Vaccine adjuvant systems: Enhancing the efficacy of sub-unit protein antigens

Perrie, Yvonne; Mohammed, Afzal-Ur-Rahman; Kirby, Daniel; McNeil, Sarah E.; Bramwell, Vincent W.

doi:10.1016/j.ijpharm.2008.04.036

Cited by 302 publications

(205 citation statements)

References 73 publications

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“…Nowadays, most of the vaccines under investigation are based on recombinant proteins or subunits of pathogens, because of improved safety and lower production cost compared to live or attenuated vaccines [32]. However, generally such vaccines are poorly immunogenic and fail to elicit robust cell-mediated immunity against intracellular pathogens.…”

Section: Discussionmentioning

confidence: 99%

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Hollow microneedle-mediated intradermal delivery of model vaccine antigen-loaded PLGA nanoparticles elicits protective T cell-mediated immunity to an intracellular bacterium

Groot

Mönkäre

et al. 2017

Journal of Controlled Release

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A B S T R A C TThe skin is an attractive organ for immunization due to the presence of a large number of epidermal and dermal antigen-presenting cells. Hollow microneedles allow for precise and non-invasive intradermal delivery of vaccines. In this study, ovalbumin (OVA)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles with and without TLR3 agonist poly(I:C) were prepared and administered intradermally by hollow microneedles. The capacity of the PLGA nanoparticles to induce a cytotoxic T cell response, contributing to protection against intracellular pathogens, was examined. We show that a single injection of OVA-loaded PLGA nanoparticles, compared to soluble OVA, primed both adoptively transferred antigen-specific naïve transgenic CD8 + and CD4 + T cells with markedly high efficiency. Applying a triple immunization protocol, PLGA nanoparticles primed also endogenous OVA-specific CD8 + T cells. Immune response, following immunization with in particular anionic PLGA nanoparticles co-encapsulated with OVA and poly(I:C), provided protection against a recombinant strain of the intracellular bacterium Listeria monocytogenes, secreting OVA. Taken together, we show that PLGA nanoparticle formulation is an excellent delivery system for protein antigen into the skin and that protective cellular immune responses can be induced using hollow microneedles for intradermal immunizations.

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Section: Discussionmentioning

confidence: 99%

“…Journal of Controlled Release 266 (2017) [27][28][29][30][31][32][33][34][35] 3.5. Protective immune response towards recombinant rLM-OVA after intradermal immunization using hollow microneedles CD8 + T cells play an essential role in clearance of the intracellular bacterium Listeria monocytogenes [31].…”

Section: Am De Groot Et Almentioning

confidence: 99%

Hollow microneedle-mediated intradermal delivery of model vaccine antigen-loaded PLGA nanoparticles elicits protective T cell-mediated immunity to an intracellular bacterium

Groot

Mönkäre

et al. 2017

Journal of Controlled Release

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“…Considerable efforts have been made to develop fish vaccines for decades. In order to elicit strong antibody response and long-term protection, fish vaccines are often coadministered with an adjuvant [2]. So far the types of adjuvants allowed in commercial fish vaccines are limited, however it is documented that these adjuvants, especially oil-based adjuvant (such as Freund's adjuvant), have deleterious side effects [3e5].…”

Section: Introductionmentioning

confidence: 99%

Complement C5a acts as molecular adjuvant in fish by enhancing antibody response to soluble antigen

LaPatra

et al. 2014

Fish & Shellfish Immunology

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“…[10,11] Conversely, small and soluble antigens, such as proteins and peptides, are poorly internalized and thus weakly immunogenic; therefore, an adjuvant is needed to intensify the immune response. [12,13] Triggering an efficient immune response to low-molecular-weight compounds 60 (haptens) is an even more challenging task because they are smaller and lack a peptide structure, so they cannot be presented by MHC II molecules unless they are conjugated to proteins prior to immunization. [14,15] One of the emerging strategies for increasing the efficiency of the phagocytosis step, thereby enhancing the antibody response, is the use of nanomaterials that can increase the size of the antigen 65 and modify its surface properties.…”

Section: Introductionmentioning

confidence: 99%

Carbon nanotube-protein carriers enhance size-dependent self-adjuvant antibody response to haptens

Parra

Abad‐Somovilla

Mercader

et al. 2013

Journal of Controlled Release

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Carbon nanotubes (CNTs) are nanomaterials with interesting emerging applications. Their 25 properties makes CNTs excellent candidates for use as new nanovehicles in drug delivery, immunization and diagnostics. In the current study, we assessed the immune-response-amplifying properties of CNTs to haptens by using azoxystrobin, the first developed strobilurin fungicide, as a model analyte. An azoxystrobin derivative bearing a carboxylated spacer arm (hapten AZc6) was covalently coupled to bovine serum albumin (BSA), and the resulting BSA-AZc6 conjugate was 30 covalently linked to four functionalized CNTs of different shapes and sizes, varying in diameter and length. These four types of CNT-based constructs were obtained using efficient, fast, and easy functionalization procedures based on microwave-assisted chemistry. New Zealand rabbits and BALB/c mice were immunized with BSA-AZc6 alone and with the four CNT-BSA-AZc6 constructs, both with and without Freund's adjuvant. The IgG-type antibody responses were assessed 35 in terms of the titer and affinity, paying special attention to the relationship between the immune response and the size and shape of the employed CNTs. Immunization with CNT-BSA-AZc6 resulted in enhanced titers and excellent affinities for azoxystrobin. More important, remarkable IgG responses were obtained even in the absence of an adjuvant, thus proving the self-adjuvanting capability of CNTs. Immunogens were able to produce strong anti-azoxystrobin immune responses 40 in rabbits even when administered at a BSA-AZc6 conjugate dose as low as 0.05 g. The short and thick CNT-BSA-AZc6 construct produced the best antibody response under all tested conditions.

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Vaccine adjuvant systems: Enhancing the efficacy of sub-unit protein antigens

Cited by 302 publications

References 73 publications

Hollow microneedle-mediated intradermal delivery of model vaccine antigen-loaded PLGA nanoparticles elicits protective T cell-mediated immunity to an intracellular bacterium

Hollow microneedle-mediated intradermal delivery of model vaccine antigen-loaded PLGA nanoparticles elicits protective T cell-mediated immunity to an intracellular bacterium

Complement C5a acts as molecular adjuvant in fish by enhancing antibody response to soluble antigen

Carbon nanotube-protein carriers enhance size-dependent self-adjuvant antibody response to haptens

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