Peter Andersen

Statens Serum Institut, København, Capital Region, Denmark

Are you Peter Andersen?

Claim your profile

Publications (182)802.57 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The application of cationic liposomes as vaccine delivery systems and adjuvants has been investigated extensively over the last few decades. However, cationic liposomes are, in general, not sufficiently immunostimulatory, which is why the combination of liposomes with immunostimulating ligands has arisen as a strategy in the development of novel adjuvant systems. Within the last 5 years, two novel adjuvant systems based on cationic liposomes incorporating Toll-like receptor or non-Toll-like receptor immunostimulating ligands have progressed from preclinical testing in smaller animal species to clinical testing in humans. The immune responses that these clinical candidates induce are primarily of the Th1 type for which there is a profound unmet need. Furthermore, a number of new cationic liposome-forming surfactants with notable immunostimulatory properties have been discovered. In this article we review the recent progress on the application of cationic liposomes as vaccine delivery systems/adjuvants.
    Expert Review of Vaccines 04/2011; 10(4):513-21. · 4.22 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: INTRODUCTION: Liposomes remain at the forefront of drug and vaccine design owing to their well-documented abilities to act as delivery vehicles. Nevertheless, the concept of liposomes as delivery vehicles is not a new one, with most works focusing on their use for the delivery of genes and drugs. However, in the last 10 years a significant amount of research has focused on using liposomes as vaccine adjuvants, not only as an antigen delivery vehicle but also as a tool to increase the immunogenicity of peptide and protein antigens. AREAS COVERED: This paper reviews liposomal adjuvants now in vaccine development, with particular emphasis on their adjuvant mechanism and how specific physicochemical characteristics of liposomes affect the immune response. The inclusion of immunomodulators is also discussed, with prominence given to Toll-like receptor ligands. EXPERT OPINION: The use of liposomes as vaccine delivery systems is evolving rapidly owing to the combined increase in technological advances and understanding of the immune system. Liposomes that contain and deliver immunostimulators and antigens are now being developed to target diseases that require stimulation of both humoral and cell-mediated immune responses. The CAF liposomal system, described in detail in this review, is one liposomal model that shows such flexibility.
    Expert Opinion on Drug Delivery 03/2011; 8(4):505-19. · 4.87 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The immunostimulatory capacities of cationic liposomes are well-documented and are attributed both to inherent immunogenicity of the cationic lipid and more physical capacities such as the formation of antigen depots and antigen delivery. Very few studies have however been conducted comparing the immunostimulatory capacities of different cationic lipids. In the present study we therefore chose to investigate three of the most well-known cationic liposome-forming lipids as potential adjuvants for protein subunit vaccines. The ability of 3β-[N-(N',N'-dimethylaminoethane)carbomyl] cholesterol (DC-Chol), 1,2-dioleoyl-3-trimethylammonium propane (DOTAP), and dimethyldioctadecylammonium (DDA) liposomes incorporating immunomodulating trehalose dibehenate (TDB) to form an antigen depot at the site of injection (SOI) and to induce immunological recall responses against coadministered tuberculosis vaccine antigen Ag85B-ESAT-6 are reported. Furthermore, physical characterization of the liposomes is presented. Our results suggest that liposome composition plays an important role in vaccine retention at the SOI and the ability to enable the immune system to induce a vaccine specific recall response. While all three cationic liposomes facilitated increased antigen presentation by antigen presenting cells, the monocyte infiltration to the SOI and the production of IFN-γ upon antigen recall was markedly higher for DDA and DC-Chol based liposomes which exhibited a longer retention profile at the SOI. A long-term retention and slow release of liposome and vaccine antigen from the injection site hence appears to favor a stronger Th1 immune response.
