Scholars@Duke
Herman Ford Staats

Herman Ford Staats

Professor of Pathology
Pathology
herman.staats@duke.edu
Duke Box 3712, Durham, NC 27710
346M, Davison Building, Trent Drive, Durham, NC 27710

Selected Publications

Mastoparan-7 adjuvanted COBRA H1 and H3 hemagglutinin influenza vaccines.

Journal Article Sci Rep · June 14, 2024 Adjuvants enhance, prolong, and modulate immune responses by vaccine antigens to maximize protective immunity and enable more effective immunization in the young and elderly. Most adjuvants are formulated with injectable vaccines. However, an intranasal ro ... Full text Link to item Cite

Evaluation of repRNA vaccine for induction and in utero transfer of maternal antibodies in a pregnant rabbit model.

Journal Article Mol Ther · April 5, 2023 Mother-to-child transmission is a major route for infections in newborns. Vaccination in mothers to leverage the maternal immune system is a promising approach to vertically transfer protective immunity. During infectious disease outbreaks, such as the 201 ... Full text Link to item Cite

Delivery of small molecule mast cell activators for West Nile Virus vaccination using acetalated dextran microparticles.

Journal Article Int J Pharm · March 5, 2023 Recently, there has been increasing interest in the activation of mast cells to promote vaccine efficacy. Several mast cell activating (MCA) compounds have been reported such as M7 and Compound 48/80 (C48/80). While these MCAs have been proven to be effica ... Full text Link to item Cite

Development of a broadly active influenza intranasal vaccine adjuvanted with self-assembled particles composed of mastoparan-7 and CpG.

Journal Article Frontiers in immunology · January 2023 Currently licensed vaccine adjuvants offer limited mucosal immunity, which is needed to better combat respiratory infections such as influenza. Mast cells (MCs) are emerging as a target for a new class of mucosal vaccine adjuvants. Here, we developed and c ... Full text Cite

Cas13d knockdown of lung protease Ctsl prevents and treats SARS-CoV-2 infection.

Journal Article Nat Chem Biol · October 2022 SARS-CoV-2 entry into cells requires specific host proteases; however, no successful in vivo applications of host protease inhibitors have yet been reported for treatment of SARS-CoV-2 pathogenesis. Here we describe a chemically engineered nanosystem encap ... Full text Link to item Cite

Intranasal Immunization and Milk Collection in Studies of Maternal Immunization in New Zealand White Rabbits (Oryctolagus cuniculus).

Journal Article J Vis Exp · July 31, 2021 Due to similarities in placentation and antibody transfer with humans, rabbits are an excellent model of maternal immunization. Additional advantages of this research model are the ease of breeding and sample collection, relatively short gestation period, ... Full text Link to item Cite

Highly-loaded protein nanocarriers prepared by Flash NanoPrecipitation with hydrophobic ion pairing.

Journal Article Int J Pharm · May 15, 2021 The efficient encapsulation of therapeutic proteins into delivery vehicles, particularly without loss of function, remains a significant research hurdle. Typical liposomal formulations achieve drug loadings on the order of 3-5% and encapsulation efficienci ... Full text Link to item Cite

Nasal Immunization With Small Molecule Mast Cell Activators Enhance Immunity to Co-Administered Subunit Immunogens.

Journal Article Front Immunol · 2021 Mast cell activators are a novel class of mucosal vaccine adjuvants. The polymeric compound, Compound 48/80 (C48/80), and cationic peptide, Mastoparan 7 (M7) are mast cell activators that provide adjuvant activity when administered by the nasal route. Howe ... Full text Link to item Cite

Novel mucosal adjuvant, mastoparan-7, improves cocaine vaccine efficacy.

Journal Article NPJ Vaccines · February 5, 2020 Cocaine is one of the most potent and addictive psychostimulants known and there are no available pharmacotherapies to treat cocaine addiction. Here we describe a novel cocaine vaccine employing the mucosal adjuvant and mast cell-activating oligopeptide, m ... Full text Link to item Cite

Novel mucosal adjuvant, mastoparan-7, improves cocaine vaccine efficacy.

