The sixth revolution in pediatric vaccinology: immunoengineering and delivery systems

Abstract

Infection is the predominant cause of mortality in early life, and immunization is the most promising biomedical intervention to reduce this burden. However, very young infants fail to respond optimally to most vaccines currently in use, especially neonates. In 2005, Stanley Plotkin proposed that new delivery systems would spur a new revolution in pediatric vaccinology, just as attenuation, inactivation, cell culture of viruses, genetic engineering, and adjuvantation had done in preceding decades. Recent advances in the field of immunoengineering, which is evolving alongside vaccinology, have begun to increasingly influence vaccine formulation design. Historically, the particulate nature of materials used in many vaccine formulations was empiric, often because of the need to stabilize antigens or reduce endotoxin levels. However, present vaccine delivery systems are rationally engineered to mimic the size, shape, and surface chemistry of pathogens, and are therefore often referred to as “pathogen-like particles”. More than a decade from his original assessment, we re-assess Plotkin’s prediction. In addition, we highlight how immunoengineering and advanced delivery systems may be uniquely capable of enhancing vaccine responses in vulnerable populations, such as infants. Impact Immunoengineering and advanced delivery systems are leading to new developments in pediatric vaccinology.Summarizes delivery systems currently in use and development, and prospects for the future.Broad overview of immunoengineering’s impact on vaccinology, catering to Pediatric Clinicians and Immunologists.

Precision Vaccine Development: Cues From Natural Immunity

“…Overall, precision vaccinology can offer the fine tuning or reprogramming of DCs or APCs and antigen specific T cells. Antigen and adjuvant discovery, immunoengineering, vaccine delivery and more importantly increased understanding of human immune responses via dissecting the components of natural infection are fueling a revolution in vaccinology and guiding the development of precision vaccines ( 3 , 240 ), especially for vulnerable infants ( 241 ) and older adults ( 242 ).…”

“…Apart from clean drinking water and sanitation, vaccination is one of the most effective medical interventions to avert infectious diseases ( 1 , 2 ). Despite the great successes of past revolutions in vaccinology, current vaccine technologies may still provide suboptimal protection in vulnerable populations, such as infants ( 1 ) and the elderly ( 3 ). This is an important unmet need for these vulnerable age-groups, but there are important lessons that can be taken from the breadth of vaccinology work performed for future vaccine design.…”

“…Natural immunity achieved by environmental exposure of microorganisms is responsible for immunological imprinting in humans ( 14 ). Yet a number of important caveats need to be addressed, including: i) whether induction of beneficial unnatural immunity can be incorporated into the designing of broad spectrum next generation vaccines [reviewed in ( 15 , 16 )], ii) whether these strategies can specifically induce innate immunity and vaccine efficacy in early and later life [reviewed in ( 6 , 11 ) and ( 17 )], and iii) how can a growing body of vaccine adjuvants, in combination with formulation science of vaccine delivery, such as lipo-nanoparticle based mRNA technologies ( 3 ), be used to open up a new toolbox for vaccinologists [reviewed in ( 12 ) and ( 13 )].…”

Towards Precision Vaccines: Lessons From the Second International Precision Vaccines Conference

“…Dr. David J. Dowling (PVP, Boston Children's Hospital; Harvard Medical School) presented an overview of ongoing work within the PVP to exploit the concepts of trained/ heterologous immunity into next generation adjuvanted vaccine formulations (25,26). Adjuvantation is a key approach to enhancing vaccine immunogenicity (27).…”

“…In 2004 Dr. Stanley Plotkin, referred to as the 'Godfather of Vaccinology', outlined the history of the first five revolutions in vaccinology and outlined some predictions for the next candidate "sixth revolution" (9). In the past two decades, advancements in novel delivery systems have led to remarkable improvements in vaccine translation, positioning it as a sixth revolution in vaccinology (26). During the conference's conclusion panel, he emphasized how the concept of precision vaccines represents the "seventh revolution" in vaccinology wherein the attention of vaccine development is focused on the individual (or group) rather than the herd.…”