    Molecular Pharmaceutics 02/2011; 8(1):153-61. · 4.57 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: All tuberculosis vaccines currently in clinical trials are designed as prophylactic vaccines based on early expressed antigens. We have developed a multistage vaccination strategy in which the early antigens Ag85B and 6-kDa early secretory antigenic target (ESAT-6) are combined with the latency-associated protein Rv2660c (H56 vaccine). In CB6F1 mice we show that Rv2660c is stably expressed in late stages of infection despite an overall reduced transcription. The H56 vaccine promotes a T cell response against all protein components that is characterized by a high proportion of polyfunctional CD4(+) T cells. In three different pre-exposure mouse models, H56 confers protective immunity characterized by a more efficient containment of late-stage infection than the Ag85B-ESAT6 vaccine (H1) and BCG. In two mouse models of latent tuberculosis, we show that H56 vaccination after exposure is able to control reactivation and significantly lower the bacterial load compared to adjuvant control mice.
    Nature medicine 02/2011; 17(2):189-94. · 27.14 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: It has been clearly demonstrated that in vitro, virulent M. tuberculosis can favor necrosis over apoptosis in infected macrophages, and this has been suggested as a mechanism for evading the host immune response. We recently reported that an effect consistent with this hypothesis could be observed in cells from the blood of TB patients, and in this paper, we review what is known about evasion strategies employed by M. tuberculosis and in particular consider the possible interaction of the apoptosis-inhibiting effects of M. tuberculosis infection with another factor (IL-4) whose expression is thought to play a role in the failure to control M. tuberculosis infection. It has been noted that IL-4 may exacerbate TNF-α-induced pathology, though the mechanism remains unexplained. Since pathology in TB typically involves inflammatory aggregates around infected cells, where TNF-α plays an important role, we predicted that IL-4 would inhibit the ability of cells to remove M. tuberculosis by apoptosis of infected cells, through the extrinsic pathway, which is activated by TNF-α. Infection of human monocytic cells with mycobacteria in vitro, in the presence of IL-4, appears to promote necrosis over apoptosis in infected cells-a finding consistent with its suggested role as a factor in pathology during M. tuberculosis infection.
    Clinical and Developmental Immunology 01/2011; 2011:678570. · 3.06 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Bovine tuberculosis (bTB) is diagnosed in naturally infected populations exposed to a wide variety of other pathogens. This study describes the cell-mediated immune responses of cattle exposed to Mycobacterium avium subspecies paratuberculosis (Map) and Mycobacterium avium subspecies avium with particular reference to routine antefmortem Mycobacterium bovis diagnostic tests. The IFN-γ released in response to stimulated blood was found to peak later in the Map-exposed group and was more sustained when compared to the Maa-exposed group. There was a very close correlation between the responses to the purified protein derivatives (PPD) used for stimulation (PPDa, PPDb, and PPDj) with PPDa and PPDj most closely correlated. On occasion, in the Map-infected cattle, PPDb-biased responses were seen compared to PPDa suggesting that some Map-infected cattle could be misclassified as M. bovis infected using this test with these reagents. This bias was not seen when PPDj was used. SICCT results were consistent with the respective infections and all calves would have been classed skin test negative.
    Veterinary medicine international. 01/2011; 2011:145092.
  • [Show abstract] [Hide abstract]
    ABSTRACT: New TB vaccines are urgently needed because of the apparent lack of effect of the BCG vaccine on rates of adult contagious pulmonary tuberculosis and the risk of disseminated BCG disease in immunocompromised individuals. Since BCG appears to protect children, the primary target for vaccine development is a booster vaccine for adults but such vaccines ideally need to be able to efficiently prime mycobacterially naïve individuals as well as boost individuals previously vaccinated with BCG and those latently infected with TB. Protective immunity against Mycobacterium tuberculosis depends mainly on the generation of a Th1-type cellular immune response characterized by interferon-gamma (IFN-γ) production. In the present study, we monitored safety and IFN-γ responses in healthy BCG-vaccinated and prior or latently TB-infected individuals receiving a novel vaccine composed of the fusion protein Ag85B-ESAT-6 combined with the adjuvant IC31(®), administered at 0 and 2 months. Vaccination caused few local or systemic adverse effects besides transient soreness at the injection site, but it elicited strong antigen-specific T cell responses against Ag85B-ESAT-6 and both the Ag85B and ESAT-6 components, that could be augmented by second vaccination. The strong responses persisted through 32 weeks of follow-up, indicating the induction of a persistent memory response in the vaccine recipients.
