R W Compans

Emory University, Atlanta, Georgia, United States

Are you R W Compans?

Claim your profile

Publications (435)2116.96 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Prevention of seasonal influenza epidemics and pandemics relies on widespread vaccination coverage to induce protective immunity. In addition to a good antigenic match with the circulating viruses, the effectiveness of individual strains represented in the trivalent vaccines depends on their immunogenicity. In this study, we evaluated the immunogenicity of H1N1, H3N2, and B seasonal influenza virus vaccine strains delivered individually with a novel dissolving microneedle patch and the stability of this formulation during storage at 25 °C. Our data demonstrate that all strains retained their antigenic activity after incorporation in the dissolving patches as measured by single radial diffusion (SRID) assay and immune responses to vaccination in BALB/c mice. After a single immunization, all three antigens delivered with microneedle patches induced superior neutralizing antibody titers compared to intramuscular immunization. Cutaneous antigen delivery was especially beneficial for the less immunogenic B strain. Mice immunized with dissolving microneedle patches encapsulating influenza A/Brisbane/59/07 (H1N1) vaccine were fully protected against lethal challenge by homologous mouse-adapted influenza virus. All vaccine components retained activity during storage at room temperature for at least 3 months as measured in vitro by SRID assay and in vivo by mouse immunization studies. Our data demonstrate that dissolving microneedle patches are a promising advance for influenza cutaneous vaccination due to improved immune responses using less immunogenic influenza antigens and enhanced stability.
    04/2015; DOI:10.1007/s13346-015-0228-0
  • [Show abstract] [Hide abstract]
    ABSTRACT: In addition to its surface glycoprotein (GP), Ebola virus directs the production of large quantities of a truncated glycoprotein isoform (sGP) that is secreted into the extracellular space. We recently reported that sGP actively diverts host antibody responses against the epitopes that it shares with GP and thereby allows itself to absorb anti-GP antibodies, a phenomenon we termed "antigenic subversion." To investigate the effect of antigenic subversion by sGP on protection against virus infection, we compared immune responses induced by different prime-boost immunization regimens with GP and sGP DNA vaccines in mice and their efficacy against lethal Ebola virus challenge. Similar levels of anti-GP antibodies were induced by 2 immunizations with sGP and GP DNA vaccines. However, 2 immunizations with GP but not sGP DNA vaccine fully protected mice from lethal challenge. Boosting with sGP or GP DNA vaccine in mice that had been primed by GP or sGP DNA vaccine augmented the levels of anti-GP antibody responses and further improved protective efficacy against Ebola virus infection. These results show that both the quality and the levels of anti-GP antibody responses affect the efficacy of protection against Ebola virus infection. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
    The Journal of Infectious Diseases 04/2015; DOI:10.1093/infdis/jiv186 · 5.78 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Recombinant virus-like nanoparticles (VLPs) are a promising nanoparticle platform to develop safe vaccines for many viruses. Herein, we describe a novel and rapid protein transfer process to enhance the potency of enveloped VLPs by decorating influenza VLPs with exogenously added glycosylphosphatidylinositol-anchored immunostimulatory molecules (GPI-ISMs). With protein transfer, the level of GPI-ISM incorporation onto VLPs is controllable by varying incubation time and concentration of GPI-ISMs added. ISM incorporation was dependent upon the presence of a GPI-anchor and incorporated proteins were stable and functional for at least 4 weeks when stored at 4°C. Vaccinating mice with GPI-granulocyte macrophage colony-stimulating factor (GM-CSF)-incorporated-VLPs induced stronger antibody responses and better protection against a heterologous influenza virus challenge than unmodified VLPs. Thus, VLPs can be enriched with ISMs by protein transfer to increase the potency and breadth of the immune response, which has implications in developing effective nanoparticle-based vaccines against a broad spectrum of enveloped viruses. Copyright © 2015. Published by Elsevier Inc.
