title: Enhanced immunity and protective efficacy against SIVmac251 intrarectal challenge following ad-SIV priming by multiple mucosal routes and gp120 boosting in MPL-SE.
abstract: Previously, 39% of rhesus macaques primed orally, intranasally, and intratracheally with adenovirus (Ad)-simian immunodeficiency virus (SIV) recombinants and boosted with gp120 in monophosphoryl lipid A-stable emulsion (MPL-SE) remained aviremic or cleared or controlled viremia at the threshold of detection following SIV(mac251) intrarectal challenge (Study B). In contrast, no macaques primed orally and intranasally with Ad-SIV recombinants and boosted with gp120 in Quillaja Saponaria-21 exhibited undetectable viremia post-challenge (Study A). We conducted a detailed comparison of the studies to elucidate the effect of different vaccine regimens on induced immunity associated with the different challenge outcomes. Quantitative viral load comparisons were statistically analyzed. All immune responses were assessed at identical timepoints post-immunization, and cellular immunity was re-evaluated on cryopreserved cells from Study B macaques to match Study A data acquired with frozen cells. Study B exhibited greater protective efficacy, increased levels of p11C and p54m tetramer positive cells and a trend toward enhanced interferon-gamma secreting cells in response to Env and Gag peptides, modestly enhanced serum neutralizing antibodies, and greater positivity in anti-gp120 rectal IgA and IgG antibodies. Study A macaques exhibited greater positivity in salivary IgA anti-gp120 antibodies. Thus, the vaccine regimen using oral-intranasal-intratracheal priming and protein boosting in MPL-SE was superior, eliciting greater protective efficacy against pathogenic SIV(mac251) and enhanced SIV-specific immunity, systemically and at rectal sites. The mechanism(s) by which binding antibodies, lacking neutralizing activity against the primary challenge virus, may contribute to protection requires further study.
authors.affiliation: Vaccine Branch, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Pinczewski
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.forename: Nina
authors.initials: N
authors.lastname: Malkevitch
authors.forename: L Jean
authors.initials: LJ
authors.lastname: Patterson
authors.forename: Kristine
authors.initials: K
authors.lastname: Aldrich
authors.forename: W Gregory
authors.initials: WG
authors.lastname: Alvord
authors.forename: Marjorie
authors.initials: M
authors.lastname: Robert-Guroff
mesh_terms: D000256:Adenoviridae / Q000276:immunology; D000276:Adjuvants, Immunologic; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D005260:Female; D018928:Immunity, Mucosal; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000096:biosynthesis; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000276:immunology; D008253:Macaca mulatta; D008297:Male; D008562:Membrane Glycoproteins / Q000008:administration & dosage* / Q000276:immunology; D018449:SAIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology; D012463:Saliva / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage; D014759:Viral Envelope Proteins / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D008050:Lipid A; D008562:Membrane Glycoproteins; D018449:SAIDS Vaccines; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; C069623:gp120 protein, Simian immunodeficiency virus; D007371:Interferon-gamma; C048436:monophosphoryl lipid A