    Vaccine 01/2011; 29(11):2100-9. · 3.77 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Trivalent inactivated vaccines (TIV) against influenza are given to 350 million people every year. Most of these are non-adjuvanted vaccines whose immunogenicity and protective efficacy are considered suboptimal. Commercially available non-adjuvanted TIV are known to elicit mainly a humoral immune response, whereas the induction of cell-mediated immune responses is negligible. Recently, a cationic liposomal adjuvant (dimethyldioctadecylammonium/trehalose 6,6'-dibehenate, CAF01) was developed. CAF01 has proven to enhance both humoral and cell-mediated immune responses to a number of different experimental vaccine candidates. In this study, we compared the immune responses in ferrets to a commercially available TIV with the responses to the same vaccine mixed with the CAF01 adjuvant. Two recently circulating H1N1 viruses were used as challenge to test the vaccine efficacy. CAF01 improved the immunogenicity of the vaccine, with increased influenza-specific IgA and IgG levels. Additionally, CAF01 promoted cellular-mediated immunity as indicated by interferon-gamma expressing lymphocytes, measured by flow cytometry. CAF01 also enhanced the protection conferred by the vaccine by reducing the viral load measured in nasal washes by RT-PCR. Finally, CAF01 allowed for dose-reduction and led to higher levels of protection compared to TIV adjuvanted with a squalene emulsion. The data obtained in this human-relevant challenge model supports the potential of CAF01 in future influenza vaccines.
    PLoS ONE 01/2011; 6(8):e22891. · 3.73 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Tuberculosis (TB) remains a major killer worldwide. The only available TB-vaccine, the nearly century-old Mycobacterium bovis BCG, has had only a limited effect on TB incidence. Therefore, developing new TB vaccines is a key priority, and the first new generation TB vaccines are now being tested in clinical trials. Here we describe the development and first testing in humans of a novel, wholly synthetic TB subunit vaccine. This vaccine has proven safe and highly immunogenic in all species in which it was tested, including mice, guinea pigs, non-human primates and humans. Most encouragingly, following vaccination in humans, strong IFN-γ responses persisted through at least 2½ years of follow-up, indicating induction of a substantial memory response by this new TB vaccine. These findings encourage further preclinical and clinical studies with TB subunit vaccines and cellular immunity-stimulating new adjuvants.
    Human vaccines 12/2010; 6(12):1007-15. · 3.14 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The combination of nucleic acid-based Toll-like receptor (TLR)-3 or TLR9 agonists and cationic liposomes constitutes an effective vaccine adjuvant approach for eliciting CD8+ T-cell responses. However, complexing cationic liposomes and oppositely charged oligonucleotides generally results in highly unstable and heterogeneous formulations with limited clinical applicability. The aim of this study was to design, formulate, and carefully characterize a stable CD8-inducing adjuvant based on the TLR3 ligand polyinosinic-polycytidylic acid [poly(I:C)] incorporated into a cationic adjuvant system (CAF01) composed of dimethyldioctadecylammonium (DDA) and trehalose 6,6'-dibehenate (TDB). For this purpose, a modified double emulsion solvent evaporation method was investigated for complexation of high amounts of anionic poly(I:C) to gel-state DDA/TDB liposomes. Addition of a volatile, water-miscible co-solvent (ethanol) to the outer water phase enabled preparation of colloidally stable liposomes, presumably by reducing the poly(I:C)-enhanced rigidity of the lipid bilayer. Cryo-transmission electron microscopy (TEM) revealed the formation of unilamellar as well as multilamellar liposomes, the latter suggesting that poly(I:C) is intercalated between the membrane bilayers in an onion-like structure. Finally, immunization of mice with the model antigen ovalbumin (OVA) and DDA/TDB/poly(I:C) liposomes induced a remarkably strong, antigen-specific CD8+ T-cell response, which was maintained for more than two months. Importantly, whereas injection of soluble poly(I:C) led to rapid production of the pro-inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6 in serum, administration of poly(I:C) in complex with the cationic DDA/TDB liposomes prevented this non-specific systemic pro-inflammatory response. These data emphasize the importance of improving the quality of the vaccine formulation to indeed overcome some of the major obstacles for using CD8-inducing agents such as poly(I:C) in future subunit vaccines.
