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Adjuvants Enhance the Induction of Germinal Center and Antibody Secreting Cells in Spleen and Their Persistence in Bone Marrow of Neonatal Mice

Journal article
Authors A. A. A. Pind
M. Dubik
S. Thorsdottir
A. Meinke
A. M. Harandi
Jan Holmgren
G. Del Giudice
I. Jonsdottir
S. P. Bjarnarson
Published in Frontiers in Immunology
Volume 10
ISSN 1664-3224
Publication year 2019
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Language en
Links dx.doi.org/10.3389/fimmu.2019.02214
Keywords vaccination, neonate, adjuvant, germinal center, antibody-secreting cell persistence, spleen, bone, follicular dendritic cells, heat-labile enterotoxin, splenic marginal, zone, polysaccharide conjugate vaccines, seasonal influenza vaccines, nontoxic b-subunit, intranasal immunization, immune-complexes, cholera-toxin, t-cell, Immunology, ates of america, v113, p1853
Subject categories Microbiology in the medical area, Clinical Laboratory Medicine

Abstract

Immaturity of the immune system contributes to poor vaccine responses in early life. Germinal center (GC) activation is limited due to poorly developed follicular dendritic cells (FDC), causing generation of few antibody-secreting cells (ASCs) with limited survival and transient antibody responses. Herein, we compared the potential of five adjuvants, namely LT-K63, mmCT, MF59, IC31, and alum to overcome limitations of the neonatal immune system and to enhance and prolong responses of neonatal mice to a pneumococcal conjugate vaccine Pnc1-TT. The adjuvants LT-K63, mmCT, MF59, and IC31 significantly enhanced GC formation and FDC maturation in neonatal mice when co-administered with Pnc1-TT. This enhanced GC induction correlated with significantly enhanced vaccine-specific ASCs by LT-K63, mmCT, and MF59 in spleen 14 days after immunization. Furthermore, mmCT, MF59, and IC31 prolonged the induction of vaccine-specific ASCs in spleen and increased their persistence in bone marrow up to 9 weeks after immunization, as previously shown for LT-K63. Accordingly, serum Abs persisted above protective levels against pneumococcal bacteremia and pneumonia. In contrast, alum only enhanced the primary induction of vaccine-specific IgG Abs, which was transient. Our comparative study demonstrated that, in contrast to alum, LT-K63, mmCT, MF59, and IC31 can overcome limitations of the neonatal immune system and enhance both induction and persistence of protective immune response when administered with Pnc1-TT. These adjuvants are promising candidates for early life vaccination.

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