title: Microneedle mediated intradermal delivery of adjuvanted recombinant HIV-1 CN54gp140 effectively primes mucosal boost inoculations.
abstract: Dissolving polymeric microneedle arrays formulated to contain recombinant CN54 HIVgp140 and the TLR4 agonist adjuvant MPLA were assessed for their ability to elicit antigen-specific immunity. Using this novel microneedle system we successfully primed antigen-specific responses that were further boosted by an intranasal mucosal inoculation to elicit significant antigen-specific immunity. This prime-boost modality generated similar serum and mucosal gp140-specific IgG levels to the adjuvanted and systemic subcutaneous inoculations. While the microneedle primed groups demonstrated a balanced Th1/Th2 profile, strong Th2 polarization was observed in the subcutaneous inoculation group, likely due to the high level of IL-5 secretion from cells in this group. Significantly, the animals that received a microneedle prime and intranasal boost regimen elicited a high level IgA response in both the serum and mucosa, which was greatly enhanced over the subcutaneous group. The splenocytes from this inoculation group secreted moderate levels of IL-5 and IL-10 as well as high amounts of IL-2, cytokines known to act in synergy to induce IgA. This work opens up the possibility for microneedle-based HIV vaccination strategies that, once fully developed, will greatly reduce risk for vaccinators and patients, with those in the developing world set to benefit most.
authors.affiliation: School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK.
authors.forename: Aditya
authors.initials: A
authors.lastname: Pattani
authors.forename: Paul F
authors.initials: PF
authors.lastname: McKay
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Garland
authors.forename: Rhonda M
authors.initials: RM
authors.lastname: Curran
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Migalska
authors.forename: Corona M
authors.initials: CM
authors.lastname: Cassidy
authors.forename: R Karl
authors.initials: RK
authors.lastname: Malcolm
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Shattock
authors.forename: Helen O
authors.initials: HO
authors.lastname: McCarthy
authors.forename: Ryan F
authors.initials: RF
authors.lastname: Donnelly
mesh_terms: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000279:Administration, Cutaneous; D000818:Animals; D016207:Cytokines / Q000276:immunology; D005260:Female; D015497:HIV-1; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives*; D051379:Mice; D008807:Mice, Inbred BALB C; D008845:Microinjections; D009339:Needles; D011994:Recombinant Proteins / Q000008:administration & dosage; D013154:Spleen / Q000166:cytology / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000819:agonists; D014621:Vagina / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D016207:Cytokines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008050:Lipid A; D011994:Recombinant Proteins; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1; C048436:monophosphoryl lipid A