    Journal of Controlled Release 11/2010; 150(3):307-17. · 7.63 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The combination of delivery systems like cationic liposomes and immunopotentiators such as Toll-like receptor (TLR) ligands is a promising approach for rational vaccine adjuvant design. The purpose of this study was to investigate how the incorporation of the poorly soluble TLR4 agonist monophosphoryl lipid A (MPL) into cationic liposomes based on dimethyldioctadecylammonium (DDA) and trehalose 6,6'-dibehenate (TDB) influenced the physicochemical and immunological properties of the liposomes. The DDA/TDB/MPL liposomes were characterized with regard to particle size, poly dispersity, surface charge, stability and thermodynamic properties. The adjuvant formulations were tested in vivo in mice using ovalbumin (OVA) as model antigen. Integration of MPL into the bilayer structure of DDA/TDB liposomes was evident from a decreased phase transition temperature, an improved membrane packing, and a reduction in surface charge. The particle size and favorable liposome storage stability were not affected by MPL. In mice, DDA/TDB/MPL liposomes induced an antigen-specific CD8(+) T-cell response and a humoral response. Enhancing the solubility of MPL by inclusion into the bilayer of DDA/TDB liposomes changes the membrane characteristics of the adjuvant system and provides the liposomes with CD8(+) T-cell inducing properties without compromising humoral responses.
    Pharmaceutical Research 11/2010; 28(3):553-62. · 4.74 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: One third of the world's population is infected with Mycobacterium tuberculosis (M.tb). A vaccine that would prevent progression to TB disease will have a dramatic impact on the global TB burden. We propose that antigens of M.tb that are preferentially expressed during latent infection will be excellent candidates for post-exposure vaccination. We therefore assessed human T cell recognition of two such antigens, Rv2660 and Rv2659. Expression of these was shown to be associated with non-replicating persistence in vitro. After six days incubation of PBMC from persons with latent tuberculosis infection (LTBI) and tuberculosis (TB) disease, Rv2660 and Rv2659 induced IFN-γ production in a greater proportion of persons with LTBI, compared with TB diseased patients. Persons with LTBI also had increased numbers of viable T cells, and greater specific CD4(+) T cell proliferation and cytokine expression capacity. Persons with LTBI preferentially recognize Rv2659 and Rv2660, compared with patients with TB disease. These results suggest promise of these antigens for incorporation into post-exposure TB vaccines.
    Vaccine 10/2010; 29(1):51-7. · 3.77 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: With respect to liposomes as delivery vehicles and adjuvants for vaccine antigens, the role of vesicle surface charge remains disputed. In the present study we investigate the influence of liposome surface charge and antigen-liposome interaction on the antigen depot effect at the site of injection (SOI). The presence of liposome and antigen in tissue at the SOI as well as the draining lymphatic tissue was quantified to analyse the lymphatic draining of the vaccine components. Furthermore investigations detailing cytokine production and T-cell antigen specificity were undertaken to investigate the relationship between depot effect and the ability of the vaccine to induce an immune response. Our results suggest that cationic charge is an important factor for the retention of the liposomal component at the SOI, and a moderate to high (>50%) level of antigen adsorption to the cationic vesicle surface was required for efficient antigen retention in the same tissue. Furthermore, neutral liposomes expressing poor levels of antigen retention were limited in their ability to mediate long term (14 days) antigen presentation to circulating antigen specific T-cells and to induce the Th1 and Th17 arms of the immune system, as compared to antigen adsorbing cationic liposomes. The neutral liposomes did however induce the production of IL-5 at levels comparable to those induced by cationic liposomes, indicating that neutral liposomes can induce a weak Th2 response.