    Nanomedicine Nanotechnology Biology and Medicine 03/2015; 11(5). DOI:10.1016/j.nano.2015.02.008 · 5.98 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Skin has gained substantial attention as a vaccine target organ due to its immunological properties, which include a high density of professional antigen presenting cells (APCs). Previous studies have demonstrated the effectiveness of this vaccination route not only in animal models but also in adults. Young children represent a population group that is at high risk from influenza infection. As a result, this group could benefit significantly from influenza vaccine delivery approaches through the skin and the improved immune response it can induce. In this study, we compared the immune responses in young BALB/c mice upon skin delivery of influenza vaccine with vaccination by the conventional intramuscular route. Young mice that received 5μg of H1N1 A/Ca/07/09 influenza subunit vaccine using MN demonstrated an improved serum antibody response (IgG1 and IgG2a) when compared to the young IM group, accompanied by higher numbers of influenza-specific antibody secreting cells (ASCs) in the bone marrow. In addition, we observed increased activation of follicular helper T cells and formation of germinal centers in the regional lymph nodes in the MN immunized group, rapid clearance of the virus from their lungs as well as complete survival, compared with partial protection observed in the IM-vaccinated group. Our results support the hypothesis that influenza vaccine delivery through the skin would be beneficial for protecting the high-risk young population from influenza infection. Copyright © 2015. Published by Elsevier Ltd.
    Vaccine 03/2015; 57. DOI:10.1016/j.vaccine.2015.01.086 · 3.49 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Influenza virus is a source of significant health and economic burden from yearly epidemics and sporadic pandemics. Given the potential for the emerging H7N9 influenza virus to cause severe respiratory infections and the lack of exposure to H7 and N9 influenza viruses in the human population, we aimed to quantify the H7N9 cross-reactive memory T cell reservoir in humans and mice previously exposed to common circulating influenza viruses. We identified significant cross-reactive T cell populations in humans and mice; we also found that cross-reactive memory T cells afforded heterosubtypic protection by reducing morbidity and mortality upon lethal H7N9 challenge. In context with our observation that PR8-primed mice have limited humoral cross-reactivity with H7N9, our data suggest protection from H7N9 challenge is indeed mediated by cross-reactive T cell populations established upon previous priming with another influenza virus. Thus, pre-existing cross-reactive memory T cells may limit disease severity in the event of an H7N9 influenza virus pandemic.
    PLoS ONE 02/2015; 10(2):e0115725. DOI:10.1371/journal.pone.0115725 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The Ebola virus surface glycoprotein (GP1,2) mediates host cell attachment and fusion, and is the primary target for host neutralizing antibodies. Expression of GP1,2 at high levels disrupts normal cell physiology, and EBOV uses an RNA editing mechanism to regulate expression of the GP gene. In this study, we demonstrate that high levels of GP1,2 expression impair production and release of EBOV VLPs, as well as infectivity of GP1,2-pseudotyped viruses. We further show that this effect is mediated through two mechanisms. First, high levels of GP1,2 expression reduce synthesis of other proteins needed for virus assembly. Second, viruses containing high levels of GP1,2 are intrinsically less infectious, possibly due to impaired receptor binding or endosomal processing. Importantly, proteolysis can rescue the infectivity of high-GP1,2 containing viruses. Taken together, our findings indicate that GP1,2 expression levels have a profound effect on factors that contribute to virus fitness, and that RNA editing may be an important mechanism employed by EBOV to regulate GP1,2 expression in order to optimize virus production and infectivity.
