Herpes Simplex Virus Type 2 Is More Difficult to Neutralize by Antibodies Than Herpes Simplex Virus Type 1
Infections with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are a global health burden. Besides painful oral or genital lesions in otherwise healthy subjects, both viruses can cause devastating morbidity and mortality in immune-compromised and immune-immature individuals. The latter are p...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-08-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/8/3/478 |
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| author | Christiane Silke Heilingloh Christopher Lull Elissa Kleiser Mira Alt Leonie Schipper Oliver Witzke Mirko Trilling Anna-Maria Eis-Hübinger Ulf Dittmer Adalbert Krawczyk |
| author_facet | Christiane Silke Heilingloh Christopher Lull Elissa Kleiser Mira Alt Leonie Schipper Oliver Witzke Mirko Trilling Anna-Maria Eis-Hübinger Ulf Dittmer Adalbert Krawczyk |
| author_sort | Christiane Silke Heilingloh |
| collection | DOAJ |
| description | Infections with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are a global health burden. Besides painful oral or genital lesions in otherwise healthy subjects, both viruses can cause devastating morbidity and mortality in immune-compromised and immune-immature individuals. The latter are particularly susceptible to a disseminated, life-threatening disease. Neutralizing antibodies (NAb) constitute a correlate of protection from disease, and are promising candidates for the prophylactic or therapeutic treatment of severe HSV infections. However, a clinical vaccine trial suggested that HSV-2 might be more resistant to NAbs than HSV-1. In the present study, we investigated the antiviral efficacy of the well-characterized humanized monoclonal antibody (mAb) hu2c against HSV-2, in a NOD/SCID immunodeficiency mouse model. Despite the fact that hu2c recognizes a fully conserved epitope and binds HSV-1 and HSV-2 glycoprotein B with equal affinity, it was much less effective against HSV-2 in vitro and in NOD/SCID mice. Although intravenous antibody treatment prolonged the survival of HSV-2-infected mice, complete protection from death was not achieved. Our data demonstrate that HSV-2 is more resistant to NAbs than HSV-1, even if the same antibody and antigen are concerned, making the development of a vaccine or therapeutic antibodies more challenging. |
| first_indexed | 2024-03-10T16:46:33Z |
| format | Article |
| id | doaj.art-170f18424ec64b1ab6e2cfa987ee18f9 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T16:46:33Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-170f18424ec64b1ab6e2cfa987ee18f92023-11-20T11:31:39ZengMDPI AGVaccines2076-393X2020-08-018347810.3390/vaccines8030478Herpes Simplex Virus Type 2 Is More Difficult to Neutralize by Antibodies Than Herpes Simplex Virus Type 1Christiane Silke Heilingloh0Christopher Lull1Elissa Kleiser2Mira Alt3Leonie Schipper4Oliver Witzke5Mirko Trilling6Anna-Maria Eis-Hübinger7Ulf Dittmer8Adalbert Krawczyk9Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen, GermanyDepartment of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen, GermanyBiopharmaceuticals QC Services, Virology & Contamination Detection, Boehringer Ingelheim, D-55216 Biberach, GermanyDepartment of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen, GermanyDepartment of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen, GermanyDepartment of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen, GermanyInstitute for Virology, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen, GermanyInstitute of Virology, Medical Faculty, University of Bonn, D-53113 Bonn, GermanyInstitute for Virology, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen, GermanyDepartment of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen, GermanyInfections with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are a global health burden. Besides painful oral or genital lesions in otherwise healthy subjects, both viruses can cause devastating morbidity and mortality in immune-compromised and immune-immature individuals. The latter are particularly susceptible to a disseminated, life-threatening disease. Neutralizing antibodies (NAb) constitute a correlate of protection from disease, and are promising candidates for the prophylactic or therapeutic treatment of severe HSV infections. However, a clinical vaccine trial suggested that HSV-2 might be more resistant to NAbs than HSV-1. In the present study, we investigated the antiviral efficacy of the well-characterized humanized monoclonal antibody (mAb) hu2c against HSV-2, in a NOD/SCID immunodeficiency mouse model. Despite the fact that hu2c recognizes a fully conserved epitope and binds HSV-1 and HSV-2 glycoprotein B with equal affinity, it was much less effective against HSV-2 in vitro and in NOD/SCID mice. Although intravenous antibody treatment prolonged the survival of HSV-2-infected mice, complete protection from death was not achieved. Our data demonstrate that HSV-2 is more resistant to NAbs than HSV-1, even if the same antibody and antigen are concerned, making the development of a vaccine or therapeutic antibodies more challenging.https://www.mdpi.com/2076-393X/8/3/478HSV-1HSV-2neutralizing antibodies |
| spellingShingle | Christiane Silke Heilingloh Christopher Lull Elissa Kleiser Mira Alt Leonie Schipper Oliver Witzke Mirko Trilling Anna-Maria Eis-Hübinger Ulf Dittmer Adalbert Krawczyk Herpes Simplex Virus Type 2 Is More Difficult to Neutralize by Antibodies Than Herpes Simplex Virus Type 1 Vaccines HSV-1 HSV-2 neutralizing antibodies |
| title | Herpes Simplex Virus Type 2 Is More Difficult to Neutralize by Antibodies Than Herpes Simplex Virus Type 1 |
| title_full | Herpes Simplex Virus Type 2 Is More Difficult to Neutralize by Antibodies Than Herpes Simplex Virus Type 1 |
| title_fullStr | Herpes Simplex Virus Type 2 Is More Difficult to Neutralize by Antibodies Than Herpes Simplex Virus Type 1 |
| title_full_unstemmed | Herpes Simplex Virus Type 2 Is More Difficult to Neutralize by Antibodies Than Herpes Simplex Virus Type 1 |
| title_short | Herpes Simplex Virus Type 2 Is More Difficult to Neutralize by Antibodies Than Herpes Simplex Virus Type 1 |
| title_sort | herpes simplex virus type 2 is more difficult to neutralize by antibodies than herpes simplex virus type 1 |
| topic | HSV-1 HSV-2 neutralizing antibodies |
| url | https://www.mdpi.com/2076-393X/8/3/478 |
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