A synthetic human cytomegalovirus pp65-IE1 fusion antigen efficiently induces and expands virus specific T cells
| Autor: | Michael H. Lehmann, Gerd Sutter, Andreas Moosmann, Asisa Volz, Ellen Kathrin Link, Stefanie Ameres, Christine Brandmüller, Yasemin Suezer |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Human cytomegalovirus viruses Genetic Vectors Cytomegalovirus Epitopes T-Lymphocyte Poxviridae Infections Biology complex mixtures Virus Fusion gene 03 medical and health sciences chemistry.chemical_compound Mice Viral Proteins Antigen medicine Animals Humans Antigens Viral Herpesviridae General Veterinary General Immunology and Microbiology Public Health Environmental and Occupational Health virus diseases biochemical phenomena metabolism and nutrition Vector vaccine medicine.disease Fusion protein Virology 030104 developmental biology Infectious Diseases chemistry Cytomegalovirus Infections Molecular Medicine Female Vaccinia Nuclear localization sequence |
| Zdroj: | Vaccine. 35(38) |
| ISSN: | 1873-2518 |
| Popis: | Infection with human cytomegalovirus (HCMV) can cause severe complications in newborns and immunocompromised patients, and a prophylactic or therapeutic vaccine against HCMV is not available. Here, we generated a HCMV vaccine candidate fulfilling the regulatory requirements for GMP-compliant production and clinical testing. A novel synthetic fusion gene consisting of the coding sequences of HCMV pp65 and IE1 having a deleted nuclear localization sequence and STAT2 binding domain was introduced into the genome of the attenuated vaccinia virus strain MVA. This recombinant MVA, MVA-syn65_IE1, allowed for the production of a stable ∼120kDa syn65_IE1 fusion protein upon tissue culture infection. MVA-syn65_IE1 infected CD40-activated B cells activated and expanded pp65- and IE1-specific T cells derived from HCMV-seropositive donors to at least equal levels as control recombinant MVA expressing single genes for pp65 or IE1. Additionally, we show that MVA-syn65_IE1 induced HCMV pp65- and IE1-epitope specific T cells in HLA-A2.1-/HLA-DR1-transgenic H-2 class I-/class II-knockout mice. Thus, MVA-syn65_IE1 represents a promising vaccine candidate against HCMV and constitutes a basis for the generation of a multivalent vaccine targeting relevant pathogens in immunocompromised patients. |
| Databáze: | OpenAIRE |
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