    Journal of Virology 11/2014; 89(2). DOI:10.1128/JVI.01810-14 · 4.65 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Influenza virus H9N2 subtype has triggered co-infection with other infectious agents, resulting in huge economical losses in the poultry industry. Our current study aims to evaluate the antiviral activity of protocatechuic acid (PCA) against a virulent H9N2 strain in a mouse model. 120 BALB/c mice were divided into one control group, one untreated group, one 50 mg/kg amantadine hydrochloride-treated group and three PCA groups treated 12 hours post-inoculation with 40, 20 or 10 mg/kg PCA for 7 days. All the infected animals were inoculated intranasally with 0.2 ml of a A/Chicken/Hebei/4/2008(H9N2) inoculum. A significant body weight loss was found in the 20 mg/kg and 40 mg/kg PCA-treated and amantadine groups as compared to the control group. The 14 day survivals were 94.4%, 100% and 95% in the PCA-treated groups and 94.4% in the amantadine hydrochloride group, compared to less than 60% in the untreated group. Virus loads were less in the PCA-treated groups compared to the amantadine-treated or the untreated groups. Neutrophil cells in BALF were significantly decreased while IFN-γ, IL-2, TNF-α and IL-6 decreased significantly at days 7 in the PCA-treated groups compared to the untreated group. Furthermore, a significantly decreased CD4+/CD8+ ratio and an increased proportion of CD19 cells were observed in the PCA-treated groups and amantadine-treated group compared to the untreated group. Mice administered with PCA exhibited a higher survival rate and greater viral clearance associated with an inhibition of inflammatory cytokines and activation of CD8+ T cell subsets. PCA is a promising novel agent against bird flu infection in the poultry industry.
    PLoS ONE 10/2014; 9(10):e111004. DOI:10.1371/journal.pone.0111004 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Respiratory syncytial virus (RSV) is the most important pathogen for lower respiratory tract illness in infants and a high priority for vaccine development. We previously reported that RSV virus-like particles (VLPs) expressing either the fusion (F) or attachment (G) glycoprotein could confer protection against RSV challenge in BALB/c mice. Here, we tested the hypothesis that RSV VLP vaccine efficacy can be enhanced by mixing RSV VLP F and RSV VLP G, and we analyzed host responses to these RSV VLPs. Mice were immunized with VLP F, VLP G, or VLP F + VLP G. Lung viral loads in BALB/c mice following RSV strain A2-line19F challenge were lower in mice vaccinated with RSV VLP F + VLP G compared to VLP F- or VLP G-vaccinated mice. Vaccination with VLP F or VLP F + VLP G induced similar levels of neutralizing antibodies. The enhanced protection against RSV challenge induced by vaccination with RSV VLP F + VLP G correlated with CD8 T cells producing T helper type 1 cytokines. VLP G vaccination alone followed by challenge resulted in immunopathology similar to formalin-inactivated RSV vaccination and RSV challenge. Taken together, mixed VLP F + VLP G provided a high level of protection against RSV without vaccine-induced immunopathology, but VLP G vaccination enhanced disease when used alone.
    Antiviral Research 09/2014; 111. DOI:10.1016/j.antiviral.2014.09.005 · 3.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Detection of Immunoglobulin M (IgM) antibodies has long been used as an important diagnostic tool for identifying active viral infections, but their relevance in later stages has not been clearly defined in vivo. In this study we followed the kinetics, longevity and function of influenza virus-specific IgM antibodies following sub-lethal infection of mice with live mouse-adapted A/PR/8/34 virus or immunization with formalin-inactivated virus for two years. These groups mounted robust protective immune responses and survived lethal challenge with 50xLD50 mouse-adapted A/PR/8/34 virus 600 days after the primary exposure. Surprisingly, virus-specific IgM antibodies persisted along with IgG antibodies and we found a significantly higher number of IgM(+) virus-specific plasma cells than IgG(+) plasma cells that persisted for at least 9 months post-exposure. The IgM antibodies were functional as they neutralized influenza virus in the presence of complement just as well as IgG antibodies.
