While the greatest number of vaccines is administered to the very young, vaccine preventable infections remain a major cause of morbidity and mortality, especially for the newborn. To improve vaccine-mediated protection early in life, the investigators will identify biomarkers that predict protective efficacy and garner insight into the underlying mechanisms of vaccine-mediated protection. Systems biology approaches ("OMICs") applied to vaccinology, i.e., systems vaccinology, has revolutionized the field with an unbiased identification of pathways relevant to vaccine-induced immune responses. However, thus far systems vaccinology has focused primarily on adults, with few studies conducted in children and infants, and none in newborns. This study will bridge this gap by conducting a comprehensive systems vaccinology study in newborns. Specifically, the investigators will determine the molecular pathways that are associated with successful neonatal immunization with hepatitis B virus vaccine (HBV). HBV is the ideal model because i) it is highly (>90%) effective; ii) it has a well-established correlate of protection (CoP; anti-hepatitis surface antigen antibody (anti-HBs)); iii) there is substantial variation in anti-HBs titers and quantifiable inter-subject variability is essential for systems biological approaches; iv) it is highly relevant as HBV is given at birth in the U.S. and most developing countries; v) it is amenable to in vivo manipulation with another regularly administered neonatal vaccine, Bacille Calmette-Guérin (BCG), which will greatly enhance detection of relevant signatures. As complex networks of functional interactions among genes and proteins drive the response to immunization, the investigators will integrate transcriptomic, proteomic and immune phenotyping approaches. Importantly, the investigators have successfully adapted these experimental platforms to be fully operational within the small blood volumes obtainable in newborns. The investigators have also developed in vitro systems amenable to experimental manipulation on the cellular and molecular level to identify cause-effect relationships. Pilot data prove feasibility of collecting the relevant high-quality samples according to stringent standard operating procedures, processing them and delivering cogent OMIC data suggesting vaccine-specific 'signatures' in the human newborn. This HIPC will identify biomarkers of neonatal HBV immunogenicity by pursuing the following Overall Specific Aims: