Aluminium hydroxide potentiates a protective Th1 biased immune response against polio virus that allows for dose sparing in mice and rats

Andreasen, Lars Vibe; Hansen, Lasse Bøllehuus; Andersen, Peter; Agger, Else Marie; Dietrich, Jes

doi:10.1016/j.vaccine.2015.02.011

Cited by 19 publications

(10 citation statements)

References 45 publications

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“…As a result, WHO has investigated cost-saving measures to reduce antigen dose. One way to achieve this is with the use of adjuvants, such as dmLT 21 or aluminium hydroxide 22 . Alternatively, approaches such as intradermal injection, microinjectors and microneedle patch technologies, are being explored to target the IPV vaccine to the skin which has been shown to be abundant in antigen presenting cells 7 .…”

Section: Discussionmentioning

confidence: 99%

Inactivated poliovirus type 2 vaccine delivered to rat skin via high density microprojection array elicits potent neutralising antibody responses

Muller

Pearson

Fernando

et al. 2016

Sci Rep

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Polio eradication is progressing rapidly, and the live attenuated Sabin strains in the oral poliovirus vaccine (OPV) are being removed sequentially, starting with type 2 in April 2016. For risk mitigation, countries are introducing inactivated poliovirus vaccine (IPV) into routine vaccination programs. After April 2016, monovalent type 2 OPV will be available for type 2 outbreak control. Because the current IPV is not suitable for house-to-house vaccination campaigns (the intramuscular injections require health professionals), we developed a high-density microprojection array, the Nanopatch, delivered monovalent type 2 IPV (IPV2) vaccine to the skin. To assess the immunogenicity of the Nanopatch, we performed a dose-matched study in rats, comparing the immunogenicity of IPV2 delivered by intramuscular injection or Nanopatch immunisation. A single dose of 0.2 D-antigen units of IPV2 elicited protective levels of poliovirus antibodies in 100% of animals. However, animals receiving IPV2 by IM required at least 3 immunisations to reach the same neutralising antibody titres. This level of dose reduction (1/40th of a full dose) is unprecedented for poliovirus vaccine delivery. The ease of administration coupled with the dose reduction observed in this study points to the Nanopatch as a potential tool for facilitating inexpensive IPV for mass vaccination campaigns.

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Section: Discussionmentioning

confidence: 99%

Inactivated poliovirus type 2 vaccine delivered to rat skin via high density microprojection array elicits potent neutralising antibody responses

Muller

Pearson

Fernando

et al. 2016

Sci Rep

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“…As a result of these factors, there are several investigations are underway to make IPV more accessible, by reducing the cost of vaccination, through stretching the already constrained supply of IPV through dose-sparing and by increasing ease of administration 10 , 11 . These dose sparing approaches include: use of adjuvants 12 , ID injectors 13 – 16 , jet injectors 17 – 22 and finally microarray patch (MAP) technologies 10 , 11 . The use of ID injection using standard ID needle and syringes is also being clinically investigated 13 for poliovirus vaccination.…”

Section: Introductionmentioning

confidence: 99%

High-density microprojection array delivery to rat skin of low doses of trivalent inactivated poliovirus vaccine elicits potent neutralising antibody responses

Muller

Fernando

Owens

et al. 2017

Sci Rep

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To secure a polio-free world, the live attenuated oral poliovirus vaccine (OPV) will eventually need to be replaced with inactivated poliovirus vaccines (IPV). However, current IPV delivery is less suitable for campaign use than OPV, and more expensive. We are progressing a microarray patch delivery platform, the Nanopatch, as an easy-to-use device to administer vaccines, including IPV. The Nanopatch contains an ultra-high density array (10,000/cm2) of short (~230 μm) microprojections that delivers dry coated vaccine into the skin. Here, we compare the relative immunogenicity of Nanopatch immunisation versus intramuscular injection in rats, using monovalent and trivalent formulations of IPV. Nanopatch delivery elicits faster antibody response kinetics, with high titres of neutralising antibody after just one (IPV2) or two (IPV1 and IPV3) immunisations, while IM injection requires two (IPV2) or three (IPV1 and IPV3) immunisations to induce similar responses. Seroconversion to each poliovirus type was seen in 100% of rats that received ~1/40th of a human dose of IPV delivered by Nanopatch, but not in rats given ~1/8th or ~1/40th dose by IM injection. Ease of administration coupled with dose reduction observed in this study suggests the Nanopatch could facilitate inexpensive IPV vaccination in campaign settings.

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“…Moreover, adsorption to aluminum of TLR ligands co-localizes antigen and adjuvant, and facilitates reduction of antigen and/or TLR ligand dose [5], [6], [7]. Therefore it is of high interest to develop aluminum salt-based formulations of other pattern recognition receptor (PRR) ligands (besides TLR4 agonists) to enhance antigen-specific Th1-type immunogenicity and protective efficacy [5], [8], [9].…”

Section: Introductionmentioning

confidence: 99%

Adsorption of a synthetic TLR7/8 ligand to aluminum oxyhydroxide for enhanced vaccine adjuvant activity: A formulation approach

Fox

Orr

Hoeven

et al. 2016

Journal of Controlled Release

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For nearly a century, aluminum salts have been the most widely used vaccine adjuvant formulation, and have thus established a history of safety and efficacy. Nevertheless, for extremely challenging disease targets such as tuberculosis or HIV, the adjuvant activity of aluminum salts may not be potent enough to achieve protective efficacy. Adsorption of TLR ligands to aluminum salts facilitates enhanced adjuvant activity, such as in the human papilloma virus vaccine Cervarix®. However, some TLR ligands such as TLR7/8 agonist imidazoquinolines do not efficiently adsorb to aluminum salts. The present report describes a formulation approach to solving this challenge by developing a lipid-based nanosuspension of a synthetic TLR7/8 ligand (3M-052) that facilitates adsorption to aluminum oxyhydroxide via the structural properties of the helper lipid employed. In immunized mice, the aluminum oxyhydroxide-adsorbed formulation of 3M-052 enhanced antibody and TH1-type cellular immune responses to vaccine antigens for tuberculosis and HIV.

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Aluminium hydroxide potentiates a protective Th1 biased immune response against polio virus that allows for dose sparing in mice and rats

Abstract: The IPV-aluminium hydroxide formulation constitutes a promising vaccine capable of generating strong Th1 immunity against infection with all three serotypes. A phase I/II clinical study was recently initiated.

Cited by 19 publications

References 45 publications

Inactivated poliovirus type 2 vaccine delivered to rat skin via high density microprojection array elicits potent neutralising antibody responses

Inactivated poliovirus type 2 vaccine delivered to rat skin via high density microprojection array elicits potent neutralising antibody responses

High-density microprojection array delivery to rat skin of low doses of trivalent inactivated poliovirus vaccine elicits potent neutralising antibody responses

Adsorption of a synthetic TLR7/8 ligand to aluminum oxyhydroxide for enhanced vaccine adjuvant activity: A formulation approach

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