Journal Article NPJ Vaccines · 2020 Cocaine is one of the most potent and addictive psychostimulants known and there are no available pharmacotherapies to treat cocaine addiction. Here we describe a novel cocaine vaccine employing the mucosal adjuvant and mast cell-activating oligopeptide, m ... Full text Open Access Link to item Cite

Innate Immunity based Mucosal Modulators and Adjuvants

Chapter · 2020 The development of mucosally administered vaccines remains a goal of many researchers who desire to develop a needle-free method of immunization that can induce antigen-specific immune responses in both systemic and mucosal tissues. The coadministration of ... Full text Link to item Cite

Fecal IgA, Antigen Absorption, and Gut Microbiome Composition Are Associated With Food Antigen Sensitization in Genetically Susceptible Mice.

Journal Article Front Immunol · 2020 Food allergy is a potentially fatal disease affecting 8% of children and has become increasingly common in the past two decades. Despite the prevalence and severe nature of the disease, the mechanisms underlying sensitization remain to be further elucidate ... Full text Link to item Cite

Innate Immunity-Based Mucosal Modulators and Adjuvants

Chapter · September 15, 2019 The development of mucosally administered vaccines remains a goal of many researchers who desire to develop a needle-free method of immunization that can induce antigen-specific immune responses in both systemic and mucosal tissues. The coadministration of ... Link to item Cite

Mast Cells For the Control of Mucosal Immunity

Chapter · September 15, 2019 Mast cells (MCs) are gaining recognition as key initiators and coordinators of host inflammatory and immune responses to various microbial pathogens. Their presence in mucosal tissues and skin make them one of the first immune cells to make contact with in ... Link to item Cite

Optimized Mucosal Modified Vaccinia Virus Ankara Prime/Soluble gp120 Boost HIV Vaccination Regimen Induces Antibody Responses Similar to Those of an Intramuscular Regimen.

Journal Article J Virol · July 15, 2019 The benefits of mucosal vaccines over injected vaccines are difficult to ascertain, since mucosally administered vaccines often induce serum antibody responses of lower magnitude than those induced by injected vaccines. This study aimed to determine if muc ... Full text Link to item Cite

Identification of Novel Mast Cell Activators Using Cell-Based High-Throughput Screening.

Journal Article SLAS Discov · July 2019 Mast cells (MCs) are known to regulate innate and adaptive immunity. MC activators have recently been described as safe and effective vaccine adjuvants. Many currently known MC activators are inadequate for in vivo applications, however, and research on id ... Full text Link to item Cite

Bridging Vaccine-Induced HIV-1 Neutralizing and Effector Antibody Responses in Rabbit and Rhesus Macaque Animal Models.

Journal Article J Virol · May 15, 2019 Studies in animal models are essential prerequisites for clinical trials of candidate HIV vaccines. Small animals, such as rabbits, are used to evaluate promising strategies prior to further immunogenicity and efficacy testing in nonhuman primates. Our goa ... Full text Link to item Cite

Adjuvant-free intragastric sensitization to peanut promotes anaphylaxis in CC027/GeniUnc mice

Conference JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY · February 1, 2019 Link to item Cite

MRGPR-mediated activation of local mast cells clears cutaneous bacterial infection and protects against reinfection.

Journal Article Sci Adv · January 2019 Mast cells (MCs) are strategically distributed at barrier sites and prestore various immunocyte-recruiting cytokines, making them ideal targets for selective activation to treat peripheral infections. Here, we report that topical treatment with mastoparan, ... Full text Open Access Link to item Cite

Perivascular dendritic cells elicit anaphylaxis by relaying allergens to mast cells via microvesicles.

Journal Article Science · November 9, 2018 Anaphylactic reactions are triggered when allergens enter the blood circulation and activate immunoglobulin E (IgE)-sensitized mast cells (MCs), causing systemic discharge of prestored proinflammatory mediators. As MCs are extravascular, how they perceive ... Full text Link to item Cite

Bridging Vaccine-induced Antibody Responses in Rabbit and Rhesus Macaque Animal Models

Conference AIDS RESEARCH AND HUMAN RETROVIRUSES · October 1, 2018 Link to item Cite

Mast cell activators as novel immune regulators.

