Antigen bivalency of antigen-presenting cell-targeted vaccines increases B cell responses

Daniëla Maria Hinke; Tor Kristian Andersen; Ramakrishna Prabhu Gopalakrishnan; Lise Madelene Skullerud; Ina Charlotta Werninghaus; Gunnveig Grødeland; Even Fossum; Ranveig Braathen; Bjarne Bogen

doi:10.1016/j.celrep.2022.110901

Antigen bivalency of antigen-presenting cell-targeted vaccines increases B cell responses

Cell Rep. 2022 May 31;39(9):110901. doi: 10.1016/j.celrep.2022.110901.

Authors

Daniëla Maria Hinke¹, Tor Kristian Andersen¹, Ramakrishna Prabhu Gopalakrishnan², Lise Madelene Skullerud², Ina Charlotta Werninghaus², Gunnveig Grødeland¹, Even Fossum¹, Ranveig Braathen³, Bjarne Bogen⁴

Affiliations

¹ K.G. Jebsen Centre for Influenza Vaccine Research, Institute of Clinical Medicine, University of Oslo, Oslo 0372, Norway; Department of Immunology (IMM), University of Oslo and Oslo University Hospital, Oslo 0372, Norway.
² Department of Immunology (IMM), University of Oslo and Oslo University Hospital, Oslo 0372, Norway.
³ K.G. Jebsen Centre for Influenza Vaccine Research, Institute of Clinical Medicine, University of Oslo, Oslo 0372, Norway; Department of Immunology (IMM), University of Oslo and Oslo University Hospital, Oslo 0372, Norway. Electronic address: ranveig.braathen@medisin.uio.no.
⁴ K.G. Jebsen Centre for Influenza Vaccine Research, Institute of Clinical Medicine, University of Oslo, Oslo 0372, Norway; Department of Immunology (IMM), University of Oslo and Oslo University Hospital, Oslo 0372, Norway. Electronic address: bjarne.bogen@medisin.uio.no.

PMID: 35649357
DOI: 10.1016/j.celrep.2022.110901

Abstract

Antibodies are important for vaccine efficacy. Targeting antigens to antigen-presenting cells (APCs) increases antibody levels. Here, we explore the role of antigen valency in MHC class II (MHCII)-targeted vaccines delivered as DNA. We design heterodimeric proteins that carry either two identical (bivalent vaccines), or two different antigens (monovalent vaccines). Bivalent vaccines with two identical influenza hemagglutinins (HA) elicit higher amounts of anti-HA antibodies in mice than monovalent versions with two different HAs. Bivalent vaccines increase the levels of germinal center (GC) B cells and long-lived plasma cells. Only HA-bivalent vaccines completely protect mice against challenge with homologous influenza virus. Similar results are obtained with other antigens by targeting CD11c and Xcr1 on dendritic cells (DCs) or when administering the vaccine as protein with adjuvant. Bivalency probably increases B cell responses by cross-linking BCRs in readily observable DC-B cell synapses. These results are important for generating potent APC-targeted vaccines.

Keywords: CP: Immunology; DC targeting; DC-B cell synapse; DNA vaccine; T cell responses; antibody responses; antigen multivalency; heterodimer; influenza; myeloma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Viral
Antigen-Presenting Cells
Cancer Vaccines*
Hemagglutinins
Influenza Vaccines*
Mice
Vaccines, Combined
Vaccines, DNA* / genetics

Substances

Antibodies, Viral
Cancer Vaccines
Hemagglutinins
Influenza Vaccines
Vaccines, Combined
Vaccines, DNA