Carbohydrate-Based Vaccines: From Concept to Clinic Downloaded from pubs.acs.org by 146.185.200.36 on 09/16/18. For personal use only.
Foreword This volume evolved from a gathering held as part of the 2017 American Chemical Society National Meeting. The conference included scientists, from academia and industry, involved in the design and development of carbohydrate-based vaccines. When members of the general public think of vaccines, they immediately focus in on “classic” viral vaccines such as measles, mumps and polio. Vaccines to prevent bacterial infections do not immediately come to mind, partly due to the lower incidence of severe bacterial disease. When the impact of bacterial infections is considered, it is usually in the context of diseases resulting from exposure to bacterial toxins. Of course, highly effective toxoid-based vaccines to prevent diseases such as diphtheria and tetanus have been available for decades. However, there are a number of bacterial infections that can present a spectrum of disease manifestations, some of which can be quite severe. This is particularly the case for infants and young children who have not yet developed full immunological competency, as well as older adults who experience age-related immunological decline. These severe manifestations typically involve systemic infections that are life-threatening and often result in long-lasting morbidities. Many of these pathogenic bacteria are characterized by a carbohydrate capsule against which an effective antibody-mediated response is directed. Unfortunately, immature immune systems cannot readily mount a response to a pure carbohydrate-based vaccine and, even in adults, the immune responses to pure carbohydrates are typically poor and relatively short-lived. It was first demonstrated many decades ago that the conjugation of bacterial polysaccharides to immunogenic carrier proteins (such as bacterial toxoids) can render poorly immunogenic carbohydrates capable of eliciting effective and long-lasting immune responses. However, it was not until the development and licensure of the Haemophilus influenzae type B vaccine in the 1980s that the powerful potential of the technology became apparent. The development of the vaccine was based on the definition of novel chemical conjugation processes that could be reproducibly carried out at manufacturing scale, as well as on the development of novel analytical methods that permitted consistent at-scale production. The technology was advanced further by the development of a highly effective conjugated vaccine for prevention of disease caused by specific serotypes of Streptococcus pneumoniae. Further advances were incorporated in the design of follow-on generations of S. pneumoniae vaccines and in the development of vaccines to prevent severe meningococcal disease. The global impact of these vaccines on mortality and morbidity, particularly among young children, cannot be overstated. xi
The future holds considerable promise as continuing improvements in carbohydrate-protein conjugation chemistries make it possible to develop lower-cost vaccines, particularly for control of S. pneumoniae disease, that can be used more broadly in lower-income countries. In addition, as conjugation science and associated manufacturing processes advance, the potential exists for the development of highly effective and low-cost vaccines against bacterial diseases that place a heavy burden on populations in many lower- and developing middle-income countries. These include improved vaccines for prevention of typhoid as well as the potential development of vaccines to prevent group B streptococcal disease in infants. The promise of vaccines based on carbohydrate conjugation chemistry for prevention of severe bacterial disease worldwide continues to hold true.
Emilio A. Emini Bill & Melinda Gates Foundation
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