Enhanced germinal center reaction by targeting vaccine antigen to major histocompatibility complex class II molecules

Enhancing the germinal center (GC) reaction is a prime objective in vaccine development. Targeting of antigen to MHCII on APCs has previously been shown to increase antibody responses, but the underlying mechanism has been unclear. We have here investigated the GC reaction after targeting antigen to...

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Bibliographic Details
Published in:	npj vaccines Vol. 4; no. 1; p. 9
Main Authors:	Andersen, Tor Kristian, Huszthy, Peter C., Gopalakrishnan, Ramakrishna P., Jacobsen, Johanne T., Fauskanger, Marte, Tveita, Anders A., Grødeland, Gunnveig, Bogen, Bjarne
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 11-02-2019 Nature Publishing Group
Subjects:	631/250/2152/2153/1291 631/250/2152/2153/1982 631/250/255/1578 631/250/590/1991 Antigens Biomedical and Life Sciences Biomedicine Immunoglobulins Infectious Diseases Medical Microbiology Multiple myeloma Public Health Vaccine Vaccines Virology
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Summary:	Enhancing the germinal center (GC) reaction is a prime objective in vaccine development. Targeting of antigen to MHCII on APCs has previously been shown to increase antibody responses, but the underlying mechanism has been unclear. We have here investigated the GC reaction after targeting antigen to MHCII in (i) a defined model with T and B cells of known specificity using adjuvant-free vaccine proteins, and (ii) an infectious disease model using a DNA vaccine. MHCII-targeting enhanced presentation of peptide: MHCII on APCs, and increased the numbers of GC B cells, T FH , and plasma cells. Antibodies appeared earlier and levels were increased. BCR of GC B cells and serum antibodies had increased avidity for antigen. The improved responses required cross-linking of BCR and MHCII in either cis or trans . The enhanced GC reaction induced by MHCII-targeting of antigen has clear implications for design of more efficient subunit vaccines. Vaccine targeting: Enhancement of responses by MHC class II targeting The germinal center (GC) reaction underpins the robust antibody responses that are the goal of most vaccine approaches. Bjarne Bogen and colleagues at the University of Oslo develop an adjuvant-free engineered vaccine that can enhance the GC reaction. The vaccine is composed of an antibody fragment targeting a mouse major histocompatability complex (MHC) class II (I-E d ) linked to an experimental myeloma antigen. When tested in B-cell and T-cell receptor transgenic mice specific for the myeloma antigen, GC responses, antibody titers and affinity as well as B and T cell proliferation are all enhanced compared to non-MHC class II targeted vaccine. MHC class II targeting can also enhance antibody responses to influenza antigen using a DNA vaccination approach in wildtype mice. Targeting antigens to MHC class II enhances the GC reaction and has potential implications for the design of more potent and durable vaccines.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2059-0105 2059-0105
DOI:	10.1038/s41541-019-0101-0