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

• Published in: Frontiers in Immunology
• Main Authors: Aradottir Pind, Audur Anna, Dubik, Magdalena, Thorsdottir, Sigrun, Meinke, Andreas, Harandi, Ali M, Holmgren, Jan, Del Giudice, Giuseppe, Jonsdottir, Ingileif, Bjarnarson, Stefania P
• Other Authors: 1 Department of Immunology, Landspitali, The National University Hospital of Iceland, Reykjavik, Iceland. 2 Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland. 3 Valneva Austria GmbH, Vienna, Austria. 4 Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 5 Vaccine Evaluation Center, BC Children's Hospital Research Institute, The University of British Columbia, Vancouver, BC, Canada. 6 University of Gothenburg Vaccine Research Institute (GUVAX), Department of Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden. 7 GSK Vaccines, Siena, Italy. 8 deCODE Genetics/Amgen, Reykjavík, Iceland.
• Format: Article in Journal/Newspaper
• Language: English
• Published: Frontiers Research Foundation 2019
• Subjects: adjuvant; antibody-secreting cell persistence; bone marrow; germinal center; neonate; protective antibodies; spleen; vaccination; Mati; Vasa; Iceland
• Online Access: http://hdl.handle.net/2336/621110; https://doi.org/10.3389/fimmu.2019.02214

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Download 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. University of Iceland Icelandic Research Fund Landspitali Science Fund European Commission under the VASA European Commission under SHIGETECVAX European Commission under LeiShield-MATI RISE consortia Innovative Medicines Initiative European Commission under the VSV-EBOPLUS ...