    Clinical and vaccine Immunology: CVI 08/2014; 21(11). DOI:10.1128/CVI.00374-14 · 2.37 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cutaneous vaccination with microneedle patches offers several advantages over more frequently used approaches for vaccine delivery, including improved protective immunity. However, the involvement of specific APC subsets and their contribution to the induction of immunity following cutaneous vaccine delivery is not well understood. A better understanding of the functions of individual APC subsets in the skin will allow us to target specific skin cell populations in order to further enhance vaccine efficacy. Here we use a Langerin-EGFP-DTR knock-in mouse model to determine the contribution of langerin(+) subsets of skin APCs in the induction of adaptive immune responses following cutaneous microneedle delivery of influenza vaccine. Depletion of langerin(+) cells prior to vaccination resulted in substantial impairment of both Th1 and Th2 responses, and decreased post-challenge survival rates, in mice vaccinated cutaneously but not in those vaccinated via the intramuscular route or in non-depleted control mice. Our results indicate that langerin(+) cells contribute significantly to the induction of protective immune responses following cutaneous vaccination with a subunit influenza vaccine.
    Scientific Reports 08/2014; 4:6094. DOI:10.1038/srep06094 · 5.58 Impact Factor
  • Ioanna Skountzou, Richard W Compans
    [Show abstract] [Hide abstract]
    ABSTRACT: Problems with existing influenza vaccines include the strain specificity of the immune response, resulting in the need for frequent reformulation in response to viral antigenic drift. Even in years when the same influenza strains are prevalent, the duration of immunityduration of immunity is limited, and results in the need for annual revaccination. The immunogenicity of the present split or subunit vaccines is also lower than that observed with whole inactivated virus, and the vaccines are not very effective in high risk groups such as the young or the elderly. Vaccine coverage is incomplete, due in part to concerns about the use of hypodermic needles for delivery. Alternative approaches for vaccination are being developed which address many of these concerns. Here we review new approaches which focus on skin immunization, including the development of needle-free delivery systems which use stable dry formulations and induce stronger and longer-lasting immune responses.
    Current topics in microbiology and immunology 07/2014; 386. DOI:10.1007/82_2014_407 · 3.47 Impact Factor
  • Source
    Han Zhang, Li Wang, Richard W Compans, Bao-Zhong Wang
    [Show abstract] [Hide abstract]
    ABSTRACT: Due to frequent viral antigenic change, current influenza vaccines need to be re-formulated annually to match the circulating strains for battling seasonal influenza epidemics. These vaccines are also ineffective in preventing occasional outbreaks of new influenza pandemic viruses. All these challenges call for the development of universal influenza vaccines capable of conferring broad cross-protection against multiple subtypes of influenza A viruses. Facilitated by the advancement in modern molecular biology, delicate antigen design becomes one of the most effective factors for fulfilling such goals. Conserved epitopes residing in virus surface proteins including influenza matrix protein 2 and the stalk domain of the hemagglutinin draw general interest for improved antigen design. The present review summarizes the recent progress in such endeavors and also covers the encouraging progress in integrated antigen/adjuvant delivery and controlled release technology that facilitate the development of an affordable universal influenza vaccine.
    Viruses 05/2014; 6(5):1974-1991. DOI:10.3390/v6051974 · 3.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Sporadic activity by H5N2 influenza viruses has been observed in chickens in Taiwan from 2003 to 2012. The available information suggests that these viruses were generated by reassortment between a Mexican-like H5N2 virus and a local enzootic H6N1 virus. Yet the origin, prevalence, and pathogenicity of these H5N2 viruses have not been fully defined. Following the 2012 highly pathogenic avian influenza (HPAI) outbreaks, surveillance was conducted from December 2012 to July 2013 at a live-poultry wholesale market in Taipei. Our findings showed that H5N2 and H6N1 viruses cocirculated at low levels in chickens in Taiwan. Phylogenetic analyses revealed that all H5N2 viruses had hemagglutinin (HA) and neuraminidase (NA) genes derived from a 1994 Mexican-like virus, while their internal gene complexes were incorporated from the enzootic H6N1 virus lineage by multiple reassortment events. Pathogenicity studies demonstrated heterogeneous results even though all tested viruses had motifs (R-X-K/R-R) supportive of high pathogenicity. Serological surveys for common subtypes of avian viruses confirmed the prevalence of the H5N2 and H6N1 viruses in chickens and revealed an extraordinarily high seroconversion rate to an H9N2 virus, a subtype that is not found in Taiwan but is prevalent in mainland China. These findings suggest that reassortant H5N2 viruses, together with H6N1 viruses, have become established and enzootic in chickens throughout Taiwan and that a large-scale vaccination program might have been conducted locally that likely led to the introduction of the 1994 Mexican-like virus to Taiwan in 2003.
    Journal of Virology 03/2014; DOI:10.1128/JVI.00139-14 · 4.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Current influenza vaccines do not provide good protection against antigenically different influenza A viruses. As an approach to overcome strain-specificity of protection, this study demonstrates significantly improved long-term cross protection by supplementing split vaccines with a conserved molecular target, a repeat of the influenza M2 ectodomain (M2e) expressed on virus-like particles (M2e5x VLPs) in a membrane-anchored form. Intramuscular immunization with H1N1 split vaccine (A/California/07/2009) supplemented with M2e5x VLPs induced M2e specific humoral and cellular immune responses, and shaped the host responses to the vaccine in the direction of T helper type 1 responses inducing dominant IgG2a isotype antibodies as well as IFN-? producing cells in systemic and mucosal sites. Upon lethal challenge, M2e5x VLP-supplemented vaccination lowered lung viral loads and induced long-term cross protection against H3N2 or H5N1 subtype influenza viruses over 12 months. M2e antibodies, CD4 T cells, and CD8 T-cells were found to contribute to improving heterosubtypic cross protection. In addition, improved cross protection by supplemented vaccination with M2e5x VLPs was mediated via Fc receptors. The results support evidence that supplementation with M2e5x VLPs is a promising approach for overcoming the limitation of strain-specific protection by current influenza vaccination.Molecular Therapy (2014); doi:10.1038/mt.2014.33.
    Molecular Therapy 03/2014; 22(7). DOI:10.1038/mt.2014.33 · 6.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The generation of memory B cells by vaccination plays a critical role in maintaining antigen specific antibodies and producing antibody responses upon re-exposure to a pathogen. B cell populations contributing to antibody production and protection by vaccination remain poorly defined. We used influenza virus-like particle (VLP) vaccine in a transgenic mouse model that would identify germinal center-derived memory B cells with the expression of yellow fluorescent protein (YFP+ cells). Immunization with influenza VLP vaccine did not induce significant increases in YFP+ cells although vaccine antigen-specific antibodies in sera were found to confer protection against a lethal dose of influenza A virus (A/PR8). In addition, CD43+B220- populations with low YFP+ cells mainly contributed to the production of vaccine antigen-specific IgG isotype-switched antibodies whereas CD43-B220+ populations with high YFP+ cells were able to produce vaccine antigen-specific IgM antibodies. Challenge infection of immunized transgenic mice with live influenza A virus resulted in significant increases in YFP+ cells in the B220- populations of spleen and bone marrow cells. These results suggest that CD43+B220- B cells generated by vaccination are important for producing influenza vaccine antigen-specific antibodies and conferring protection.This article is protected by copyright. All rights reserved.
