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

Abstract

Other than clean drinking water, vaccines have been the most effective public health intervention in human history, yet their full potential is still untapped. To date, vaccine development has been largely limited to empirical approaches focused on infectious diseases and has targeted entire populations, potentially disregarding distinct immunity in vulnerable populations such as infants, elders, and the immunocompromised. Over the past few decades innovations in genetic engineering, adjuvant discovery, formulation science, and systems biology have fueled rapid advances in vaccine research poised to consider demographic factors (e.g., age, sex, genetics, and epigenetics) in vaccine discovery and development. Current efforts are focused on leveraging novel approaches to vaccine discovery and development to optimize vaccinal antigen and, as needed, adjuvant systems to enhance vaccine immunogenicity while maintaining safety. These approaches are ushering in an era of precision vaccinology aimed at tailoring immunization for vulnerable populations with distinct immunity. To foster collaboration among leading vaccinologists, government, policy makers, industry partners, and funders from around the world, the Precision Vaccines Program at Boston Children's Hospital hosted the 2 nd International Precision Vaccines Conference (IPVC) at Harvard Medical School on the 17 th-18 th October 2019. The conference convened experts in vaccinology, including vaccine formulation and adjuvantation, immunology, cell signaling, systems biology, biostatistics, bioinformatics, as well as vaccines for non-infectious indications such as cancer and opioid use disorder. Herein we review highlights from the 2 nd IPVC and discuss key concepts in the field of precision vaccines.

Human Newborn Monocytes Demonstrate Distinct BCG-Induced Primary and Trained Innate Cytokine Production and Metabolic Activation In Vitro

“…Innate immune memory responses are complex and depend on the age of the exposed, timing of exposure and properties of the stimulus. Of note, while neonatal Mos express similar quantities of TLRs as their adult counterparts ( 55 , 56 ) the downstream consequences of TLR activation are distinct with age ( 8 ). Whether the BCG-induced tolerance to LPS in neonatal Mos observed in our study is related to TLR-mediated epigenetic reprogramming will be an important area of future investigation.…”

“…Much remains to be learned about alterations in neonatal immune function following infection/vaccination during this critical period of immune system adaptation and development. Using BCG as a model to characterize distinct trained immunity in newborns may inform discovery and development of novel adjuvants, vaccines and immunotherapies for this vulnerable population ( 56 ).…”

Editorial: Immunity in Compromised Newborns

“…Active immunization against specific pathogens in early life is often hampered by impaired initiation, immunogenicity, antibody production and cell-mediated response, requiring highly species-, age-and patient-specific vaccine approaches (23). These concerns of inadequate vaccine responses in newborns may be particularly relevant for preterm infants and Kulkarni-Munje et al showed that although Indian preterm infants mounted adequate systemic immune responses to the majority of antigens of a pentavalent vaccine, diminished immunological memory remained a concern, relative to term infants.…”

“…Active immunization against specific pathogens in early life is often hampered by impaired initiation, immunogenicity, antibody production and cell-mediated response, requiring highly species-, age- and patient-specific vaccine approaches ( 23 ). These concerns of inadequate vaccine responses in newborns may be particularly relevant for preterm infants and Kulkarni-Munje et al.…”

Precision Vaccine Development: Cues From Natural Immunity

“…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 ).…”