Evaluation of a Needle-Free Delivery Platform for Prime-Boost Immunization with DNA and Modified Vaccinia Virus Ankara Vectors Expressing Herpes Simplex Virus 2 Glycoprotein D

We studied the effect of the temporal regulation of herpes simplex virus (HSV) type 1 glycoprotein D (gD-1) expression in Ia+ epidermal cells (EC) and macrophages on virus specific immunity and protection from HSV-2 challenge. gD-1 was expressed on the surface of cells infected with a vaccinia recombinant containing gD-1 under the control of an early vaccinia virus promoter (VP176). It was not expressed in cells infected with a recombinant (VP254) in which gD-1 is controlled by a late vaccinia virus promoter. BALB/c mice immunized with both recombinants seroconverted to HSV-2 as determined by neutralization. However, HSV specific delayed type hypersensitivity (DTH) responses were significantly (p<0.025) higher in VP176 than VP254 immunized animals. Both VP176 and VP254 immunized mice were protected from severe neurological disease due to HSV-2 challenge at 14 days post immunization, but long term protection was observed only in VP176 immunized mice.

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A Novel System for Constructing a Recombinant Highly-Attenuated Vaccinia Virus Strain (LC16m8) Expressing Foreign Genes and Its Application for the Generation of LC16m8-Based Vaccines against Herpes Simplex Virus 2

Japanese Journal of Infectious Diseases ◽

10.7883/yoken.jjid.2017.458 ◽

2018 ◽

Vol 71 (3) ◽

pp. 229-233 ◽

Cited By ~ 4

Author(s):

Natsumi Omura ◽

Tomoki Yoshikawa ◽

Hikaru Fujii ◽

Miho Shibamura ◽

Takuya Inagaki ◽

...

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Vaccinia Virus ◽

Virus Strain ◽

Foreign Genes ◽

Simplex Virus ◽

Herpes Simplex Virus 2 ◽

Vaccinia Virus Strain

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Antiviral Activity of a Single-Domain Antibody Immunotoxin Binding to Glycoprotein D of Herpes Simplex Virus 2

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.03818-14 ◽

2014 ◽

Vol 59 (1) ◽

pp. 527-535 ◽

Cited By ~ 8

Author(s):

Eileen M. Geoghegan ◽

Hong Zhang ◽

Prashant J. Desai ◽

Arya Biragyn ◽

Richard B. Markham

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Single Domain ◽

Surface Glycoprotein ◽

Glycoprotein D ◽

Single Domain Antibody ◽

Domain Antibody ◽

Infected Cells ◽

Simplex Virus ◽

Herpes Simplex Virus 2

ABSTRACTDespite years of research dedicated to preventing the sexual transmission of herpes simplex virus 2 (HSV-2), there is still no protective vaccine or microbicide against one of the most common sexually transmitted infections in the world. Using a phage display library constructed from a llama immunized with recombinant HSV-2 glycoprotein D, we identified a single-domain antibody VHH, R33, which binds to the viral surface glycoprotein D. Although R33 does not demonstrate any HSV-2 neutralization activityin vitro, when expressed with the cytotoxic domain of exotoxin A, the resulting immunotoxin (R33ExoA) specifically and potently kills HSV-2-infected cells, with a 50% neutralizing dilution (IC50) of 6.7 nM. We propose that R33ExoA could be used clinically to prevent transmission of HSV-2 through killing of virus-producing epithelial cells during virus reactivation. R33 could also potentially be used to deliver other cytotoxic effectors to HSV-2-infected cells.

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