Rsv Proteins - Roles in Host Immunity and Immunoprophylaxis

Collins, P L.

Abstract

We are investigating approaches for utilizing recombinant DNA techniques in developing a vaccine for human respiratory syncytial virus (RSV). Previously, vaccinia virus recombinants that express individually the RSV F and G glycoproteins were shown to be highly immunogenic and effective in inducing resistance to challenge RSV infection in rodents and non-human primates. Analogous recombinants are being constructed with vaccinia virus strains (Wyeth and Lister) that are acceptable for sue in humans. Vaccinia virus recombinants also have been constructed with seven other RSV genes, namely the 1C, 1B,N, P, M 22K and 1A genes. Expression of the authentic RSV protein has been confirmed in each case, and these recombinants are being used to evaluate possible roles for these proteins in host immunity and virus-induced pathology. Two different adenovirus type 5 recombinants that contain the RSV F gene under the control of adenovirus promoters have been constructed, and these are being analyzed to determine whether the F protein is synthesized and processed authentically in recombinant-infected cells. Recombinant baculoviruses that express individually the F and G proteins are being evaluated as a potential source of purified F and G protein for a non-replicating subunit vaccine.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Intramural Research (Z01)
• Project #: 1Z01AI000372-06
• Application #: 3818214
• Support Year: 6
• Fiscal Year: 1988

Institution

• Name: Niaid Extramural Activities
• Country: United States

Publications

Buchholz, Ursula J; Ward, Jerrold M; Lamirande, Elaine W et al. (2009) Deletion of nonstructural proteins NS1 and NS2 from pneumonia virus of mice attenuates viral replication and reduces pulmonary cytokine expression and disease. J Virol 83:1969-80

Collins, Peter L; Graham, Barney S (2008) Viral and host factors in human respiratory syncytial virus pathogenesis. J Virol 82:2040-55

Munir, Shirin; Le Nouen, Cyril; Luongo, Cindy et al. (2008) Nonstructural proteins 1 and 2 of respiratory syncytial virus suppress maturation of human dendritic cells. J Virol 82:8780-96

Chapman, Joanna; Abbott, Elizabeth; Alber, Dagmar G et al. (2007) RSV604, a novel inhibitor of respiratory syncytial virus replication. Antimicrob Agents Chemother 51:3346-53

Krempl, Christine D; Wnekowicz, Anna; Lamirande, Elaine W et al. (2007) Identification of a novel virulence factor in recombinant pneumonia virus of mice. J Virol 81:9490-501

Vallbracht, Simone; Jessen, Birthe; Mrusek, Sonja et al. (2007) Influence of a single viral epitope on T cell response and disease after infection of mice with respiratory syncytial virus. J Immunol 179:8264-73

Harker, James; Bukreyev, Alexander; Collins, Peter L et al. (2007) Virally delivered cytokines alter the immune response to future lung infections. J Virol 81:13105-11

Chi, Bo; Dickensheets, Harold L; Spann, Kirsten M et al. (2006) Alpha and lambda interferon together mediate suppression of CD4 T cells induced by respiratory syncytial virus. J Virol 80:5032-40

Bukreyev, Alexander; Serra, Maria Elina; Laham, Federico R et al. (2006) The cysteine-rich region and secreted form of the attachment G glycoprotein of respiratory syncytial virus enhance the cytotoxic T-lymphocyte response despite lacking major histocompatibility complex class I-restricted epitopes. J Virol 80:5854-61

Kotelkin, Alexander; Belyakov, Igor M; Yang, Lijuan et al. (2006) The NS2 protein of human respiratory syncytial virus suppresses the cytotoxic T-cell response as a consequence of suppressing the type I interferon response. J Virol 80:5958-67