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

Aditya Pattani, Paul F McKay, Ryan F Donnelly, Martin J Garland, K Migalska, CM Cassidy, R Karl Malcolm, Robin J Shattock, Rhonda M Curran

    Research output: Contribution to journalArticle

    Abstract

    Background: Microneedles have previously been shown to enhance transdermal delivery of drugs and macromolecules. Their ability to effectively penetrate the dermis over a relatively large surface area offers potential use as minimally-invasive and painless replacements for more conventional parenteral vaccine regimens. In this study we compared the immune responses to HIV CN54gp140 using microneedles alone or a microneedle prime followed by mucosal boosting with monophosphoryl lipid A adjuvanted protein.Methods: Polymeric microneedle arrays that dissolve after piercing the skin were fabricated from poly(methylvinylether/ maleic acid) (Gantrez AN139) using laser-engineered siliconemicromould templates. Three groups of 8 BALB/c mice were primed using microneedles containing CN54gp140 and monophosphoryl lipid A. Three boosts were performed at two week intervals, using either the same microneedle formulation or vaginal or nasal administration of an antigen/adjuvant solution. Another group received four subcutaneous immunisations. Mice were sampled (serum and vaginal wash) prior to each vaccinationand two weeks post final immunization. Antigen-specific IgG and IgA production was assessed in the sera and mucosal lavage samples by quantitative ELISA. Splenocytes were harvested at necropsy and analysed for lymphocyte proliferation.Results: CN54gp140-specific serum IgG and lymphocyte proliferation responses were elicited in the subcutaneous immunization group and in those animals that were primed using microneedle delivery and boosted mucosally via the nasal route. Only the microneedle prime / intranasal boost group mounted a robust IgA response. In this group, IgG1 and IgG2a subtype quantification revealed a strong bias toward IgG2a.Conclusion: We have demonstrated that using a novel microneedle device to prime immunity followed by an intranasal boost elicits significant antigen-specific immune responses. This regimen generated similar serum IgG levels to the subcutaneous inoculations, but in contrast IgA was significantly elevated. This vaccination modality also induced a strong bias toward the IgG2a subtype suggesting a Th1 skewing of the immune response phenotype.
    LanguageEnglish
    JournalAIDS Research and Human Retroviruses
    Volume27
    Issue number10
    DOIs
    Publication statusPublished - 2011

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    HIV-1
    Immunoglobulin G
    Immunoglobulin A
    Immunization
    Serum
    Intravaginal Administration
    Lymphocytes
    Antigens
    Intranasal Administration
    Therapeutic Irrigation
    Histocompatibility Antigens Class II
    Dermis
    Nose
    Immunity
    Vaccination
    Lasers
    Vaccines
    Enzyme-Linked Immunosorbent Assay
    HIV
    Phenotype

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    Pattani, Aditya ; McKay, Paul F ; Donnelly, Ryan F ; Garland, Martin J ; Migalska, K ; Cassidy, CM ; Malcolm, R Karl ; Shattock, Robin J ; Curran, Rhonda M. / Microneedle mediated intradermal delivery of adjuvanted recombinant HIV-1 CN54gp140 effectively primes mucosal boost inoculations. In: AIDS Research and Human Retroviruses. 2011 ; Vol. 27, No. 10.
    @article{316b0ee298474221a84a93d4de95b1c8,
    title = "Microneedle mediated intradermal delivery of adjuvanted recombinant HIV-1 CN54gp140 effectively primes mucosal boost inoculations",
    abstract = "Background: Microneedles have previously been shown to enhance transdermal delivery of drugs and macromolecules. Their ability to effectively penetrate the dermis over a relatively large surface area offers potential use as minimally-invasive and painless replacements for more conventional parenteral vaccine regimens. In this study we compared the immune responses to HIV CN54gp140 using microneedles alone or a microneedle prime followed by mucosal boosting with monophosphoryl lipid A adjuvanted protein.Methods: Polymeric microneedle arrays that dissolve after piercing the skin were fabricated from poly(methylvinylether/ maleic acid) (Gantrez AN139) using laser-engineered siliconemicromould templates. Three groups of 8 BALB/c mice were primed using microneedles containing CN54gp140 and monophosphoryl lipid A. Three boosts were performed at two week intervals, using either the same microneedle formulation or vaginal or nasal administration of an antigen/adjuvant solution. Another group received four subcutaneous immunisations. Mice were sampled (serum and vaginal wash) prior to each vaccinationand two weeks post final immunization. Antigen-specific IgG and IgA production was assessed in the sera and mucosal lavage samples by quantitative ELISA. Splenocytes were harvested at necropsy and analysed for lymphocyte proliferation.Results: CN54gp140-specific serum IgG and lymphocyte proliferation responses were elicited in the subcutaneous immunization group and in those animals that were primed using microneedle delivery and boosted mucosally via the nasal route. Only the microneedle prime / intranasal boost group mounted a robust IgA response. In this group, IgG1 and IgG2a subtype quantification revealed a strong bias toward IgG2a.Conclusion: We have demonstrated that using a novel microneedle device to prime immunity followed by an intranasal boost elicits significant antigen-specific immune responses. This regimen generated similar serum IgG levels to the subcutaneous inoculations, but in contrast IgA was significantly elevated. This vaccination modality also induced a strong bias toward the IgG2a subtype suggesting a Th1 skewing of the immune response phenotype.",
    author = "Aditya Pattani and McKay, {Paul F} and Donnelly, {Ryan F} and Garland, {Martin J} and K Migalska and CM Cassidy and Malcolm, {R Karl} and Shattock, {Robin J} and Curran, {Rhonda M}",
    year = "2011",
    doi = "10.1089/aid.2011.1502",
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    Pattani, A, McKay, PF, Donnelly, RF, Garland, MJ, Migalska, K, Cassidy, CM, Malcolm, RK, Shattock, RJ & Curran, RM 2011, 'Microneedle mediated intradermal delivery of adjuvanted recombinant HIV-1 CN54gp140 effectively primes mucosal boost inoculations', AIDS Research and Human Retroviruses, vol. 27, no. 10. https://doi.org/10.1089/aid.2011.1502

