Microneedle mediated intradermal delivery of adjuvanted recombinant HIV-1 CN54gp140 effectively primes mucosal boost inoculations

• Published in: Journal of controlled release Vol. 162; no. 3; pp. 529 - 537
• Main Authors: Pattani, Aditya, McKay, Paul F., Garland, Martin J., Curran, Rhonda M., Migalska, Katarzyna, Cassidy, Corona M., Malcolm, R. Karl, Shattock, Robin J., McCarthy, Helen O., Donnelly, Ryan F.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 28.09.2012; Elsevier; Elsevier Science Publishers
• Subjects: Adjuvants, Immunologic - administration & dosage; Administration, Cutaneous; agonists; AIDS Vaccines; Animals; Biological and medical sciences; blood serum; Cytokines - immunology; env Gene Products, Human Immunodeficiency Virus - administration & dosage; env Gene Products, Human Immunodeficiency Virus - immunology; Female; General pharmacology; HIV; HIV-1; Human immunodeficiency virus 1; immunity; immunoglobulin A; Immunoglobulin A - blood; Immunoglobulin A - immunology; immunoglobulin G; Immunoglobulin G - blood; Immunoglobulin G - immunology; interleukin-10; interleukin-2; interleukin-5; Intranasal; Lipid A - administration & dosage; Lipid A - analogs & derivatives; Medical sciences; Mice; Mice, Inbred BALB C; Microinjections; Microneedle; mucosa; Needles; patients; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Recombinant Proteins - administration & dosage; risk; secretion; Spleen - cytology; Spleen - immunology; splenocytes; Subcutaneous; Toll-like receptor 4; Toll-Like Receptor 4 - agonists; Vaccination; Vagina - immunology; HIV; Intranasal; Subcutaneous; Vaccination; Microneedle; Delivery system; Immunopathology; Pharmaceutical technology; HIV-1 virus; Retroviridae; AIDS; Intradermal administration; Intranasal administration; Immune deficiency; Lentivirus; Infection; Virus; Viral disease; Subcutaneous administration; Adjuvant; Human immunodeficiency virus
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2012.07.039

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. [Display omitted]