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An Interleukin 12 Adjuvanted Herpes Simplex Virus 2 DNA Vaccine Is More Protective Than a Glycoprotein D Subunit Vaccine in a High-Dose Murine Challenge Model
- Source :
- Viral Immunology. 30:178-195
- Publication Year :
- 2017
- Publisher :
- Mary Ann Liebert Inc, 2017.
-
Abstract
- Vaccination is a proven intervention against human viral diseases; however, success against Herpes Simplex Virus 2 (HSV-2) remains elusive. Most HSV-2 vaccines tested in humans to date contained just one or two immunogens, such as the virion attachment receptor glycoprotein D (gD) and/or the envelope fusion protein, glycoprotein B (gB). At least three factors may have contributed to the failures of subunit-based HSV-2 vaccines. First, immune responses directed against one or two viral antigens may lack sufficient antigenic breadth for efficacy. Second, the antibody responses elicited by these vaccines may have lacked necessary Fc-mediated effector functions. Third, these subunit vaccines may not have generated necessary protective cellular immune responses. We hypothesized that a polyvalent combination of HSV-2 antigens expressed from a DNA vaccine with an adjuvant that polarizes immune responses toward a T helper 1 (Th1) phenotype would compose a more effective vaccine. We demonstrate that delivery of DNA expressing full-length HSV-2 glycoprotein immunogens by electroporation with the adjuvant interleukin 12 (IL-12) generates substantially greater protection against a high-dose HSV-2 vaginal challenge than a recombinant gD subunit vaccine adjuvanted with alum and monophosphoryl lipid A (MPL). Our results further show that DNA vaccines targeting optimal combinations of surface glycoproteins provide better protection than gD alone and provide similar survival benefits and disease symptom reductions compared with a potent live attenuated HSV-2 0ΔNLS vaccine, but that mice vaccinated with HSV-2 0ΔNLS clear the virus much faster. Together, our data indicate that adjuvanted multivalent DNA vaccines hold promise for an effective HSV-2 vaccine, but that further improvements may be required.
- Subjects :
- 0301 basic medicine
Herpesvirus 2, Human
viruses
medicine.medical_treatment
Protein subunit
Immunology
Herpesvirus Vaccines
Biology
medicine.disease_cause
Virus
DNA vaccination
Mice
03 medical and health sciences
Immune system
Adjuvants, Immunologic
Antigen
Virology
Vaccines, DNA
medicine
Animals
Glycoproteins
Vaccines, Synthetic
Herpes Genitalis
Membrane Proteins
Interleukin-12
Survival Analysis
Vaccination
Disease Models, Animal
Treatment Outcome
030104 developmental biology
Herpes simplex virus
Vaccines, Subunit
Molecular Medicine
Adjuvant
Subjects
Details
- ISSN :
- 15578976 and 08828245
- Volume :
- 30
- Database :
- OpenAIRE
- Journal :
- Viral Immunology
- Accession number :
- edsair.doi.dedup.....ffc79a551197637892d37f53c12a0dfc