Improved immune responses to influenza vaccination in the elderly using an immunostimulant patch

Frech, Sarah A.; Kenney, Richard T.; Spyr, Christian; Lazar, Hedvika; Viret, Jean-François; Herzog, Christian; Glück, Reinhard; Glenn, Gregory M.

doi:10.1016/j.vaccine.2004.06.036

Cited by 86 publications

(36 citation statements)

References 19 publications

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“…In this pilot study, a commercially available anti-influenza vaccine, which does not contain any adjuvant, was applied once on healthy human volunteers on skin areas as small as 16 or 32 cm 2 , respectively. In contrast to previous studies by other groups, we did not perform boost applications and no chemical or membrane permeabilization molecules were used as proposed by others (9,10). During the preparation of this manuscript, Yagi et al (32) demonstrated that five percutanous immunizations using CTL epitopes allow induction of CTL responses specific for melanoma and HIV peptides.…”

Section: Discussionmentioning

confidence: 94%

“…Only few concepts have been translated into clinical applications, i.e., pilot studies and Phase I clinical trials. As described in the introduction section, Glenn and his group (9,10) were the first group to immunize human volunteers via TC vaccination using patch systems. Those studies, however, focused on the induction of humoral immune responses.…”

Section: Discussionmentioning

confidence: 99%

“…Successful noninvasive vaccination by topical application of protein, peptides, and DNA has been shown in many mouse models where intradermal or transcutaneous (TC) vaccination induced both protective humoral and cellular immune responses (7,8). In a first attempt to immunize humans via TC vaccination, Glenn et al (9) induced robust immune responses against heat-labile enterotoxin from Escherichia coli in human volunteers using a patch system and demonstrated that improved Ab responses can be obtained in elderly individuals vaccinated against influenza by intradermal injection and additional application of an immunostimulatory patch containing heat-labile enterotoxin from E. coli (10). These studies, however, focused on the induction of humoral responses.…”

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confidence: 99%

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Transcutaneous Anti-Influenza Vaccination Promotes Both CD4 and CD8 T Cell Immune Responses in Humans

Vogt

Mahé²,

Costagliola

et al. 2008

The Journal of Immunology

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Induction of T cell responses has become one of the major goals in therapeutic vaccination against viral diseases and cancer. The use of the skin as target organ for vaccine has been spurred by recent implication of epithelial dendritic cells in CD8 cell cross-priming and suggests that vaccination via the transcutaneous (TC) route may be relevant in the induction of cellular immune responses. We have previously shown that TC application of nanoparticles, on human skin explants, allows targeting of epidermal dendritic cells, possibly via hair follicles. In this study, we have investigated cellular immune responses against an influenza protein-based vaccine by TC vaccination, compared with i.m. vaccination in humans. In this study on 11 healthy volunteers, we found that a newly developed protocol based on cyanocrylate skin surface stripping induced a significant increase in IFNγ-producing T cells specific for influenza vaccine by ELISPOT assays. Interestingly, TC vaccination induced both effector CD4 and CD8 T cell responses, whereas i.m. injection induced strong effector CD4 in the absence of CD8 T cells, as assessed by intracellular cytokine staining and tetramer analyses. This study proposes new perspectives for the development of vaccination strategies that trigger T cell immune responses in humans.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Transcutaneous Anti-Influenza Vaccination Promotes Both CD4 and CD8 T Cell Immune Responses in Humans

Vogt

Mahé²,

Costagliola

et al. 2008

The Journal of Immunology

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“…Based primarily on in vitro studies, it is envisaged that LCs undergo a process of maturation coordinate with migration, where they upregulate MHC, costimulatory, and adhesion molecules, and act as potent stimulators of naive CD4 and CD8 T cells when they arrive in the lymph node (3)(4)(5). Indeed, epicutaneous immunization strategies, which are presumed to involve LC, are effective at inducing functional CTL (6,7) and have led to clinical trials with positive preliminary findings for influenza and travelers' diarrhea (www.iomai.com) (8,9).…”

