TY - JOUR
T1 - Induction of herpes simplex virus type 1 cell-to-cell spread inhibiting antibodies by a calcium phosphate nanoparticle-based vaccine
AU - Kopp, Mathis
AU - Aufderhorst, Ulrich Wilhelm
AU - Alt, Mira
AU - Dittmer, Ulf
AU - Eis-Hübinger, Anna Maria
AU - Giebel, Bernd
AU - Roggendorf, Michael
AU - Epple, Matthias
AU - Krawczyk, Adalbert
N1 - Publisher Copyright:
© 2018 The Authors
PY - 2019/2
Y1 - 2019/2
N2 - Herpes simplex viruses 1 and 2 are among the most ubiquitous human infections and persist lifelong in their host. Upon primary infection or reactivation from ganglia, the viruses spread by direct cell–cell contacts (cell-to-cell spread) and thus escape from the host immune response. We have developed a monoclonal antibody (mAb 2c), which inhibits the HSV cell-to-cell spread, thereby protecting from lethal genital infection and blindness in animal models. In the present study we have designed a nanoparticle-based vaccine to induce protective antibody responses exceeding the cell-to-cell spread inhibiting properties of mAb 2c. We used biodegradable calcium phosphate (CaP) nanoparticles coated with a synthetic peptide that represents the conformational epitope on HSV-1 gB recognized by mAb 2c. The CaP nanoparticles additionally contained a TLR-ligand CpG m and were formulated with adjuvants to facilitate the humoral immune response. This vaccine effectively protected mice from lethal HSV-1 infection by inducing cell-to-cell spread inhibiting antibodies.
AB - Herpes simplex viruses 1 and 2 are among the most ubiquitous human infections and persist lifelong in their host. Upon primary infection or reactivation from ganglia, the viruses spread by direct cell–cell contacts (cell-to-cell spread) and thus escape from the host immune response. We have developed a monoclonal antibody (mAb 2c), which inhibits the HSV cell-to-cell spread, thereby protecting from lethal genital infection and blindness in animal models. In the present study we have designed a nanoparticle-based vaccine to induce protective antibody responses exceeding the cell-to-cell spread inhibiting properties of mAb 2c. We used biodegradable calcium phosphate (CaP) nanoparticles coated with a synthetic peptide that represents the conformational epitope on HSV-1 gB recognized by mAb 2c. The CaP nanoparticles additionally contained a TLR-ligand CpG m and were formulated with adjuvants to facilitate the humoral immune response. This vaccine effectively protected mice from lethal HSV-1 infection by inducing cell-to-cell spread inhibiting antibodies.
KW - Antibodies
KW - CaP nanoparticles
KW - Cell-to-cell spread
KW - Herpes simplex virus
UR - http://www.scopus.com/inward/record.url?scp=85060209587&partnerID=8YFLogxK
U2 - 10.1016/j.nano.2018.12.002
DO - 10.1016/j.nano.2018.12.002
M3 - Article
C2 - 30594660
AN - SCOPUS:85060209587
SN - 1549-9634
VL - 16
SP - 138
EP - 148
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
ER -