Efficacy of Recombinant Herpes Simplex Virus 1 Glycoprotein D Candidate Vaccines in Mice

Durmanová, V. and Moško, T. and Sapák, M. and Košovský, J. and Režuchová, I. and Buc, M. and Rajcáni, J. (2006) Efficacy of Recombinant Herpes Simplex Virus 1 Glycoprotein D Candidate Vaccines in Mice. Acta Microbiologica et Immunologica Hungarica, 53 (4). pp. 459-477. ISSN 1217-8950

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Abstract

To compare the immunogenity of the herpes simplex virus 1 (HSV-1/HHV-1) recombinant glycoprotein D (gD1), as a potential protective vaccine, Balb/c mice were immunized with either gD1/313 (the ectodomain of the gD1 fusion protein consisting of 313 amino acid residues), or the plasmid pcDNA3.1-gD (coding for a full length gD1 protein, FLgD1). A live attenuated HSV-l (deleted in the gE gene), and a HSV-1 (strain HSZP)-infected cell extract served as positive controls, and three non-structural recombinant HSV-1 fusion proteins (ICP27, UL9/OBP and thymidine kinase - TK) were used as presumed non-protective (negative) controls. Protection tests showed that the LD 50 value of the challenging infectious virus increased 90-fold in mice immunized with ICP27, but remained unchanged in other control mice immunized with TK and OBP polypeptides. A significant protection (the LD 50 value of challenging virus increased 800-fold) was noted following immunization with gD1/313, while immunization with the gE-del virus and/or the gD1 DNA vaccine resulted in a more than 4,000-fold increase of the challenging virus dose killing 50% of the animals. Using ELISA, elevated antibody titers were detected following immunizations with gD1/313, gE-del virus, and/or HSV-1-infected-cell extract. In addition, all of the three non-structural proteins elicited a good humoral response (with titres ranging from 1:16,000 to 1:128,000). The lowest IgG response (1:8,000) was noted after immunization with the gD1 DNA vaccine. Peripheral blood leukocytes (PBLs) as well as splenocytes from mice immunized with gD1/313, gE-del virus, and gD1-plasmid responded in lymphocyte transformation test (LTT) to the presence of purified gD1/313 antigen. For PBLs, the most significant stimulation of thymidine incorporation was registered at a gD1/313 concentration of 5 µg/100 µl, while the splenocytes from DNA vaccine-immunized mice responded already at a concentration of 1 µg/100 µl.

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