A spread-deficient cytomegalovirus for assessment of first-target cells in vaccination.
Human cytomegalovirus (HCMV) is a human pathogen that causes severe disease primarily in the immunocompromised or immunologically immature individual. To date, no vaccine is available. We describe use of a spread-deficient murine CMV (MCMV) as a novel approach for betaherpesvirus vaccination. To generate a spread-deficient MCMV, the conserved, essential gene M94 was deleted. Immunization with MCMV-DeltaM94 is apathogenic and protective against wild-type challenge even in highly susceptible IFNalphabetaR(-/-) mice. MCMV-DeltaM94 was able to induce a robust CD4(+) and CD8(+) T-cell response as well as a neutralizing antibody response comparable to that induced by wild-type infection. Endothelial cells were identified as activators of CD8(+) T cells in vivo. Thus, the vaccination with a spread-deficient betaherpesvirus is a safe and protective strategy and allows the linkage between cell tropism and immunogenicity. Furthermore, genomes of MCMV-DeltaM94 were present in lungs 12 months after infection, revealing first-target cells as sites of genome maintenance.
Mohr
Christian Andreas
CA
Max von Pettenkofer Institute, Ludwig Maximilians University, Pettenkoferstrasse 9a, Munich, Germany.
Arapovic
Jurica
J
Mühlbach
Hermine
H
Panzer
Marc
M
Weyn
Annelies
A
Dölken
Lars
L
Krmpotic
Astrid
A
Voehringer
David
D
Ruzsics
Zsolt
Z
Koszinowski
Ulrich
U
Sacher
Torsten
T
D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D022482:Cytomegalovirus Vaccines / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology*; D005260:Female; D017353:Gene Deletion; D016898:Interferon-alpha / Q000172:deficiency; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018146:Muromegalovirus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D016019:Survival Analysis; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D022482:Cytomegalovirus Vaccines; D016898:Interferon-alpha; D014613:Vaccines, Attenuated; D014764:Viral Proteins; D037521:Virulence Factors
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