    Immunology 03/2014; DOI:10.1111/imm.12287 · 3.74 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Most vaccines are administered by intramuscular injection using a hypodermic needle and syringe. Some limitations of this procedure include reluctance to be immunized because of fear of needlesticks, and concerns associated with the safe disposal of needles after their use. Skin delivery is an alternate route of vaccination that has potential to be painless and could even lead to dose reduction of vaccines. Recently, microneedles have emerged as a novel painless approach for delivery of influenza vaccines via the skin. Areas covered: In this review, we briefly summarize the approaches and devices used for skin vaccination, and then focus on studies of skin immunization with influenza vaccines using microneedles. We discuss both the functional immune response and the nature of this immune response following vaccination with microneedles. Expert opinion: The cutaneous administration of influenza vaccines using microneedles offers several advantages: it is painless, elicits stronger immune responses in preclinical studies and could improve responses in high-risk populations. These dry formulations of vaccines provide enhanced stability, a property of high importance in enabling their rapid global distribution in response to possible outbreaks of pandemic influenza and newly emerging infectious diseases.
    Expert Opinion on Drug Delivery 02/2014; DOI:10.1517/17425247.2014.885947 · 4.12 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Influenza vaccines with broad cross-protection are urgently needed to prevent an emerging influenza pandemic. A fusion protein of the TLR5-agonist domains from flagellin and multiple repeats of the conserved extracellular domain of the influenza matrix protein 2 (M2e) was constructed, purified and evaluated as such a vaccine. A painless vaccination method suitable for possible self-administration using coated microneedle arrays was investigated for skin-targeted delivery of the fusion protein in a mouse model. The results demonstrate that microneedle immunization induced strong humoral as well as mucosal antibody responses and conferred complete protection against homo- and heterosubtypic lethal virus challenges. Protective efficacy with microneedles was found to be significantly better than that seen with conventional intramuscular injection, and comparable to that observed with intranasal immunization. Because of its advantages for administration, safety and storage, microneedle delivery of M2e-flagellin fusion protein is a promising approach for an easy-to-administer universal influenza vaccine.
    Journal of Controlled Release 01/2014; 178. DOI:10.1016/j.jconrel.2014.01.002 · 7.26 Impact Factor
  • Sang-Moo Kang, Min-Chul Kim, Richard W Compans
    [Show abstract] [Hide abstract]
    ABSTRACT: Current influenza vaccines are primarily targeted to induce immunity to the influenza virus strain-specific hemagglutinin antigen and are not effective in controlling outbreaks of new pandemic viruses. An approach for developing universal vaccines is to present highly conserved antigenic epitopes in an immunogenic conformation such as virus-like particles (VLPs) together with an adjuvant to enhance the vaccine immunogenicity. In this review, the authors focus on conserved antigenic targets and molecular adjuvants that were presented in VLPs. Conserved antigenic targets that include the hemagglutinin stalk domain, the external domain of influenza M2 and neuraminidase are discussed in addition to molecular adjuvants that are engineered to be incorporated into VLPs in a membrane-anchored form.
    Expert Review of Vaccines 01/2014; 11(8). DOI:10.1586/erv.12.70 · 4.22 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract To find an effective mucosal adjuvant for influenza virus-like particles (VLPs), we compared the effects of known adjuvants Alum, CpG DNA, monophosphoryl lipid A (MPL), poly IC, gardiquimod, and cholera toxin (CT). Mice that were intranasally immunized with Alum, CpG, MPL, and CT adjuvanted VLPs showed higher levels of antibodies in both sera and mucosa. Hemagglutination inhibition and virus neutralizing activities were enhanced in groups adjuvanted with Alum, MPL, or CT. Influenza virus specific long-lived cells secreting IgG and IgA antibodies were found at high levels both in bone marrow and spleen in the Alum, CpG and CT adjuvanted groups. A similar level of protection was observed among different adjuvanted groups, except the CT adjuvant that showed a higher efficacy in lowering lung viral loads after challenge. Alum and CT adjuvants differentially increased influenza VLP-mediated activation of dendritic cells and splenocytes in vitro, supporting the in vivo pattern of antibody isotypes and cytokine production. These results suggest that Alum, MPL, or CpG adjuvants, which have been tested clinically, can be developed as an effective mucosal adjuvant for influenza VLP vaccines.
