Non-propagating, recombinant vesicular stomatitis virus vectors encoding respiratory syncytial virus proteins generate potent humoral and cellular immunity against RSV and are protective in mice.
Autor: | Johnson JE; Pfizer Vaccine Research, 401 North Middletown Road, Pearl River, NY 10965, USA. erik.johnson@pfizer.com, McNeil LK, Megati S, Witko SE, Roopchand VS, Obregon JH, Illenberger DM, Kotash CS, Nowak RM, Braunstein E, Yurgelonis I, Jansen KU, Kalyan NK, Sidhu MK |
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Jazyk: | angličtina |
Zdroj: | Immunology letters [Immunol Lett] 2013 Feb; Vol. 150 (1-2), pp. 134-44. Date of Electronic Publication: 2012 Dec 20. |
DOI: | 10.1016/j.imlet.2012.12.005 |
Abstrakt: | Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract illness in infants, the elderly, and other high-risk individuals. Despite years of research in this field, there is no effective licensed vaccine to prevent RSV infection. We have generated candidate RSV vaccines using a recombinant vesicular stomatitis virus (rVSV) replicon in which the attachment and fusion domains of the VSV glycoprotein (G) have been deleted (rVSV-Gstem), rendering the virus propagation-defective except in the presence of complementing VSV G provided in trans. A form of this vector encoding the RSV fusion protein (F) gene expressed high levels of F in vitro and elicited durable neutralizing antibody responses as well as complete protection against RSV challenge in vivo. Mice vaccinated with rVSV-Gstem-RSV-F replicons also developed robust cellular responses characterized by both primary and memory Th1-biased CD8+ and CD4+ T cells. Furthermore, a single high dose of the Gstem-RSV-F replicon was effective against challenge with both RSV A and B subgroup viruses. Finally, addition of an RSV glycoprotein (G)-expressing Gstem vector significantly improved the incomplete protection achieved with a single low dose of Gstem-RSV-F vector alone. (Copyright © 2012 Elsevier B.V. All rights reserved.) |
Databáze: | MEDLINE |
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