Anti-Metapneumovirus Monoclonal antibody, Clone INQW68

To apply serological testing for human metapneumovirus (hMPV) to large-scale sera samples, an enzyme-linked immunosorbent assay (ELISA) was developed in which purified virions were used as the antigen. The ELISA was evaluated using 102 human sera specimens from patients aged 0-59 years. There was a positive association between the ELISA results and neutralization test titers, with the correlation coefficients being greater in children <6 years old (rho=0.899, P<0.0001), which is consistent with a primary infection, than in persons >= 6 years old (rho=0.523, P<0.0001). Fifty sera samples were subjected to radioimmunoprecipitation to measure the quantity of antibodies to the fusion protein (RIP-F) and the nucleoprotein (RIP-N). The results showed significant associations between the ELISA titers and the amount of RIP-F as determined by radioimmunoprecipitation in children <6 years old (rho = 0.804, P=0.0083) and in persons >= 6 years old (rho=0.577, P = 0.0009). The correlation between the ELISA titer and the amount of RIP-N determined by radioimmunoprecipitation was not significant in persons >= 6 years old (rho=0.417, P=0.0829), although this correlation was significant in children <6 years old (rho=0.764, P=0.0137). The ELISA titer correlated with the amount of antibodies to the F protein, but not to the N protein. This whole virus-based ELISA will be useful for the diagnosis of hMPV infection in clinical laboratories and is also useful for the large-scale investigations, such as seroprevalence among residents of a particular region. (C) 2009 Elsevier B.V. All rights reserved.

Human metapneumovirus (hMPV) is a respiratory virus detected in >= 9% of allogeneic hematopoietic stem cell transplant (HSCT) recipients, in whom it can cause significant morbidity and mortality. Given the lack of effective antivirals, we investigated the potential for immunotherapeutic intervention, using adoptively transferred T cells. Thus, we characterized the cellular immune response to the virus and identified F, N, M2-1, M, and P as immunodominant target antigens. Reactive T cells were polyclonal (ie, they expressed CD4 and CD8), T-helper type 1 polarized, and polyfunctional (ie, they produced interferon gamma, tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, and granzyme B), and they were able to kill autologous antigen-loaded targets. The detection of hMPV-specific T cells in HSCT recipients who endogenously controlled active infections support the clinical importance of T-cell immunity in mediating protective antiviral effects. Our results demonstrate the feasibility of developing an immunotherapy for immunocompromised patients with uncontrolled infections.