLP and nanoparticle immunogens is already yielding dividends for public health, but is also likely to result in safer, more potent and broadly protective vaccines against a wide variety of human and animal pathogens, as well as target host proteins of interest.
Whole-genome sequencing of bacteria and advances in bioinformatics have revolutionized the vaccinology field, leading to the identification of potential vaccine candidates without the need for cultivating the pathogen. This approach, termed "reverse vaccinology", reduces the time and cost required for the identification of candidate vaccines and provides new solutions for those diseases for which conventional approaches have failed. The first example of the potential of reverse vaccinology has been the identification of novel antigens of meningococcus B as potential candidates for a novel and effective vaccine. The same approach has been successfully applied to other important human pathogens, demonstrating the feasibility to develop vaccines against any infectious disease. This review focuses on some recent advances in the identification of vaccine candidates by mining the genomic sequences of pathogenic bacteria.
Genetic diversity has underpinned the survival and expansion of human populations against a long history of varied microbial challenges, but may limit the universal immunogenicity of current vaccines against particular pathogens. Reduced or non-responsiveness is a barrier to total pathogen eradication for established vaccines, and remains the key impediment to licensure for a number of investigational vaccines. Genetic association studies have identified some determinants of vaccine immunogenicity, many of which act at single molecular interactions within complex pathways and networks. To date these immune modifying polymorphisms explain only a fraction of the known variation in vaccine responses and the most striking aspect of individualized immunity, immunodominance, remains a central issue in new vaccine design. Vaccine personalization is likely to require not only a systems biology approach to understand broad vaccine response phenotypes, but also an understanding that the specificity of antigen recognition unique to every vaccinee and restricted by their human leukocyte antigen (HLA) genotype, determines the unique CD4 and CD8 T cell and natural killer (NK) cell repertoires available for vaccine induction. This chapter discusses the role of HLA and non-HLA loci, and pathogen-specific adaptations relevant to vaccines and explores ways these could be exploited in vaccine design and personalization.
As new vaccines are introduced and existing vaccines are targeted for new populations, it is important to understand the unique aspects of "special populations." The goal of this chapter is to identify these special populations, discuss their burden of vaccine preventable disease and evaluate their impact on vaccine policy. This chapter will also present the specific challenges and concerns with respect to vaccine immunogenicity, efficacy, and safety within these populations. It will also propose new areas of investigation into the optimization of these immunization parameters. The special populations to be considered include infants, pregnant women, and immunocompromised individuals and older adults. Each of these groups will be discussed separately in the context of representative vaccines.
This chapter considers the statistical evaluation of vaccine efficacy based on randomized, controlled, preventive vaccine efficacy trials. After defining concepts and target parameters for measuring vaccine efficacy, the remainder of the chapter focuses on studying unconditional vaccine efficacy to reduce susceptibility to pathogen infection or disease, measured cumulatively over time. A unified approach to studying how this type of vaccine efficacy depends on the following four factors is presented: baseline participant characteristics, biomarkers measuring immune responses to vaccination, genotypic and phenotypic characteristics of exposing pathogens, and time since vaccination. Statistical issues and design and analysis techniques for learning about such correlates of vaccine efficacy are discussed, including on the use of high-dimensional assays such as whole genome transcriptomic and mass cytometry assays.
