title: Reduced MyD88 dependency of ISCOMATRIX™ adjuvant in a DNA prime-protein boost HIV vaccine.
abstract: ISCOMATRIX™ adjuvant is an integrated adjuvant system due to its ability to both facilitate antigen delivery and immunomodulate the innate and adaptive immune responses to vaccination. ISCOMATRIX™ adjuvant strongly induces both humoral and cell-mediated immunity in formulation with a range of antigens in pre-clinical and clinical evaluations. In this study, we describe the adaptive and innate immune responses associated with ISCOMATRIX™ adjuvant in the context of a previously described HIV-1 vaccine, DP6-001. The DP6-001 vaccine consists of a unique pentavalent HIV-1 Env DNA prime-protein boost regimen. This study demonstrates the potent induction of vaccine-specific antibodies in a mouse model, as well as broadly neutralizing antibodies in immunized rabbits. In addition, we identify a potentially critical role for DNA priming in the induction of the vaccine-specific immune response as well as the serum cytokine profiles associated with ISCOMATRIX™ adjuvant. Most interestingly, DNA prime immunizations made ISCOMATRIX™ adjuvant less dependent on the central innate immune adaptor MyD88, revealing a previously unknown mechanism that may expand our knowledge on the use of adjuvants.
authors: Department of Medicine; University of Massachusetts Medical School; Worcester, MA USA.
authors: Rachel
authors: R
authors: Buglione-Corbett
authors: Department of Medicine; Division of Infectious Diseases and Immunology; University of Massachusetts Medical School; Worcester, MA USA.
authors: Kimberly
authors: K
authors: Pouliot
authors: Department of Medicine; Division of Infectious Diseases and Immunology; University of Massachusetts Medical School; Worcester, MA USA.
authors: Robyn
authors: R
authors: Marty-Roix
authors: Department of Medicine; University of Massachusetts Medical School; Worcester, MA USA.
authors: Wei
authors: W
authors: Li
authors: Department of Medicine; University of Massachusetts Medical School; Worcester, MA USA.
authors: Kim
authors: K
authors: West
authors: Department of Medicine; University of Massachusetts Medical School; Worcester, MA USA.
authors: Shixia
authors: S
authors: Wang
authors: CSL Limited, Parkville, VIC Australia.
authors: Adriana Baz
authors: AB
authors: Morelli
authors: Department of Medicine; Division of Infectious Diseases and Immunology; University of Massachusetts Medical School; Worcester, MA USA.
authors: Egil
authors: E
authors: Lien
authors: Department of Medicine; University of Massachusetts Medical School; Worcester, MA USA.
authors: Shan
authors: S
authors: Lu
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D002784:Cholesterol / Q000008:administration & dosage*; D016207:Cytokines / Q000097:blood; D004338:Drug Combinations; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D015497:HIV-1 / Q000276:immunology; D007114:Immunization / Q000379:methods*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D010743:Phospholipids / Q000008:administration & dosage*; D011817:Rabbits; D012503:Saponins / Q000008:administration & dosage*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D016207:Cytokines; D004338:Drug Combinations; D015483:HIV Antibodies; C493786:ISCOMATRIX; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D010743:Phospholipids; D012503:Saponins; D019444:Vaccines, DNA; D022223:Vaccines, Subunit; D002784:Cholesterol
keywords: Al(OH)3; HIV-1; ISCOMATRIX™; MyD88; adjuvants; antibody; cytokines; prime-boost