Journal Article Curr Opin Pharmacol · August 2018 Mast cells are an important cell type of the innate immune system that when activated, play a crucial role in generating protective innate host responses after bacterial and viral infection. Additionally, activated mast cells influence lymph node compositi ... Full text Link to item Cite

Effect of endotoxin and alum adjuvant vaccine on peanut allergy.

Journal Article J Allergy Clin Immunol · February 2018 Full text Link to item Cite

Softness makes it better.

Journal Article Nat Mater · February 2018 Full text Link to item Cite

Adjuvanted Immunotherapy Approaches for Peanut Allergy.

Journal Article Front Immunol · 2018 Food allergies are a growing public health concern with an estimated 8% of US children affected. Peanut allergies are also on the rise and often do not spontaneously resolve, leaving individuals at-risk for potentially life-threatening anaphylaxis througho ... Full text Link to item Cite

Assessing the satisfaction and burden within an academic animal care and use program.

Journal Article FASEB J · September 2017 Although animal research requires adherence to various regulations and standards, the manner in which compliance is maintained and the degree of additional constraints varies between institutions. Regulatory burden, particularly if institutionally imposed, ... Full text Link to item Cite

Modified Vaccinia Ankara Virus Vaccination Provides Long-Term Protection against Nasal Rabbitpox Virus Challenge.

Journal Article Clin Vaccine Immunol · July 2016 Modified vaccinia Ankara virus (MVA) is a smallpox vaccine candidate. This study was performed to determine if MVA vaccination provides long-term protection against rabbitpox virus (RPXV) challenge, an animal model of smallpox. Two doses of MVA provided 10 ... Full text Link to item Cite

Combined HIV-1 Envelope Systemic and Mucosal Immunization of Lactating Rhesus Monkeys Induces a Robust Immunoglobulin A Isotype B Cell Response in Breast Milk.

Journal Article J Virol · May 15, 2016 UNLABELLED: Maternal vaccination to induce anti-HIV immune factors in breast milk is a potential intervention to prevent postnatal HIV-1 mother-to-child transmission (MTCT). We previously demonstrated that immunization of lactating rhesus monkeys with a mo ... Full text Open Access Link to item Cite

Immunization with the Haemophilus ducreyi trimeric autotransporter adhesin DsrA with alum, CpG or imiquimod generates a persistent humoral immune response that recognizes the bacterial surface.

Journal Article Vaccine · February 24, 2016 The Ducreyi serum resistance A (DsrA) protein of Haemophilus ducreyi belongs to a large family of multifunctional outer membrane proteins termed trimeric autotransporter adhesins responsible for resistance to the bactericidal activity of human complement ( ... Full text Link to item Cite

Serological response following re-vaccination with Salmonella typhi Vi-capsular polysaccharide vaccines in healthy adult travellers.

Journal Article Vaccine · August 7, 2015 An injectable Vi-capsular polysaccharide vaccine against typhoid fever is available but vaccine-induced immunity tends to wane over time. The phenomenon of immunotolerance or hyporesponsiveness has earlier been described for polysaccharide vaccines such as ... Full text Link to item Cite

Effect of particulate adjuvant on the anthrax protective antigen dose required for effective nasal vaccination.

Journal Article Vaccine · July 17, 2015 Successful vaccine development is dependent on the development of effective adjuvants since the poor immunogenicity of modern subunit vaccines typically requires the use of potent adjuvants and high antigen doses. In recent years, adjuvant formulations com ... Full text Link to item Cite

Development of a novel adjuvanted nasal vaccine: C48/80 associated with chitosan nanoparticles as a path to enhance mucosal immunity.

Journal Article Eur J Pharm Biopharm · June 2015 In a time in which mucosal vaccines development has been delayed by the lack of safe and effective mucosal adjuvants, the combination of adjuvants has started to be explored as a strategy to obtain potent vaccine formulations. This study describes a novel ... Full text Link to item Cite

Scale of health: indices of safety and efficacy in the evolving environment of large biological datasets.

