title: Prevention of infection by a granulocyte-macrophage colony-stimulating factor co-expressing DNA/modified vaccinia Ankara simian immunodeficiency virus vaccine.
abstract: A simian immunodeficiency virus (SIV) vaccine coexpressing granulocyte-macrophage colony stimulating factor (GM-CSF) prevented infection in 71% of macaques that received 12 rectal challenges. The SIVsmE660 challenge had the tropism of incident human immunodeficiency virus (HIV) infections and a similar genetic distance from the SIV239 vaccine as intraclade HIV isolates. The heterologous prime-boost vaccine regimen used recombinant DNA for priming and recombinant modified vaccinia Ankara for boosting. Co-expression of GM-CSF in the DNA prime enhanced the avidity of elicited immunoglobulin G for SIV envelope glycoproteins, the titers of neutralizing antibody for easy-to-neutralize SIV isolates, and antibody-dependent cellular cytotoxicity. Impressively, the co-expressed GM-CSF increased vaccine-induced prevention of infection from 25% in the non-GM-CSF co-expressing vaccine group to 71% in the GM-CSF co-expressing vaccine group. The prevention of infection showed a strong correlation with the avidity of the elicited Env-specific antibody for the Env of the SIVsmE660 challenge virus (r = 0.9; P < .0001).
authors.affiliation: Yerkes National Primate Research Center, USA.
authors.forename: Lilin
authors.initials: L
authors.lastname: Lai
authors.forename: Suefen
authors.initials: S
authors.lastname: Kwa
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Kozlowski
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.forename: Welkin E
authors.initials: WE
authors.lastname: Johnson
authors.forename: Vanessa
authors.initials: V
authors.lastname: Hirsch
authors.forename: Francois
authors.initials: F
authors.lastname: Villinger
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Chennareddi
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Earl
authors.forename: Bernard
authors.initials: B
authors.lastname: Moss
authors.forename: Rama Rao
authors.initials: RR
authors.lastname: Amara
authors.forename: Harriet L
authors.initials: HL
authors.lastname: Robinson
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D003601:Cytotoxicity Tests, Immunologic; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology*; D007117:Immunization, Secondary / Q000379:methods; D008253:Macaca mulatta; D008297:Male; D009500:Neutralization Tests; D018449:SAIDS Vaccines / Q000235:genetics / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000472:pathogenicity; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D018449:SAIDS Vaccines; D019444:Vaccines, DNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor