Vaccination with the Secreted Glycoprotein G of Herpes Simplex Virus 2 Induces Protective Immunity after Genital Infection.
Herpes simplex virus 2 (HSV-2) infects the genital mucosa and establishes a life-long infection in sensory ganglia. After primary infection HSV-2 may reactivate causing recurrent genital ulcerations. HSV-2 infection is prevalent, and globally more than 400 million individuals are infected. As clinical trials have failed to show protection against HSV-2 infection, new vaccine candidates are warranted. The secreted glycoprotein G (sgG-2) of HSV-2 was evaluated as a prophylactic vaccine in mice using two different immunization and adjuvant protocols. The protocol with three intramuscular immunizations combining sgG-2 with cytosine-phosphate-guanine dinucleotide (CpG) motifs and alum induced almost complete protection from genital and systemic disease after intra-vaginal challenge with HSV-2. Robust immunoglobulin G (IgG) antibody titers were detected with no neutralization activity. Purified splenic CD4+ T cells proliferated and produced interferon-γ (IFN-γ) when re-stimulated with the antigen in vitro. sgG-2 + adjuvant intra-muscularly immunized mice showed a significant reduction of infectious HSV-2 and increased IFN-γ levels in vaginal washes. The HSV-2 DNA copy numbers were significantly reduced in dorsal root ganglia, spinal cord, and in serum at day six or day 21 post challenge. We show that a sgG-2 based vaccine is highly effective and can be considered as a novel candidate in the development of a prophylactic vaccine against HSV-2 infection.
Section of Virology, Department of Infectious Medicine, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Guldhedsgatan 10 B, S-413 46 Gothenburg, Sweden. karin.onnheim@gu.se.
Karin
K
Önnheim
Section of Virology, Department of Infectious Medicine, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Guldhedsgatan 10 B, S-413 46 Gothenburg, Sweden. maria_ekblad@hotmail.com.
Maria
M
Ekblad
Section of Virology, Department of Infectious Medicine, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Guldhedsgatan 10 B, S-413 46 Gothenburg, Sweden. staffan.gorander@gu.se.
Staffan
S
Görander
Section of Virology, Department of Infectious Medicine, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Guldhedsgatan 10 B, S-413 46 Gothenburg, Sweden. tomas.bergstrom@gu.se.
Tomas
T
Bergström
Section of Virology, Department of Infectious Medicine, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Guldhedsgatan 10 B, S-413 46 Gothenburg, Sweden. jan-ake.liljeqvist@gu.se.
Jan-Åke
JÅ
Liljeqvist
D000276:Adjuvants, Immunologic; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D002460:Cell Line; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D005260:Female; D006023:Glycoproteins / Q000008:administration & dosage / Q000276:immunology*; D006558:Herpes Genitalis / Q000517:prevention & control* / Q000821:virology; D022301:Herpes Simplex Virus Vaccines / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019562:Viral Load; D014764:Viral Proteins / Q000008:administration & dosage / Q000276:immunology*
D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D006023:Glycoproteins; D022301:Herpes Simplex Virus Vaccines; C527357:US4 protein, human herpesvirus 2; D014764:Viral Proteins; D007371:Interferon-gamma
herpes simplex virus 2; secreted glycoprotein G; vaccination