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Article

Production Strategies for Pentamer-Positive Subviral Dense Bodies as a Safe Human Cytomegalovirus Vaccine

1
Institute for Virology, University Medical Center of the Johannes Gutenberg-University Mainz, D-55131 Mainz, Germany
2
Vakzine Projekt Management GmbH, Mellendorfer Str. 9, D-30625 Hannover, Germany
*
Author to whom correspondence should be addressed.
Vaccines 2019, 7(3), 104; https://doi.org/10.3390/vaccines7030104
Received: 17 July 2019 / Revised: 26 August 2019 / Accepted: 28 August 2019 / Published: 1 September 2019
(This article belongs to the Special Issue Cytomegalovirus Infection and Vaccine Development)
Infections with the human cytomegalovirus (HCMV) are associated with severe clinical manifestations in children following prenatal transmission and after viral reactivation in immunosuppressed individuals. The development of an HCMV vaccine has long been requested but there is still no licensed product available. Subviral dense bodies (DB) are immunogenic in pre-clinical models and are thus a promising HCMV vaccine candidate. Recently, we established a virus based on the laboratory strain Towne that synthesizes large numbers of DB containing the pentameric protein complex gH/gL/UL128-131 (Towne-UL130repΔGFP). The work presented here focuses on providing strategies for the production of a safe vaccine based on that strain. A GMP-compliant protocol for DB production was established. Furthermore, the DB producer strain Towne-UL130rep was attenuated by deleting the UL25 open reading frame. Additional genetic modifications aim to abrogate its capacity to replicate in vivo by conditionally expressing pUL51 using the Shield-1/FKBP destabilization system. We further show that the terminase inhibitor letermovir can be used to reduce infectious virus contamination of a DB vaccine by more than two orders of magnitude. Taken together, strategies are provided here that allow for the production of a safe and immunogenic DB vaccine for clinical testing. View Full-Text
Keywords: cytomegalovirus; vaccine; dense bodies; congenital infection; safety vector; pentamer complex; gH/gL/UL128-131 cytomegalovirus; vaccine; dense bodies; congenital infection; safety vector; pentamer complex; gH/gL/UL128-131
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MDPI and ACS Style

Gogesch, P.; Penner, I.; Krauter, S.; Büscher, N.; Grode, L.; Aydin, I.; Plachter, B. Production Strategies for Pentamer-Positive Subviral Dense Bodies as a Safe Human Cytomegalovirus Vaccine. Vaccines 2019, 7, 104. https://doi.org/10.3390/vaccines7030104

AMA Style

Gogesch P, Penner I, Krauter S, Büscher N, Grode L, Aydin I, Plachter B. Production Strategies for Pentamer-Positive Subviral Dense Bodies as a Safe Human Cytomegalovirus Vaccine. Vaccines. 2019; 7(3):104. https://doi.org/10.3390/vaccines7030104

Chicago/Turabian Style

Gogesch, Patricia, Inessa Penner, Steffi Krauter, Nicole Büscher, Leander Grode, Inci Aydin, and Bodo Plachter. 2019. "Production Strategies for Pentamer-Positive Subviral Dense Bodies as a Safe Human Cytomegalovirus Vaccine" Vaccines 7, no. 3: 104. https://doi.org/10.3390/vaccines7030104

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