title: Viral vectored granulocyte-macrophage colony stimulating factor inhibits vaccine protection in an SIV challenge model: protection correlates with neutralizing antibody.
abstract: In a previous vaccine study, we reported significant and apparently sterilizing immunity to high-dose, mucosal, simian immunodeficiency virus (SIV) quasi-species challenge. The vaccine consisted of vectors based on vesicular stomatitis virus (VSV) expressing simian immunodeficiency virus (SIV) gag and env genes, a boost with propagating replicon particles expressing the same SIV genes, and a second boost with VSV-based vectors. Concurrent with that published study we had a parallel group of macaques given the same doses of vaccine vectors, but in addition, we included a third VSV vector expressing rhesus macaque GM-CSF in the priming immunization only. We report here that addition of the vector expressing GM-CSF did not enhance CD8 T cell or antibody responses to SIV antigens, and almost completely abolished the vaccine protection against high-dose mucosal challenge with SIV. Expression of GM-CSF may have limited vector replication excessively in the macaque model. Our results suggest caution in the use of GM-CSF as a vaccine adjuvant, especially when expressed by a viral vector. Combining vaccine group animals from this study and the previous study we found that there was a marginal but significant positive correlation between the neutralizing antibody to a neutralization resistant SIV Env and protection from infection.
authors.affiliation: Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: John B
authors.initials: JB
authors.lastname: Schell
authors.forename: Kapil
authors.initials: K
authors.lastname: Bahl
authors.forename: Nina F
authors.initials: NF
authors.lastname: Rose
authors.forename: Linda
authors.initials: L
authors.lastname: Buonocore
authors.forename: Meredith
authors.initials: M
authors.lastname: Hunter
authors.forename: Preston A
authors.initials: PA
authors.lastname: Marx
authors.forename: Celia C
authors.initials: CC
authors.lastname: LaBranche
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: John K
authors.initials: JK
authors.lastname: Rose
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D018928:Immunity, Mucosal; D008253:Macaca mulatta; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D018116:Vesiculovirus / Q000235:genetics
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D018449:SAIDS Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor