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Immune response and cytokine production following immunization with experimental herpes simplex virus 1 (HSV-1) vaccines

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Abstract

Balb/c mice were immunized with the recombinant fusion protein gD1/313 (FpgD1/313 representing the ectodomain of HSV-1 gD), with the non-pathogenic ANGpath gE-del virus, with the plasmid pcDNA3.1-gD expressing full-length gD1 and with the recombinant immediate early (IE) HSV-1 protein ICP27. Specific antibodies against these antigens (as detected by ELISA) reached high titers with the exception of the DNA vaccine. High-grade protection against challenge with the virulent strain SC16 was found following immunization with the pcDNA3.1-gD plasmid and with the gE-del virus. Medium grade, but satisfactory protection developed after immunization with the FpgD1/313 and minimum grade protection was seen upon immunization with the IE/ICP27 polypeptide. A considerable response of peripheral blood cells (PBL) and splenocytes in the lymphocyte transformation test (LTT) was found in mice immunized with FpgD1/313, with the pcDNA3.1-gD plasmid and with the live ANGpathgE-del virus. For lymphocyte stimulation in vitro, the FpgD1/313 antigen was less effective than the purified gD1/313 polypeptide (cleaved off from the fusion protein); both proteins elicited higher proliferation at the 5 μg per 0.1 mL dose than at the 1 μg per 0.1 mL dose. The secretion of Th type 1 (TNF, IFN-γ and IL-2) and Th type 2 (IL-4 and IL-6) cytokines was tested in the medium fluid of purified PBL and splenocyte cultures; their absolute values were expressed in relative indexes. The PBL from FpgD1/313 immunized mice showed increased secretion of both TH1 (TNF) as well as TH2 (IL-4) cytokines (7–10-fold, respectively). Splenocytes from FpgD1/313 immunized mice showed a significant (23-fold) increase in IL-4 production.

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Abbreviations

BSA:

bovine serum albumin

ConA:

concanavalin A

DMEM:

Dulbecco minimal essential medium

ELISA:

enzyme-linked immosorbent assay

FCS:

fetal calf serum

FLgD:

full-length glycoprotein D

FpgD1/313:

fusion protein gD1/313 (313 amino acid ectodomain)

gB:

glycoprotein B

gC:

glycoprotein C

gD:

glycoprotein D

gE:

glycoprotein E

gG:

glycoprotein G

gH:

glycoprotein H

HSV:

herpes simplex virus (human herpes virus)

Hve:

herpesvirus entry mediator

IF:

immunofluorescence

IFN:

interferon

IL:

interleukin

LD50 :

lethal dose 50%

LTT:

lymphocyte transformation test

MoAb:

monoclonal antibody

PBL:

peripheral blood leukocytes

PBS:

phosphate-buffered saline

PFU:

plaque-forming unit

PHA:

phytohemagglutinin

SI:

stimulation index

TNF:

tumor necrosis factor

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Authors and Affiliations

  1. Institute of Virology, Slovak Academy of Sciences, 845 05, Bratislava, Slovakia

    V. Ďurmanová, J. Košovský, I. Režuchová, M. Kúdelová & J. Rajčáni

  2. Department of Immunology, Medical Faculty, Comenius University, Bratislava, Slovakia

    M. Sapák & M. Buc

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  1. V. Ďurmanová
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  2. M. Sapák
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  3. J. Košovský
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  4. I. Režuchová
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  5. M. Kúdelová
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  6. M. Buc
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  7. J. Rajčáni
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Ďurmanová, V., Sapák, M., Košovský, J. et al. Immune response and cytokine production following immunization with experimental herpes simplex virus 1 (HSV-1) vaccines. Folia Microbiol 53, 73–83 (2008). https://doi.org/10.1007/s12223-008-0011-4

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