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

Aditya Pattani, Paul F McKay, Martin J Garland, Rhonda M Curran, Katarzyna Migalska, Corona M Cassidy, R Karl Malcolm, Robin J Shattock, Helen O McCarthy, Ryan F Donnelly

    Research output: Contribution to journalArticle

    35 Citations (Scopus)

    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.
    LanguageEnglish
    JournalJournal of Controlled Release
    Volumex
    DOIs
    Publication statusPublished - 7 Aug 2012

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    HIV-1
    Interleukin-5
    Antigens
    Immunoglobulin A
    Immunity
    Serum
    Interleukin-10
    Interleukin-2
    Mucous Membrane
    Vaccination
    Immunoglobulin G
    HIV
    Cytokines
    GP 140

    Cite this

    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. / Microneedle mediated intradermal delivery of adjuvanted recombinant HIV-1 CN54gp140 effectively primes mucosal boost inoculations. In: Journal of Controlled Release. 2012 ; Vol. x.
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    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.",
    author = "Aditya Pattani and McKay, {Paul F} and Garland, {Martin J} and Curran, {Rhonda M} and Katarzyna Migalska and Cassidy, {Corona M} and Malcolm, {R Karl} and Shattock, {Robin J} and McCarthy, {Helen O} and Donnelly, {Ryan F}",
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    Pattani, A, McKay, PF, Garland, MJ, Curran, RM, Migalska, K, Cassidy, CM, Malcolm, RK, Shattock, RJ, McCarthy, HO & Donnelly, RF 2012, 'Microneedle mediated intradermal delivery of adjuvanted recombinant HIV-1 CN54gp140 effectively primes mucosal boost inoculations', Journal of Controlled Release, vol. x. https://doi.org/10.1016/j.jconrel.2012.07.039

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

    In: Journal of Controlled Release, Vol. x, 07.08.2012.

    Research output: Contribution to journalArticle

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    AU - Pattani, Aditya

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    AU - Garland, Martin J

    AU - Curran, Rhonda M

    AU - Migalska, Katarzyna

    AU - Cassidy, Corona M

    AU - Malcolm, R Karl

    AU - Shattock, Robin J

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    AU - Donnelly, Ryan F

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    N2 - 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.

    AB - 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.

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