    Viral immunology 11/2013; DOI:10.1089/vim.2013.0013 · 1.64 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Miniaturized microneedle devices are being developed for painlessly targeting vaccines to the immune cell populations in skin. As skin immunization studies are generally restricted to animal models however, where skin architecture and immunity is greatly different to human, surprisingly little is known about the local human response to intradermal (ID) vaccines. Here we use surgically excised human skin to explore for the first time the complex molecular and cellular host responses to a candidate influenza vaccine comprising nanoparticulate virus-like-particles (VLPs), administered via conventional hypodermic injection or reduced scale microneedles. Responses at the molecular level are determined by microarray analysis (47,296 discrete transcripts) and validated by quantitative PCR (96 genes). Cellular response is probed through monitoring migration of dendritic cells in viable skin tissue. Gene expression mapping, ontological analysis and qPCR reveal up-regulation of a host of genes responsible for key immunomodulatory processes and host viral response, including cell recruitment, activation, migration and T cell interaction following both ID and microneedle injection of VLPs; the response from the microneedles being more subtle. Significant morphological and migratory changes to skin dendritic cells are also apparent following microneedle VLP delivery. This is the first study displaying the global, multifaceted immunological events that occur at the site of vaccine deposition in human skin and will subsequently influence the degree and nature of innate and adaptive immune responses. An increased understanding of the detailed similarities and differences in response against antigen administered via different delivery modalities will inform the development of improved vaccines and vaccine delivery systems.
    10/2013; 2(10). DOI:10.1002/adhm.201300006

Publication Stats

15k Citations
2,116.96 Total Impact Points

Institutions

  • 1994–2015
    • Emory University
      • • Department of Microbiology and Immunology
      • • Emory Vaccine Center
      Atlanta, Georgia, United States
    • St. Jude Children's Research Hospital
      • Department of Infectious Diseases
      Memphis, TN, United States
  • 2013
    • Kyung Hee University Medical Center
      Sŏul, Seoul, South Korea
  • 2012–2013
    • Erasmus MC
      • Department of Virology
      Rotterdam, South Holland, Netherlands
  • 2011
    • Osaka University
      • Department of Host Defense
      Suika, Ōsaka, Japan
  • 2010–2011
    • Georgia Institute of Technology
      • School of Chemical & Biomolecular Engineering
      Atlanta, Georgia, United States
  • 2009
    • Tulane University
      • Department of Microbiology and Immunology
      New Orleans, Louisiana, United States
  • 1977–2008
    • University of Alabama at Birmingham
      • Department of Microbiology
      Birmingham, Alabama, United States
  • 2006
    • University of Technology Munich
      • Institut für Medizinische Mikrobiologie, Immunologie und Hygiene
      München, Bavaria, Germany
  • 2003–2006
    • Baylor College of Medicine
      Houston, Texas, United States
  • 2005
    • Harbin Veterinary Research Institute
      Charbin, Heilongjiang Sheng, China
  • 2000
    • The University of Memphis
      • Department of Microbiology and Molecular Cell Sciences
      Memphis, Tennessee, United States
  • 1998
    • Leidos Biomedical Research
      Maryland, United States
    • Harvard University
      Cambridge, Massachusetts, United States
  • 1993
    • Philipps University of Marburg
      Marburg, Hesse, Germany
  • 1988–1991
    • Purdue University
      • Department of Biological Sciences
      ウェストラファイエット, Indiana, United States
    • University of Florida
      • Division of Infectious Diseases
      Gainesville, FL, United States
  • 1976–1981
    • University of Alabama Medical Center
      Birmingham, Alabama, United States
  • 1980
    • University of Alabama
      Tuscaloosa, Alabama, United States
  • 1966–1976
    • The Rockefeller University
      • Laboratory of Animal Behavior
      New York City, New York, United States
  • 1974
    • Memorial Sloan-Kettering Cancer Center
      New York, New York, United States
  • 1969
    • Australian National University
      Canberra, Australian Capital Territory, Australia