The overall goal of this proposal is to continue development of VSV vectors as AIDS vaccines using the relatively inexpensive mouse and guinea pig models for preliminary evaluation of immune responses. We will continue to evaluate new strategies for increasing memory CTL responses as well as broadly neutralizing antibody responses. Special emphasis will be placed on developing strategies that can induce memory CDS T cells in the absence of CD4 T-cell help. Promising new strategies will be evaluated later in non-human primates under other funding.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI040357-17
Application #
8204849
Study Section
Special Emphasis Panel (NSS)
Program Officer
Warren, Jon T
Project Start
1996-07-15
Project End
2013-12-31
Budget Start
2012-01-01
Budget End
2013-12-31
Support Year
17
Fiscal Year
2012
Total Cost
$324,413
Indirect Cost
$128,393
Name
Yale University
Department
Pathology
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Schell, John B; Bahl, Kapil; Rose, Nina F et al. (2012) Viral vectored granulocyte-macrophage colony stimulating factor inhibits vaccine protection in an SIV challenge model: protection correlates with neutralizing antibody. Vaccine 30:4233-9
Schell, John B; Rose, Nina F; Bahl, Kapil et al. (2011) Significant protection against high-dose simian immunodeficiency virus challenge conferred by a new prime-boost vaccine regimen. J Virol 85:5764-72
Schell, John; Rose, Nina F; Fazo, Nicole et al. (2009) Long-term vaccine protection from AIDS and clearance of viral DNA following SHIV89.6P challenge. Vaccine 27:979-86
Rose, Nina F; Publicover, Jean; Chattopadhyay, Anasuya et al. (2008) Hybrid alphavirus-rhabdovirus propagating replicon particles are versatile and potent vaccine vectors. Proc Natl Acad Sci U S A 105:5839-43
Ramsburg, Elizabeth A; Publicover, Jean M; Coppock, Dagan et al. (2007) Requirement for CD4 T cell help in maintenance of memory CD8 T cell responses is epitope dependent. J Immunol 178:6350-8
Simon, Ian D; Publicover, Jean; Rose, John K (2007) Replication and propagation of attenuated vesicular stomatitis virus vectors in vivo: vector spread correlates with induction of immune responses and persistence of genomic RNA. J Virol 81:2078-82
Publicover, Jean; Ramsburg, Elizabeth; Robek, Michael et al. (2006) Rapid pathogenesis induced by a vesicular stomatitis virus matrix protein mutant: viral pathogenesis is linked to induction of tumor necrosis factor alpha. J Virol 80:7028-36
Publicover, Jean; Ramsburg, Elizabeth; Rose, John K (2005) A single-cycle vaccine vector based on vesicular stomatitis virus can induce immune responses comparable to those generated by a replication-competent vector. J Virol 79:13231-8
Ramsburg, Elizabeth; Publicover, Jean; Buonocore, Linda et al. (2005) A vesicular stomatitis virus recombinant expressing granulocyte-macrophage colony-stimulating factor induces enhanced T-cell responses and is highly attenuated for replication in animals. J Virol 79:15043-53
Schlehuber, Lisa D; Rose, John K (2004) Prediction and identification of a permissive epitope insertion site in the vesicular stomatitis virus glycoprotein. J Virol 78:5079-87

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