Novel HLA-A2-restricted human metapneumovirus epitopes reduce viral titers in mice and are recognized by human T cells

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• 作者：Andrew K. Hastings^a ; Pavlo Gilchuk^a ; Sebastian Joyce^a ; ^b ; John V. Williams^c ; ^{jvw@chp.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Human metapneumovirus ; Paramyxovirus ; Vaccine ; T cell response ; Respiratory infections
• 刊名：Vaccine
• 出版年：2016
• 出版时间：23 May 2016
• 年：2016
• 卷：34
• 期：24
• 页码：2663-2670
• 全文大小：1671 K

文摘

Human metapneumovirus (HMPV) is a major cause of morbidity and mortality from acute lower respiratory tract illness, with most individuals seropositive by age five. Despite the presence of neutralizing antibodies, secondary infections are common and can be severe in young, elderly, and immunocompromised persons. Preclinical vaccine studies for HMPV have suggested a need for a balanced antibody and T cell immune response to enhance protection and avoid lung immunopathology. We infected transgenic mice expressing human HLA-A*0201 with HMPV and used ELISPOT to screen overlapping and predicted epitope peptides. We identified six novel HLA-A2 restricted CD8⁺ T cell (T_CD8) epitopes, with M_39–47 (M39) immunodominant. Tetramer staining detected M39-specific T_CD8 in lungs and spleen of HMPV-immune mice. Immunization with adjuvant-formulated M39 peptide reduced lung virus titers upon challenge. Finally, we show that T_CD8 from HLA-A*0201 positive humans recognize M39 by IFNγ ELISPOT and tetramer staining. These results will facilitate HMPV vaccine development and human studies.