Single and Combination Herpes Simplex Virus Type 2 Glycoprotein Vaccines Adjuvanted with CpG Oligodeoxynucleotides or Monophosphoryl Lipid A Exhibit Differential Immunity That Is Not Correlated to Protection in Animal Models
| العنوان: | Single and Combination Herpes Simplex Virus Type 2 Glycoprotein Vaccines Adjuvanted with CpG Oligodeoxynucleotides or Monophosphoryl Lipid A Exhibit Differential Immunity That Is Not Correlated to Protection in Animal Models |
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| المؤلفون: | Paul Wright, Peter T. Loudon, Susanne Lang, Tim J. Townend, Helen Bright, Jim E. Eyles, Michael J. McCluskie, Katrina Gore, Debbie Chappell, Daisy Hammond, Clare Christy, Paul Cockle, Dana M. Evans, Kate West, Tansi Khodai |
| المصدر: | Clinical and Vaccine Immunology. 18:1702-1709 |
| بيانات النشر: | American Society for Microbiology, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Microbiology (medical), CpG Oligodeoxynucleotide, Herpesvirus 2, Human, T-Lymphocytes, medicine.medical_treatment, Guinea Pigs, Clinical Biochemistry, Immunology, Monophosphoryl Lipid A, Herpesvirus Vaccines, Biology, Antibodies, Viral, Severity of Illness Index, Interferon-gamma, Mice, chemistry.chemical_compound, Immune system, Adjuvants, Immunologic, Viral Envelope Proteins, Immunity, medicine, Animals, Immunology and Allergy, Neutralizing antibody, Herpes Genitalis, Alum, Vaccine Research, Antibodies, Neutralizing, Virology, Disease Models, Animal, Lipid A, Oligodeoxyribonucleotides, CpG site, chemistry, biology.protein, Alum Compounds, Adjuvant |
| الوصف: | Despite several attempts to develop an effective prophylactic vaccine for HSV-2, all have failed to show efficacy in the clinic. The most recent of these failures was the GlaxoSmithKline (GSK) subunit vaccine based on the glycoprotein gD with the adjuvant monophosphoryl lipid A (MPL). In a phase 3 clinical trial, this vaccine failed to protect from HSV-2 disease, even though good neutralizing antibody responses were elicited. We aimed to develop a superior, novel HSV-2 vaccine containing either gD or gB alone or in combination, together with the potent adjuvant CpG oligodeoxynucleotides (CPG). The immunogenic properties of these vaccines were compared in mice. We show that gB/CPG/alum elicited a neutralizing antibody response similar to that elicited by gD/CPG/alum vaccine but a significantly greater gamma interferon (IFN-γ) T cell response. Furthermore, the combined gB-gD/CPG/alum vaccine elicited significantly greater neutralizing antibody and T cell responses than gD/MPL/alum. The efficacies of these candidate vaccines were compared in the mouse and guinea pig disease models, including a novel male guinea pig genital disease model. These studies demonstrated that increased immune response did not correlate to improved protection. First, despite a lower IFN-γ T cell response, the gD/CPG/alum vaccine was more effective than gB/CPG/alum in mice. Furthermore, the gB-gD/CPG/alum vaccine was no more effective than gD/MPL/alum in mice or male guinea pigs. We conclude that difficulties in correlating immune responses to efficacy in animal models will act as a deterrent to researchers attempting to develop effective HSV vaccines. |
| تدمد: | 1556-679X 1556-6811 |
| DOI: | 10.1128/cvi.05071-11 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9691b2ab6a04fd1551cdec6f0ad04204 https://doi.org/10.1128/cvi.05071-11 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9691b2ab6a04fd1551cdec6f0ad04204 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1556679X 15566811 |
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| DOI: | 10.1128/cvi.05071-11 |