A canarypox vector-expressing cytomegalovirus (CMV) phosphoprotein 65 induces long-lasting cytotoxic T cell responses in human CMV-seronegative subjects.
The major matrix phosphoprotein 65 (pp65) of cytomegalovirus (CMV) is an important target of HLA-restricted cytotoxic T cells (CTL) after natural infection. A canarypox-CMV pp65 recombinant was studied for its ability to induce CMV pp65-specific CTL, helper T lymphocytes, and antibodies in a phase I clinical trial. Twenty-one CMV-seronegative adult volunteers were randomized to receive immunizations at months 0, 1, 3, and 6 with either canarypox-CMV pp65 or placebo. In canarypox-CMV pp65-immunized subjects, pp65-specific CTL were elicited after only 2 vaccinations and were present at months 12 and 26 in all subjects tested. Cell-depletion studies indicated that the CTL were phenotype CD8(+). Peripheral blood mononuclear cells proliferated in response to stimulation with purified pp65, and antibodies specific for pp65 also were detected. Canarypox-CMV pp65 is the first recombinant vaccine to elicit CMV-specific CTL responses, which suggests the potential usefulness of this approach in preventing disease caused by CMV.
Wistar Institute, Philadelphia, PA, USA.
K
K
Berencsi
Z
Z
Gyulai
E
E
Gönczöl
S
S
Pincus
W I
WI
Cox
S
S
Michelson
L
L
Kari
C
C
Meric
M
M
Cadoz
J
J
Zahradnik
S
S
Starr
S
S
Plotkin
D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood*; D000917:Antibody Formation; D000918:Antibody Specificity; D018150:Avipoxvirus / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005822:Genetic Vectors; D006801:Humans; D007111:Immunity, Cellular; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000009:adverse effects*; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000009:adverse effects*
D000914:Antibodies, Viral; D010750:Phosphoproteins; D014614:Vaccines, Synthetic; D014763:Viral Matrix Proteins; D014765:Viral Vaccines; C065418:cytomegalovirus matrix protein 65kDa