Journal Article Pharm Res · September 2014 The interdependent relationship between pharmacology and toxicology is fundamental to the concepts of efficacy and safety of both drugs and xenobiotics. The traditional concept of establishing efficacious and tolerated doses to define a 'therapeutic window ... Full text Link to item Cite

Intranasal mRNA nanoparticle vaccination induces prophylactic and therapeutic anti-tumor immunity.

Journal Article Sci Rep · June 4, 2014 Direct in vivo administration of messenger RNA (mRNA) delivered in both naked and nanoparticle formats are actively investigated because the use of dendritic cells transfected ex vivo with mRNA for cancer therapy is expensive and needs significant infrastr ... Full text Link to item Cite

Which comes first: the antigen or the adjuvant?

Journal Article J Clin Invest · June 2014 Recent attempts to develop an HIV-1 vaccine indicate that viral replication can be limited by the induction of viral-specific T cell responses; however, recent trials of vaccine candidates designed to target CD8+ T cell responses were unsuccessful. In this ... Full text Link to item Cite

Genomic correlates of variability in immune response to an oral cholera vaccine

Journal Article Nature · January 1, 2014 Cholera is endemic to many countries. Recent major outbreaks of cholera have prompted World Health Organization to recommend oral cholera vaccination as a public-health strategy. Variation in percentage of seroconversion upon cholera vaccination has been r ... Cite

Nasal dry powder vaccine delivery technology

Chapter · January 1, 2014 Nasal delivery of vaccines occurred over a millennium ago in China, where ground scabs from small pox lesions, presumably containing live virus, were sniffed. This practice was the basis for early vaccination with live virus in Europe in the eighteenth cen ... Full text Cite

Salmonella typhimurium impedes innate immunity with a mast-cell-suppressing protein tyrosine phosphatase, SptP.

Journal Article Immunity · December 12, 2013 The virulence of Salmonella is linked to its invasive capacity and suppression of adaptive immunity. This does not explain, however, the rapid dissemination of the pathogen after it breaches the gut. In our study, S. Typhimurium suppressed degranulation of ... Full text Link to item Cite

A mastoparan-derived peptide has broad-spectrum antiviral activity against enveloped viruses.

Journal Article Peptides · October 2013 Broad-spectrum antiviral drugs are urgently needed to treat individuals infected with new and re-emerging viruses, or with viruses that have developed resistance to antiviral therapies. Mammalian natural host defense peptides (mNHP) are short, usually cati ... Full text Link to item Cite

Genomic correlates of variability in immune response to an oral cholera vaccine.

Journal Article Eur J Hum Genet · September 2013 Cholera is endemic to many countries. Recent major outbreaks of cholera have prompted World Health Organization to recommend oral cholera vaccination as a public-health strategy. Variation in percentage of seroconversion upon cholera vaccination has been r ... Full text Link to item Cite

Evaluation of vaccine-induced antibody responses: impact of new technologies.

Journal Article Vaccine · June 7, 2013 Host response to vaccination has historically been evaluated based on a change in antibody titer that compares the post-vaccination titer to the pre-vaccination titer. A four-fold or greater increase in antigen-specific antibody has been interpreted to ind ... Full text Link to item Cite

Mucosal immunization of lactating female rhesus monkeys with a transmitted/founder HIV-1 envelope induces strong Env-specific IgA antibody responses in breast milk.

Journal Article J Virol · June 2013 We previously demonstrated that vaccination of lactating rhesus monkeys with a DNA prime/vector boost strategy induces strong T-cell responses but limited envelope (Env)-specific humoral responses in breast milk. To improve vaccine-elicited antibody respon ... Full text Link to item Cite

A comparison of non-toxin vaccine adjuvants for their ability to enhance the immunogenicity of nasally-administered anthrax recombinant protective antigen.

Journal Article Vaccine · March 1, 2013 Development of nasal immunization for human use is hindered by the lack of acceptable adjuvants. Although CT is an effective adjuvant, its toxicity will likely prevent its use in nasal vaccines. This study compared non-toxin adjuvants to CT for their abili ... Full text Link to item Cite

A Mast Cell Degranulation Screening Assay for the Identification of Novel Mast Cell Activating Agents.