    Journal of Controlled Release 04/2010; 145(2):102-8. · 7.63 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The current tuberculosis (TB) vaccine, bacille Calmette-Guérin (BCG), does not provide adequate protection against TB disease in children. Furthermore, more efficacious TB vaccines are needed for children with immunodeficiencies such as HIV infection, who are at highest risk of disease. To characterize mycobacteria-specific T cells in children who might benefit from vaccination against TB, focusing on responses to antigens contained in novel TB vaccines. Methods: Whole blood was collected from three groups of BCG-vaccinated children: HIV-seronegative children receiving TB treatment (n = 30), HIV-infected children (n = 30), and HIV-unexposed healthy children (n = 30). Blood was stimulated with Ag85B and TB10.4, or purified protein derivative, and T-cell cytokine production by CD4 and CD8 was determined by flow cytometry. The memory phenotype of antigen-specific CD4 and CD8 T cells was also determined. Mycobacteria-specific CD4 and CD8 T-cell responses were detectable in all three groups of children. Children receiving TB treatment had significantly higher frequencies of antigen-specific CD4 T cells compared with HIV-infected children (P = 0.0176). No significant differences in magnitude, function, or phenotype of specific T cells were observed in HIV-infected children compared with healthy control subjects. CD4 T cells expressing IFN-gamma, IL-2, or both expressed a CD45RA(-)CCR7(-)CD27(+/-) effector memory phenotype. Mycobacteria-specific CD8 T cells expressed mostly IFN-gamma in all groups of children; these cells expressed CD45RA(-)CCR7(-)CD27(+/-) or CD45RA(+)CCR7(-)CD27(+/-) effector memory phenotypes. Mycobacteria-specific T-cell responses could be demonstrated in all groups of children, suggesting that the responses could be boosted by new TB vaccines currently in clinical trials.
    American Journal of Respiratory and Critical Care Medicine 03/2010; 182(1):120-9. · 11.04 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Though widely used, the BCG vaccine has had little apparent effect on rates of adult pulmonary tuberculosis. Moreover, the risk of disseminated BCG disease in immunocompromised individuals means that improved TB vaccines ideally need to be able to efficiently prime mycobacterially-naïve individuals as well as boost individuals previously vaccinated with BCG. Protective immunity against Mycobacterium tuberculosis is thought to depend on the generation of a Th1-type cellular immune response characterized by interferon-gamma (IFN-gamma) production. In the present study, we monitored safety and IFN-gamma responses in healthy TB-naïve humans receiving an entirely novel vaccine, composed of the fusion protein Ag85B-ESAT-6, administered at 0 and 2 months either as recombinant protein alone or combined with two concentrations of the novel adjuvant IC31. Vaccination did not cause local or systemic adverse effects besides transient soreness at the injection site, but it elicited strong antigen-specific T cell responses against H1 and both the Ag85B and the ESAT-6 components. These strong responses persisted through 2.5 years of follow-up, indicating the induction of a substantial memory response in the vaccine recipients.
