Open AccessCritical Role for Activation of Antigen-Presenting Cells in Priming of Cytotoxic T Cell Responses After Vaccination with Virus-Like Particles
Author(s) -
Tazio Storni,
Franziska Lechner,
Iris Erdmann,
Thomas Bächi,
Andrea Jegerlehner,
Tilman Dumrese,
Thomas M. Kündig,
Christiane Ruedl,
Martin F. Bachmann
Publication year - 2002
Publication title -
the journal of immunology/the journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.168.6.2880
Subject(s) - ctl* , lymphocytic choriomeningitis , cytotoxic t cell , virology , priming (agriculture) , virus , biology , antigen , vaccinia , ex vivo , in vivo , immunology , in vitro , cd8 , recombinant dna , biochemistry , botany , germination , microbiology and biotechnology , gene
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.