Journal Article Medchemcomm · January 1, 2013 The development and use of vaccines and their ability to prevent infection/disease is a shining example of the benefit of biomedical research. Modern vaccines often utilize subunit immunogens that exhibit minimal immunogenicity and require the use of adjuv ... Full text Link to item Cite

Increased peanut-specific IgA levels in saliva correlate with food challenge outcomes after peanut sublingual immunotherapy.

Journal Article J Allergy Clin Immunol · April 2012 Peanut-specific IgA in saliva correlates with DBPCFC outcomes following peanut SLIT, suggesting that peanut-specific salivary IgA may be a potential biomarker for SLIT used to treat peanut allergy. ... Full text Link to item Cite

Maximal adjuvant activity of nasally delivered IL-1α requires adjuvant-responsive CD11c(+) cells and does not correlate with adjuvant-induced in vivo cytokine production.

Journal Article J Immunol · March 15, 2012 IL-1 has been shown to have strong mucosal adjuvant activities, but little is known about its mechanism of action. We vaccinated IL-1R1 bone marrow (BM) chimeric mice to determine whether IL-1R1 expression on stromal cells or hematopoietic cells was suffic ... Full text Link to item Cite

Synthetic mast-cell granules as adjuvants to promote and polarize immunity in lymph nodes.

Journal Article Nat Mater · January 22, 2012 Granules of mast cells (MCs) enhance adaptive immunity when, on activation, they are released as stable particles. Here we show that submicrometre particles modelled after MC granules augment immunity when used as adjuvants in vaccines. The synthetic parti ... Full text Link to item Cite

Stable dry powder formulation for nasal delivery of anthrax vaccine.

Journal Article J Pharm Sci · January 2012 There is a current biodefense interest in protection against anthrax. Here, we developed a new generation of stable and effective anthrax vaccine. We studied the immune response elicited by recombinant protective antigen (rPA) delivered intranasally with a ... Full text Link to item Cite

Dry powder vaccines for mucosal administration: critical factors in manufacture and delivery.

Journal Article Curr Top Microbiol Immunol · 2012 Dry powder vaccine formulations have proved effective for induction of systemic and mucosal immune responses. Here we review the use of dry vaccines for immunization in the respiratory tract. We discuss techniques for powder formulation, manufacture, chara ... Full text Link to item Cite

Scarcity or absence of humoral immune responses in the plasma and cervicovaginal lavage fluids of heavily HIV-1-exposed but persistently seronegative women.

Journal Article AIDS Res Hum Retroviruses · May 2011 To address an existing controversy concerning the presence of HIV-1-specific antibodies of the IgA isotype in the female genital tract secretions of highly-exposed but persistently seronegative (HEPSN) women, 41 samples of plasma and cervicovaginal lavage ... Full text Link to item Cite

Mucosal targeting of a BoNT/A subunit vaccine adjuvanted with a mast cell activator enhances induction of BoNT/A neutralizing antibodies in rabbits.

Journal Article PLoS One · January 27, 2011 BACKGROUND: We previously reported that the immunogenicity of Hcβtre, a botulinum neurotoxin A (BoNT/A) immunogen, was enhanced by fusion to an epithelial cell binding domain, Ad2F, when nasally delivered to mice with cholera toxin (CT). This study was per ... Full text Link to item Cite

Cytokines: the future of intranasal vaccine adjuvants.

Journal Article Clin Dev Immunol · 2011 Due to its potential as an effective, needle-free route of immunization for use with subunit vaccines, nasal immunization continues to be evaluated as a route of immunization in both research and clinical studies. However, as with other vaccination routes, ... Full text Link to item Cite

Effective induction of protective systemic immunity with nasally administered vaccines adjuvanted with IL-1.

Journal Article Vaccine · October 4, 2010 Featured Publication IL-1α and IL-1β were evaluated for their ability to provide adjuvant activity for the induction of serum antibody responses when nasally administered with protein antigens in mice and rabbits. In mice, intranasal (i.n.) immunization with pneumococcal surfa ... Full text Link to item Cite

Immunization with the Haemophilus ducreyi hemoglobin receptor HgbA with adjuvant monophosphoryl lipid A protects swine from a homologous but not a heterologous challenge.

