Journal article
Adenosine deaminase-1 enhances germinal center formation and functional antibody responses to HIV-1 Envelope DNA and protein vaccines
Vaccine, v 38(22), pp 3821-3831
08 May 2020
PMID: 32280045
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Adenosine deaminase-1 (ADA-1) plays both enzymatic and non-enzymatic roles in regulating immune cell function. Mutations in the ADA1 gene account for 15% of heritable severe-combined immunodeficiencies. We determined previously that ADA1 expression defines and is instrumental for the germinal center follicular helper T cell (T-FH) phenotype using in vitro human assays. Herein, we tested whether ADA-1 can be used as an adjuvant to improve vaccine efficacy in vivo. In vitro, ADA-1 induced myeloid dendritic cell (mDC) maturation as measured by increased frequencies of CD40-, CD83-, CD86-, and HLA-DR-positive mDCs. ADA-1 treatment also promoted the secretion of the T-FH-polarizing cytokine IL-6 from mDCs. In the context of an HIV-1 envelope (env) DNA vaccine, co-immunization with plasmid-encoded ADA-1 (pADA) enhanced humoral immunity. Animals co-immunized with env DNA and pADA had significantly increased frequencies of T-FH cells in their draining lymph nodes and increased HIV-binding IgG in serum. Next, mice were co-immunized with subtype C env gp160 DNA and pADA along with simultaneous immunization with matched gp140 trimeric protein. Mice that received env gp160 DNA, pADA, and gp140 glycoprotein had significantly more heterologous HIV-specific binding IgG in their serum. Furthermore, only these mice had detectable neutralizing antibody responses. These studies support the use of ADA-1 as a vaccine adjuvant to qualitatively enhance germinal center responses and represent a novel application of an existing therapeutic agent that can be quickly translated for clinical use. (C) 2020 Elsevier Ltd. All rights reserved.
Metrics
Details
- Title
- Adenosine deaminase-1 enhances germinal center formation and functional antibody responses to HIV-1 Envelope DNA and protein vaccines
- Creators
- Ebony Gary - Drexel UniversityMargaret O'Connor - Drexel UniversityMarita Chakhtoura - Drexel UniversityVirginie Tardif - Drexel UniversityOgan K. Kumova - Drexel UniversityDelphine C. Malherbe - Oregon National Primate Research CenterWilliam F. Sutton - Oregon National Primate Research CenterNancy L. Haigwood - Oregon National Primate Research CenterMichele A. Kutzler - Drexel UniversityElias K. Haddad - Drexel University
- Publication Details
- Vaccine, v 38(22), pp 3821-3831
- Publisher
- Elsevier
- Number of pages
- 11
- Grant note
- 5RO1AI106482-01A; 1U19 AI128910-01 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; Infectious Diseases (and HIV Medicine)
- Web of Science ID
- WOS:000528840000002
- Scopus ID
- 2-s2.0-85083010754
- Other Identifier
- 991019167772104721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology
- Medicine, Research & Experimental