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Neonatal Immunology

Neonatal Immunology. How a Lymphomaniac views ( IL )lness. Kristina Abel, PhD CNPRC UC Davis. Age-dependent differences in responses to human vaccines . 1. Vaccine immunogenicity • antibody responses (titer, memory) -infant > adult (polio, hepatitis B, malaria)

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Neonatal Immunology

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

  2. 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.

  3. Unique Features of the Neonatal Immune System • 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

  4. “Normal” Immune Response Treg

  5. B Cell: Ab Infant’s Immune Response

  6. Tasks • 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 developmentalchanges! • Define early, local immune responses in tissues close to pathogen entry site.

  7. Rhesus Macaques

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

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

  10. Tonsillar M Cells - Target for Pediatric HIV Vaccine Neutra, Kozlowski -2006

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

  12. The Mammary Gland - Part of the Mucosal Immune System - 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 Mammary gland - reflective of responses in lung and GALT SLPI CTL Braendtzaeg, 2003 Vaccine, 21:3382

  13. Pregnancy - Induction of a Tolerogenic Milieu Robertson, 2000. Reviews Reprod., 5:164

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

  15. Changes in Lymphocyte Populations during the First Year

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