Antigen-specific T cell responses induced by Towne cytomegalovirus (CMV) vaccine in CMV-seronegative vaccine recipients.
BACKGROUND
Towne cytomegalovirus (CMV) vaccine is safe and immunogenic, though its protective efficacy has yet to be optimized.


OBJECTIVE
Describe antigen-specific T cell responses to Towne vaccination.


METHODS
3000 pfu Towne CMV vaccine were given to 12 CMV-seronegative volunteers. CMV-specific CD4+ and CD8+ T cell proliferation and IFNgamma expression were measured by flow cytometry after stimulation with CMV lysate or peptides.


RESULTS
All vaccinees developed CD4+ and CD8+ T cell proliferation and CD4+ T cell IFNgamma responses to multiple CMV antigens, but their CD8+ T cells had low or undetectable IFNgamma responses to pp65 peptide pool. The seven HLA-A2+ subjects had higher CD8+ T cell proliferation and IFNgamma responses to IE than pp65, and two never developed CD8+ T cell IFNgamma responses to pp65. Peak CD4+ T cell IFNgamma responses to CMV lysate were lower than values observed in natural CMV seropositives. Initial CD4+ and CD8+ T cell responses to lysate and pp65 waned after 12 months to levels that were lower than those in healthy CMV seropositives, while vaccinees' CD8+ T cell responses to IE were robust and prolonged.


CONCLUSIONS
Correlating CMV antigen-specific T cell responses with clinical protective efficacy may facilitate future CMV vaccine development.
Jacobson
Mark A
MA
Positive Health Program, Department of Medicine, University of California San Francisco, 4th Floor, 995 Potrero, San Francisco, CA 94110, USA. mjacobson@php.ucsf.edu
Sinclair
Elizabeth
E
Bredt
Barry
B
Agrillo
Laurie
L
Black
Douglas
D
Epling
C Lorrie
CL
Carvidi
Alexander
A
Ho
Terence
T
Bains
Raji
R
Adler
Stuart P
SP
D000293:Adolescent; D000328:Adult; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000517:prevention & control; D022482:Cytomegalovirus Vaccines / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000276:immunology; D014763:Viral Matrix Proteins / Q000276:immunology
D000956:Antigens, Viral; D022482:Cytomegalovirus Vaccines; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; D007371:Interferon-gamma