Immunization by Replication-Competent Controlled Herpesvirus Vectors

Bloom, David C.; Tran, Robert K.; Feller, Joyce A.; Voellmy, Richard

doi:10.1128/jvi.00616-18

Cited by 14 publications

(30 citation statements)

References 53 publications

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“…Three weeks later, neutralizing antibody titers were assessed and responder cell frequencies determined in a lymphoproliferation assay. Results obtained from such an experiment employing recombinant HSV-GS11 are represented in Figure 3 (originally reported in Reference [40] Immunization with activated HSV-GS11 induced a several-fold higher level of EIV-specific neutralizing antibodies than immunization with unactivated HSV-GS11. No neutralizing antibodies were detected in sera from animals immunized with HSV-GS3.…”

Section: Immune Response To a Vectored Antigen Of Another Pathogenmentioning

confidence: 99%

“…Most of the results discussed under this heading were originally disclosed in References [39][40][41].…”

Section: Immune Responses To Activated Rccvsmentioning

confidence: 99%

“…The immune response to activated RCCVs was evaluated in a stringent mouse footpad lethal challenge model [40]. In one such experiment, groups of adult outbred mice were inoculated with RCCVs HSV-GS3 or HSV-GS7 (50,000 PFU) on the footpads of their rear feet.…”

Section: Anti-herpetic Immune Responsementioning

confidence: 99%

“…The data are presented as percent survival (at 26 days post challenge) for each treatment group (n = 20 for each HSV-GS3 or HSV-GS7 group; n = 10 for the mock-immunized group; *, p ≤ 0.05). This figure is based on data reported in Reference [40].…”

Section: Anti-herpetic Immune Responsementioning

confidence: 99%

“…The data are presented as the responder cell frequency of each experimental group; *, p ≤ 0.05). See Reference [40] for the original report of the results shown in this figure.…”

Section: Immune Response To a Vectored Antigen Of Another Pathogenmentioning

confidence: 99%

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

Voellmy¹,

Bloom

Vilaboa

2020

Vaccines

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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.

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Section: Immune Response To a Vectored Antigen Of Another Pathogenmentioning

confidence: 99%

“…Most of the results discussed under this heading were originally disclosed in References [39][40][41].…”

Section: Immune Responses To Activated Rccvsmentioning

confidence: 99%

Section: Anti-herpetic Immune Responsementioning

confidence: 99%

Section: Anti-herpetic Immune Responsementioning

confidence: 99%

“…The data are presented as the responder cell frequency of each experimental group; *, p ≤ 0.05). See Reference [40] for the original report of the results shown in this figure.…”

Section: Immune Response To a Vectored Antigen Of Another Pathogenmentioning

confidence: 99%

See 3 more Smart Citations

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

Voellmy¹,

Bloom

Vilaboa

2020

Vaccines

Self Cite

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A Herpes Simplex Virus Type‐1‐Derived Influenza Vaccine Induces Balanced Adaptive Immune Responses and Protects Mice From Lethal Influenza Virus Challenge

Rider,

Dulin,

Uche

et al. 2024

Journal of Medical Virology

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Influenza virus is a major respiratory viral pathogen responsible for the deaths of hundreds of thousands worldwide each year. Current vaccines provide protection primarily by inducing strain‐specific antibody responses with the requirement of a match between vaccine strains and circulating strains. It has been suggested that anti‐influenza T‐cell responses, in addition to antibody responses may provide the broadest protection against different flu strains. Therefore, to address this urgent need, it is desirable to develop a vaccine candidate with an ability to induce balanced adaptive immunity including cell mediated immune responses. Here, we explored the potential of VC2, a well‐characterized Herpes Simplex Virus type 1 vaccine vector, as a live attenuated influenza vaccine candidate. We generated a recombinant VC2 virus expressing the influenza A hemagglutinin protein. We show that this virus is capable of generating potent and specific anti‐influenza humoral and cell‐mediated immune responses. We further show that a single vaccination with the VC2‐derived influenza vaccine protects mice from lethal challenge with influenza virus. Our data support the continued development of VC2‐derived influenza vaccines for protection of human populations from both seasonal and pandemic strains of influenza. Finally, our results support the potential of VC2‐derived vaccines as a platform for the rapid development of vaccines against emerging and established pathogens, particularly respiratory pathogens.

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A chemical method for generating live-attenuated, replication-defective DNA viruses for vaccine development

Jaijyan

Govindasamy

Lee

et al. 2022

Cell Reports Methods

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Immunization by Replication-Competent Controlled Herpesvirus Vectors

Cited by 14 publications

References 53 publications

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

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

A Herpes Simplex Virus Type‐1‐Derived Influenza Vaccine Induces Balanced Adaptive Immune Responses and Protects Mice From Lethal Influenza Virus Challenge

A chemical method for generating live-attenuated, replication-defective DNA viruses for vaccine development

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