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Herpes Simplex Viruses Whose Replication Can Be Deliberately Controlled as Candidate Vaccines

1
HSF Pharmaceuticals SA, 1814 La Tour-de-Peilz, Switzerland
2
Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL 32610-0266, USA
3
Hospital Universitario La Paz-IdiPAZ, 28046 Madrid, Spain
4
CIBER de Bioingenieria, Biomateriales y Nanomedicina, CIBER-BBN, 28046 Madrid, Spain
*
Author to whom correspondence should be addressed.
Vaccines 2020, 8(2), 230; https://doi.org/10.3390/vaccines8020230
Received: 8 April 2020 / Revised: 12 May 2020 / Accepted: 13 May 2020 / Published: 18 May 2020
(This article belongs to the Special Issue Vaccine Development for Herpes Simplex Viruses)
Over the last few years, we have been evaluating a novel paradigm for immunization using viruses or virus-based vectors. Safety is provided not by attenuation or inactivation of vaccine viruses, but by the introduction into the viral genomes of genetic mechanisms that allow for stringent, deliberate spatial and temporal control of virus replication. The resulting replication-competent controlled viruses (RCCVs) can be activated to undergo one or, if desired, several rounds of efficient replication at the inoculation site, but are nonreplicating in the absence of activation. Extrapolating from observations that attenuated replicating viruses are better immunogens than replication-defective or inactivated viruses, it was hypothesized that RCCVs that replicate with wild-type-like efficiency when activated will be even better immunogens. The vigorous replication of the RCCVs should also render heterologous antigens expressed from them highly immunogenic. RCCVs for administration to skin sites or mucosal membranes were constructed using a virulent wild-type HSV-1 strain as the backbone. The recombinants are activated by a localized heat treatment to the inoculation site in the presence of a small-molecule regulator (SMR). Derivatives expressing influenza virus antigens were also prepared. Immunization/challenge experiments in mouse models revealed that the activated RCCVs induced far better protective immune responses against themselves as well as against the heterologous antigens they express than unactivated RCCVs or a replication-defective HSV-1 strain. Neutralizing antibody and proliferation responses mirrored these findings. We believe that the data obtained so far warrant further research to explore the possibility of developing effective RCCV-based vaccines directed to herpetic diseases and/or diseases caused by other pathogens. View Full-Text
Keywords: herpesvirus; HSV-1; candidate vaccine; vaccine vector; live vaccine; replication-competent controlled herpesvirus; HSV-1; candidate vaccine; vaccine vector; live vaccine; replication-competent controlled
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Voellmy, R.; Bloom, D.C.; Vilaboa, N. Herpes Simplex Viruses Whose Replication Can Be Deliberately Controlled as Candidate Vaccines. Vaccines 2020, 8, 230.

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