Neonatal Immunology Kristina Abel, PhD CNPRC UC Davis How a Lymphomaniac views ( IL )lness

Age-dependent differences in responses to human vaccines 1. Vaccine immunogenicity antibody responses (titer, memory) -infant > adult (polio, hepatitis B, malaria) T cell responses (cytokine secretion, function) - adult > children > infants - primed in infants, even in presence of maternal Ab (measles, mumps) 2. Vaccine efficacy BCG, malaria vaccines - infants > children, low/no efficacy in adults - protect against severe disease Thus, adult vaccine responses are not reliable predictors of vaccine immunogenicity or efficacy in infants.

Hematological changes in the first few months of life naïve/ memory T vs. B cells T cell subsets B cell development and maternal Ab Development of normal flora at mucosal sites Implications for mucosal immune responses? Influence of nutrition, including breast-feeding Immune system is immature - Immune system is developing: differences in quality and quantity Unique Features of the Neonatal Immune System

Treg “Normal” Immune Response

Infant’s Immune Response B Cell: Ab

Determine developmental changes in immune cell populations on the phenotypic and functional level. intracellular signaling pathways influence of mDC on T cell function generation of multifunctional T cells relationship between positive and negative regulation of T cell function induction and survival of memory T cells Apply knowledge to pediatric vaccine design. dose-dependency timing: age factor testing of multiple routes and their combination adjuvants/ DC priming magnitude, quality and survival of memory T cell populations Analysis of pathogen and/or vaccine-induced immune responses in relation to normal developmental changes! Define early, local immune responses in tissues close to pathogen entry site. Tasks

Rhesus Macaques

Design a novel oral pediatric combination vaccine using a recombinant attenuated Mycobacterium tuberculosis vector expressing SIV/HIV genes.

Geographical Overlap between HIV and M.tb Infections HIV + TB

Neutra, Kozlowski Tonsillar M Cells - Target for Pediatric HIV Vaccine

Tonsil Breast-milk transmission Virus entry: oral mucosa tonsil intestine

Braendtzaeg, 2003 Vaccine, 21:3382 The Mammary Gland - Part of the Mucosal Immune System Mammary gland - reflective of responses in lung and GALT - PP and tonsils are developed at birth, but GC lack for a few weeks - mucosal immunity is passively acquired from the mother via breast milk - breast -feeding is estimated to prevent up to 3 million death/ year in newborns CTL SLPI

Robertson, Reviews Reprod., 5:164 Pregnancy - Induction of a Tolerogenic Milieu

IgG only! Maternal Antibodies Immunity transmitted from the Mother to the Fetus

Changes in Lymphocyte Populations during the First Year