    Vaccine 03/2010; 28(20):3571-81. · 3.77 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The mycobacterial cord factor trehalose-6,6-dimycolate (TDM) and its synthetic analog trehalose-6,6-dibehenate (TDB) are potent adjuvants for Th1/Th17 vaccination that activate Syk-Card9 signaling in APCs. In this study, we have further investigated the molecular mechanism of innate immune activation by TDM and TDB. The Syk-coupling adapter protein FcRgamma was essential for macrophage activation and Th17 adjuvanticity. The FcRgamma-associated C-type lectin receptor Mincle was expressed in macrophages and upregulated by TDM and TDB. Recombinant Mincle-Fc fusion protein specifically bound to the glycolipids. Genetic ablation of Mincle abolished TDM/TDB-induced macrophage activation and induction of T cell immune responses to a tuberculosis subunit vaccine. Macrophages lacking Mincle or FcRgamma were impaired in the inflammatory response to Mycobacterium bovis bacillus Calmette-Guérin. These results establish that Mincle is a key receptor for the mycobacterial cord factor and controls the Th1/Th17 adjuvanticity of TDM and TDB.
    The Journal of Immunology 02/2010; 184(6):2756-60. · 5.52 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Most novel vaccines against infectious diseases are based on recombinant Ag; however, only few studies have compared Ag-specific immune responses induced by natural infection with that induced by the same Ag in a recombinant form. Here, we studied the epitope recognition pattern of the tuberculosis vaccine Ag, TB10.4, in a recombinant form, or when expressed by the pathogen Mycobacterium tuberculosis (M.tb), or by the current anti-tuberculosis vaccine, Mycobacterium bovis BCG. We showed that BCG and M.tb induced a similar CD4+ T-cell specific TB10.4 epitope-pattern, which differed completely from that induced by recombinant TB10.4. This difference was not due to post-translational modifications of TB10.4 or because TB10.4 is secreted from BCG and M.tb as a complex with Rv0287. In addition, BCG and TB10.4/CAF01 were both taken up by DC and macrophages in vivo, and in vitro uptake experiments revealed that both TB10.4 and BCG were transported to Lamp+-compartments. BCG and TB10.4 however, were directed to different types of Lamp+-compartments in the same APC, which may lead to different epitope recognition patterns. In conclusion, we show that different vectors can induce completely different recognition of the same protein.
    European Journal of Immunology 02/2010; 40(5):1342-54. · 4.97 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Adjuvants constitute a critical component in vaccine development in terms of both stimulating and directing immune responses of a suitable profile to promote protection against a diverse range of disease targets. In the past, the field of adjuvant research was mainly dominated by empirical testing and serendipity. However, there is a strong need to develop new generations of adjuvants based on rational design, as well as a requirement to characterise and comprehend their mechanism(s) of action. Adjuvant development can be characterised as an iterative process where potential candidates are repeatedly tested in vitro and in vivo for immunogenicity and optimised in terms of formulation and delivery. Novel lead candidates of adjuvants with a suitable immunological profile relative to specific disease targets are subsequently selected and evaluated in efficacy studies. A central aspect in such a development and selection process is to determine the adjuvant activity on T-cell function in vivo. Expanding our knowledge on these mechanisms will improve our chance of developing new successful vaccines designed to target specific diseases.
    Methods in molecular biology (Clifton, N.J.) 01/2010; 626:213-29. · 1.29 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The chlamydial proteins CT443 (OmcB) and CT521 (rl16) have previously been identified as human B and/or T cell targets during a chlamydial infection in humans. Here we compare the protective effector mechanism promoted by a fusion protein composed of CT521 and CT443 (CTH1) with a primary intranasal Chlamydia muridarum infection known to provide high levels of protection against a genital chlamydial challenge. The fusion protein CTH1, adjuvanted with a strong Th1 inducing cationic adjuvant (CAF01), significantly reduced the bacterial shedding compared to a control group in both a C. trachomatis Serovar D and C. muridarum challenge model. The CTH1/CAF01 vaccine was found to induce polyfunctional T cells consisting of TNFalpha/IL-2 and TNFalpha/IL-2/IFN-gamma positive cells and high titers of CTH1 specific IgG2a and IgG1. By depletion experiments the protection in the C. muridarum challenge model was demonstrated to be mediated solely by CD4(+) T cells. In comparison, an intranasal infection with C. muridarum induced a T cell response that consisted predominantly of TNFalpha/IFN-gamma co-expressing effector CD4(+) T cells and an antibody response consisting of C. muridarum specific IgG1, IgG2a but also IgA. This response was associated with a high level of protection against challenge-a protection that was only partially dependent on CD4(+) T cells. Furthermore, whereas the antibody response induced by intranasal infection was strongly reactive against the native antigens displayed in the chlamydial elementary body, only low levels of antibodies against this preparation were found after CTH1/CAF01 immunization. Our data demonstrate that CTH1 vaccination promotes a CD4(+) T cell dependent protective response but compared with intranasal C. muridarum infection lacks a CD4 independent protective mechanism for complete protection.