    Microneedle mediated intradermal delivery of adjuvanted recombinant HIV-1 CN54gp140 effectively primes mucosal boost inoculations. / Pattani, Aditya; McKay, Paul F; Donnelly, Ryan F; Garland, Martin J; Migalska, K; Cassidy, CM; Malcolm, R Karl; Shattock, Robin J; Curran, Rhonda M.

    In: AIDS Research and Human Retroviruses, Vol. 27, No. 10, 2011.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Microneedle mediated intradermal delivery of adjuvanted recombinant HIV-1 CN54gp140 effectively primes mucosal boost inoculations

    AU - Pattani, Aditya

    AU - McKay, Paul F

    AU - Donnelly, Ryan F

    AU - Garland, Martin J

    AU - Migalska, K

    AU - Cassidy, CM

    AU - Malcolm, R Karl

    AU - Shattock, Robin J

    AU - Curran, Rhonda M

    PY - 2011

    Y1 - 2011

    N2 - Background: Microneedles have previously been shown to enhance transdermal delivery of drugs and macromolecules. Their ability to effectively penetrate the dermis over a relatively large surface area offers potential use as minimally-invasive and painless replacements for more conventional parenteral vaccine regimens. In this study we compared the immune responses to HIV CN54gp140 using microneedles alone or a microneedle prime followed by mucosal boosting with monophosphoryl lipid A adjuvanted protein.Methods: Polymeric microneedle arrays that dissolve after piercing the skin were fabricated from poly(methylvinylether/ maleic acid) (Gantrez AN139) using laser-engineered siliconemicromould templates. Three groups of 8 BALB/c mice were primed using microneedles containing CN54gp140 and monophosphoryl lipid A. Three boosts were performed at two week intervals, using either the same microneedle formulation or vaginal or nasal administration of an antigen/adjuvant solution. Another group received four subcutaneous immunisations. Mice were sampled (serum and vaginal wash) prior to each vaccinationand two weeks post final immunization. Antigen-specific IgG and IgA production was assessed in the sera and mucosal lavage samples by quantitative ELISA. Splenocytes were harvested at necropsy and analysed for lymphocyte proliferation.Results: CN54gp140-specific serum IgG and lymphocyte proliferation responses were elicited in the subcutaneous immunization group and in those animals that were primed using microneedle delivery and boosted mucosally via the nasal route. Only the microneedle prime / intranasal boost group mounted a robust IgA response. In this group, IgG1 and IgG2a subtype quantification revealed a strong bias toward IgG2a.Conclusion: We have demonstrated that using a novel microneedle device to prime immunity followed by an intranasal boost elicits significant antigen-specific immune responses. This regimen generated similar serum IgG levels to the subcutaneous inoculations, but in contrast IgA was significantly elevated. This vaccination modality also induced a strong bias toward the IgG2a subtype suggesting a Th1 skewing of the immune response phenotype.

    AB - Background: Microneedles have previously been shown to enhance transdermal delivery of drugs and macromolecules. Their ability to effectively penetrate the dermis over a relatively large surface area offers potential use as minimally-invasive and painless replacements for more conventional parenteral vaccine regimens. In this study we compared the immune responses to HIV CN54gp140 using microneedles alone or a microneedle prime followed by mucosal boosting with monophosphoryl lipid A adjuvanted protein.Methods: Polymeric microneedle arrays that dissolve after piercing the skin were fabricated from poly(methylvinylether/ maleic acid) (Gantrez AN139) using laser-engineered siliconemicromould templates. Three groups of 8 BALB/c mice were primed using microneedles containing CN54gp140 and monophosphoryl lipid A. Three boosts were performed at two week intervals, using either the same microneedle formulation or vaginal or nasal administration of an antigen/adjuvant solution. Another group received four subcutaneous immunisations. Mice were sampled (serum and vaginal wash) prior to each vaccinationand two weeks post final immunization. Antigen-specific IgG and IgA production was assessed in the sera and mucosal lavage samples by quantitative ELISA. Splenocytes were harvested at necropsy and analysed for lymphocyte proliferation.Results: CN54gp140-specific serum IgG and lymphocyte proliferation responses were elicited in the subcutaneous immunization group and in those animals that were primed using microneedle delivery and boosted mucosally via the nasal route. Only the microneedle prime / intranasal boost group mounted a robust IgA response. In this group, IgG1 and IgG2a subtype quantification revealed a strong bias toward IgG2a.Conclusion: We have demonstrated that using a novel microneedle device to prime immunity followed by an intranasal boost elicits significant antigen-specific immune responses. This regimen generated similar serum IgG levels to the subcutaneous inoculations, but in contrast IgA was significantly elevated. This vaccination modality also induced a strong bias toward the IgG2a subtype suggesting a Th1 skewing of the immune response phenotype.

    U2 - 10.1089/aid.2011.1502

    DO - 10.1089/aid.2011.1502

    M3 - Article

    VL - 27

    JO - AIDS Research and Human Retroviruses

    T2 - AIDS Research and Human Retroviruses

    JF - AIDS Research and Human Retroviruses

    SN - 0889-2229

    IS - 10

    ER -