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confidence: 99%

Langerin Expressing Cells Promote Skin Immune Responses under Defined Conditions

Wang

Bursch

Kissenpfennig

et al. 2008

The Journal of Immunology

106

102

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There are conflicting data in the literature regarding the role of epidermal Langerhans cells (LC) in promoting skin immune responses. On one hand, LC can be extremely potent APCs in vitro, and are thought to be involved in contact hypersensitivity (CHS). On the other hand, it seems counterintuitive that a cell type continually exposed to pathogens at the organism’s barrier surfaces should readily trigger potent T cell responses. Indeed, LC depletion in one model led to enhanced contact hypersensitivity, suggesting they play a negative regulatory role. However, apparently similar LC depletion models did not show enhanced CHS, and in one case showed reduced CHS. In this study we found that acute depletion of mouse LC reduced CHS, but the timing of toxin administration was critical: toxin administration 3 days before priming did not impair CHS, whereas toxin administration 1 day before priming did. We also show that LC elimination reduced the T cell response to epicutaneous immunization with OVA protein Ag. However, this reduction was only observed when OVA was applied on the flank skin, and not on the ear. Additionally, peptide immunization was not blocked by depletion, regardless of the site. Finally we show that conditions which eliminate epidermal LC but spare other Langerin+ DC do not impair the epicutaneous immunization response to OVA. Overall, our results reconcile previous conflicting data in the literature, and suggest that Langerin+ cells do promote T cell responses to skin Ags, but only under defined conditions.

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“…9 Physical co-delivery of antigen and adjuvant appears to be more important with the use of certain routes, such as SC, since one study in mice showed that topical application of CpG induced more efficient cross-presentation and induction of T cell responses to an antigen injected IM or SC than if the CpG and antigen were admixed. 10 Furthermore, heat-labile enterotoxin applied by transdermal patch has been shown in both animals 11 and humans 12 to improve immune responses against antigen injected IM deep to the patch. It is thought that these topical adjuvants activate Langerhans cells in the skin, which migrate to the same draining lymph nodes as the injected antigen.…”

Section: Specific Factors To Consider For Translating Pre-clinical Rementioning

confidence: 99%

Novel vaccines and adjuvant systems: The utility of animal models for predicting immunogenicity in humans

Davis¹

2008

Human Vaccines

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as for the prevention or treatment of cancer, allergy and autoimmune disorders, lifestyle related conditions (e.g., hypertension, smoking, contraception) and miscellaneous pathological states (e.g., Alzheimer's dementia). All vaccines contain one or more antigens, that can take various forms from peptides up to whole cells, and today many vaccines also contain an adjuvant. Such adjuvants are designed to affect the biodistribution of the antigen (e.g., provide a depot effect or target the antigen to particular immune cells) and/ or enhance resulting immune responses through direct activation of specific immune cells.Antigen discovery is not a new science, and for a long time there have been plenty of novel antigen candidates that were not being developed for want of an adjuvant system more potent than alum, which was, until fairly recently, the only adjuvant in a licensed vaccine. Alum is a relatively weak adjuvant with a strong Th2 bias, hence effective mostly for induction of antibodies. Thus, the need for novel adjuvants was particularly urgent for vaccines being designed for therapeutic applications where cell-mediated immunity is required for efficacy.Development of new vaccine adjuvants has been facilitated by two interrelated factors: (1) the rapidly expanding knowledge of the immune system, in particular the mechanisms by which the immune system naturally recognizes and responds to pathogens and how this innate immune activation is translated into adaptive immunity with memory, and (2) the discovery of natural or synthetic agonists for receptors that detect pathogen-associated molecular patterns and their development as potent new generation vaccine adjuvants.Successful development of a new vaccine formulation requires that the antigen and adjuvant components in the formulation are compatible, chemically distinct and detectable for quality control purposes. As well, they need to be sufficiently stable, have scalable and cost-effective synthesis, and last but certainly not least, be effective in inducing an adequate and appropriate immune response. The risk for most of these elements can be ascertained fairly quickly, but efficacy is a huge challenge. Certainly no one would consider testing a novel vaccine in humans without having achieved encouraging immunogenicity data in animals, but how useful or meaningful is the animal data for designing human studies and predicting outcome? There is a fair degree of judgment and guesswork required, and failure to do this well can lead to protracted and costly drug development pathways. Even with ultimate testing in human clinical trials, it may not be possible to measure efficacy directly when the pathogen is rarely Animal models are essential for acquiring safety, immunogenicity and efficacy data to support the development of novel vaccines. However, extrapolating such results to designing human trials is challenging due to species-specific differences in responses to antigens, adjuvants and pathogens. As well, most early vaccine work is conducted with in-bred mous...

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Improved immune responses to influenza vaccination in the elderly using an immunostimulant patch

Cited by 86 publications

References 19 publications

Transcutaneous Anti-Influenza Vaccination Promotes Both CD4 and CD8 T Cell Immune Responses in Humans

Transcutaneous Anti-Influenza Vaccination Promotes Both CD4 and CD8 T Cell Immune Responses in Humans

Langerin Expressing Cells Promote Skin Immune Responses under Defined Conditions

Novel vaccines and adjuvant systems: The utility of animal models for predicting immunogenicity in humans

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