    PLoS ONE 01/2010; 5(5):e10768. · 3.73 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Bioneedles are small hollow sugar based needles administered with a simple compressed air device. In the present study we investigate how incorporation of a subunit vaccine based on TB vaccine hybrid Ag85B-ESAT-6 adjuvated with CAF01 into Bioneedles affects its immunogenicity as well as its ability to protect against TB in a mouse model. The CMI response measured by IFN-γ and antigen specific CD4+ T-cells was, two weeks after the last vaccination, significantly lower in the group immunized with Bioneedle-incorporated vaccine compared to the conventional vaccine, using syringe and needle. However, at four, nine and 52 weeks after vaccination we observed similar high IFN-γ levels in the Bioneedle group and the group vaccinated using syringe and needle and comparable levels of antigen specific T-cells. Furthermore, the protective efficacy for the two vaccination methods was comparable and similar to BCG vaccination both six and 52 weeks after vaccination. These results therefore advocate the further development of the Bioneedle devises and applicators for the delivery of human vaccines.
    PLoS ONE 01/2010; 5(11):e15043. · 3.73 Impact Factor

Publication Stats

7k Citations
802.57 Total Impact Points

Institutions

  • 1999–2014
    • Statens Serum Institut
      • Department of Infectious Disease Immunology
      København, Capital Region, Denmark
    • Odense University Hospital
      • Molecular biology laboratory
      Odense, South Denmark, Denmark
  • 2013
    • Max Planck Institute for Infection Biology
      • Department of Immunology
      Berlín, Berlin, Germany
    • University of Copenhagen
      • Department of Pharmacy
      Copenhagen, Capital Region, Denmark
  • 2006–2013
    • Aston University
      • School of Life and Health Sciences
      Birmingham, ENG, United Kingdom
  • 2008–2012
    • University of Geneva
      • • Department of Pathology and Immunology (PATIM)
      • • Faculty of Medicine
      Genève, GE, Switzerland
  • 2011
    • University of Pittsburgh
      • Department of Pediatrics
      Pittsburgh, PA, United States
  • 2004–2011
    • Armauer Hansen Research Institute
      Ādīs Ābeba, Ādīs Ābeba, Ethiopia
  • 2003–2011
    • Leiden University Medical Centre
      • • Department of Infectious Diseases
      • • Department of Immunhematology and Blood Transfusion
      Leiden, South Holland, Netherlands
  • 2009
    • Aeras Global TB Vaccine Foundation
      Maryland, United States
  • 2007
    • University of Greifswald
      • Institute for Microbiology
      Greifswald, Mecklenburg-Vorpommern, Germany
  • 2005
    • Biomedical primate research centre
      • Parasitology
      Rijswijk, South Holland, Netherlands
  • 2004–2005
    • Copenhagen University Hospital Hvidovre
      • Department of Infectious Diseases
      Hvidovre, Capital Region, Denmark
  • 2002
    • Queen's University Belfast
      Béal Feirste, N Ireland, United Kingdom
    • University of Porto
      • Institute for Molecular and Cell Biology
      Oporto, Porto, Portugal