Critical role for activation of antigen-presenting cells in priming of cytotoxic T cell responses after vaccination with virus-like particles.
Virus-like particles (VLPs) are known to induce strong Ab responses in the absence of adjuvants. In addition, VLPs are able to prime CTL responses in vivo. To study the efficiency of this latter process, we fused peptide p33 derived from lymphocytic choriomeningitis virus to the hepatitis B core Ag, which spontaneously assembles into VLPs (p33-VLPs). These p33-VLPs were efficiently processed in vitro and in vivo for MHC class I presentation. Nevertheless, p33-VLPs induced weak CTL responses that failed to mediate effective protection from viral challenge. However, if APCs were activated concomitantly in vivo using either anti-CD40 Abs or CpG oligonucleotides, the CTL responses induced were fully protective against infection with lymphocytic choriomeningitis virus or recombinant vaccinia virus. Moreover, these CTL responses were comparable to responses generally induced by live vaccines, because they could be measured in primary ex vivo (51)Cr release assays. Thus, while VLPs alone are inefficient at inducing CTL responses, they become very powerful vaccines if applied together with substances that activate APCs.
Storni
Tazio
T
Cytos Biotechnology, AG, Department of Dermatology and Institute of Experimental Immunology, University Hospital, and Elektronenmikroskopisches Zentrallabor Universität, Zurich, Switzerland.
Lechner
Franziska
F
Erdmann
Iris
I
Bächi
Thomas
T
Jegerlehner
Andrea
A
Dumrese
Tilman
T
Kündig
Thomas M
TM
Ruedl
Christiane
C
Bachmann
Martin F
MF
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D017951:Antigen Presentation / Q000235:genetics; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000956:Antigens, Viral / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D002860:Chromium Radioisotopes; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006023:Glycoproteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D006512:Hepatitis B Core Antigens / Q000235:genetics / Q000276:immunology; D007271:Injections, Intradermal; D007279:Injections, Subcutaneous; D007739:L Cells; D008213:Lymphocyte Activation / Q000276:immunology*; D008216:Lymphocytic Choriomeningitis / Q000517:prevention & control; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology; D014407:Tumor Cells, Cultured; D014615:Vaccinia / Q000517:prevention & control; D014764:Viral Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014771:Virion / Q000235:genetics / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D019013:CD40 Antigens; C408982:CPG-oligonucleotide; D002860:Chromium Radioisotopes; D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D006512:Hepatitis B Core Antigens; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; D014765:Viral Vaccines; C094244:glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus