Immunization by replication-competent controlled herpesvirus vectors

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

doi:10.1101/299230

Cited by 2 publications

(3 citation statements)

References 52 publications

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“…Previous studies from several groups have established that HSV-1 is a safe and effective live vaccine vector, which triggers robust immune responses against multiple infectious pathogens including HIV and rotavirus, among others (45)(46)(47)(48). Herein, we generated a HSV-1-derived vaccine against influenza virus, a significant human and animal respiratory viral pathogen.…”

Section: Discussionmentioning

confidence: 99%

“…There are a number of groups currently working on HSV-vectored vaccines against a number of human and animal pathogens. Multiple approaches ranging from HSV based amplicons, replication defective, attenuated or conditionally defective vectors have been considered (45)(46)(47)(48).…”

Section: Discussionmentioning

confidence: 99%

“…This BAC plasmid was used to construct VC2-HA. Briefly, the new VC2-HA plasmid were constructed in Escherichia coli SW105 cells, using the two-step bacteriophage lambda Redmediated recombination system, as described previously (15,46). The pCAGGS-PR8-HA sequence of was amplified by PCR using primers P1 and P2.…”

Section: Methodsmentioning

confidence: 99%

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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. 2021

Preprint

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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. A live viral vector technology should exhibit safety, immunogenicity, effectiveness in the presence of pre-existing immunity, and the ability to induce mucosal immune responses. Here, we used VC2, an established Herpes Simplex Virus type 1 vaccine vector, to express the influenza HA 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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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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. 2021

Preprint

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Immunization by Replication-Competent Controlled Herpesvirus Vectors

Bloom

Tran

Feller

et al. 2018

J Virol

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We hypothesized that vigorous replication of a pathogen may be critical for eliciting the most potent and balanced immune response against it. Hence, attenuation/inactivation (as in conventional vaccines) should be avoided. Instead, the necessary safety should be provided by placing replication of the pathogen under stringent control and by activating time-limited replication of the pathogen strictly in an administration region in which pathology cannot develop. Immunization will then occur in the context of highly efficient pathogen replication and uncompromised safety. We found that localized activation in mice of efficient but limited replication of a replication-competent controlled herpesvirus vector resulted in a greatly enhanced immune response to the virus or an expressed heterologous antigen. This finding supports the above-mentioned hypothesis and suggests that the vectors may be promising novel agents worth exploring for the prevention/mitigation of infectious diseases for which efficient vaccination is lacking, in particular in immunocompromised patients.

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Immunization by replication-competent controlled herpesvirus vectors

Cited by 2 publications

References 52 publications

A Herpes Simplex Virus Type-1-derived influenza vaccine induces balanced adaptive immune responses and protects mice from lethal influenza virus challenge

A Herpes Simplex Virus Type-1-derived influenza vaccine induces balanced adaptive immune responses and protects mice from lethal influenza virus challenge

Immunization by Replication-Competent Controlled Herpesvirus Vectors

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