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

作者：Johnson J Erik^*; McNeil Lisa K; Megati Shakuntala; Witko Susan E; Roopchand Vidia S; Obregon Jennifer H; Illenberger Deanne M; Kotash Cheryl S; Nowak Rebecca M; Braunstein Emily; Yurgelonis Irene; Jansen Kathrin U; Kalyan Narender K; Sidhu Maninder K

来源：Immunology Letters, 2013, 150(1-2): 134-144.

DOI：10.1016/j.imlet.2012.12.005

• Vesicular stomatitis virus vectors.
• Respiratory syncytial virus vaccines
• F protein
• Neutralizing antibodies

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.

• 出版日期2013-2