Journal Article Infect Immun · September 2010 Haemophilus ducreyi, the etiological agent of chancroid, has a strict requirement for heme, which it acquires from its only natural host, humans. Previously, we showed that a vaccine preparation containing the native hemoglobin receptor HgbA purified from ... Full text Link to item Cite

Adenovirus F protein as a delivery vehicle for botulinum B.

Journal Article BMC Immunol · July 7, 2010 Featured Publication BACKGROUND: Immunization with recombinant carboxyl-terminal domain of the heavy chain (Hc domain) of botulinum neurotoxin (BoNT) stimulates protective immunity against native BoNT challenge. Most studies developing a botulism vaccine have focused on the wh ... Full text Open Access Link to item Cite

Polymer hydrogels: Chaperoning vaccines.

Journal Article Nat Mater · July 2010 Featured Publication Full text Link to item Cite

Development of a bead immunoassay to measure Vi polysaccharide-specific serum IgG after vaccination with the Salmonella enterica serovar Typhi Vi polysaccharide.

Journal Article Clin Vaccine Immunol · March 2010 Featured Publication Vi polysaccharide from Salmonella enterica serotype Typhi is used as one of the available vaccines to prevent typhoid fever. Measurement of Vi-specific serum antibodies after vaccination with Vi polysaccharide by enzyme-linked immunosorbent assay (ELISA) m ... Full text Link to item Cite

An In Vitro Model of Mast Cell Desensitization

Conference Journal of Allergy and Clinical Immunology · February 2010 Full text Cite

Genetic determinants of immune-response to a polysaccharide vaccine for typhoid.

Journal Article Hugo J · December 2009 UNLABELLED: Differences in immunological response among vaccine recipients are determined both by their genetic differences and environmental factors. Knowledge of genetic determinants of immunological response to a vaccine can be used to design a vaccine ... Full text Link to item Cite

Mast cell activator as a mucosal adjuvant in intranasal pertussis vaccine

Conference CLINICAL AND EXPERIMENTAL ALLERGY · December 1, 2009 Link to item Cite

Mast cell-derived particles deliver peripheral signals to remote lymph nodes.

Journal Article J Exp Med · October 26, 2009 Featured Publication During infection, signals from the periphery are known to reach draining lymph nodes (DLNs), but how these molecules, such as inflammatory cytokines, traverse the significant distances involved without dilution or degradation remains unclear. We show that ... Full text Link to item Cite

Mast cells augment adaptive immunity by orchestrating dendritic cell trafficking through infected tissues.

Journal Article Cell Host Microbe · October 22, 2009 Featured Publication Mast cells (MCs) are best known for eliciting harmful reactions, mostly after primary immunity has been established. Here, we report that, during footpad infection with E. coli in MC-deficient mice, as compared to their MC-sufficient counterparts, the seru ... Full text Link to item Cite

The mast cell activator compound 48/80 is safe and effective when used as an adjuvant for intradermal immunization with Bacillus anthracis protective antigen.

Journal Article Vaccine · June 2, 2009 Featured Publication We evaluated the safety and efficacy of the mast cell activator compound 48/80 (C48/80) when used as an adjuvant delivered intradermally (ID) with recombinant anthrax protective antigen (rPA) in comparison with two well-known adjuvants. Mice were vaccinate ... Full text Link to item Cite

Use of a Mast Cell Activator as a Mucosal Adjuvant for Pertussis Vaccines

Journal Article Journal of Allergy and Clinical Immunology · February 2009 Full text Cite

Identification of recombinant antibodies against multiple distinct toll-like receptors by homolog mining a single immune scFv phage library.

Journal Article J Immunol Methods · January 30, 2009 The generation of recombinant single-chain antibodies from either non-immune or immune phage display antibody libraries is an effective means to obtain high affinity antibodies against a specific target. Non-immune libraries contain a wide variety of antib ... Full text Link to item Cite

The contribution of type I interferon signaling to immunity induced by alphavirus replicon vaccines.

Journal Article Vaccine · September 15, 2008 Featured Publication The type I interferon (IFN) system is critical for protecting the mammalian host from numerous virus infections and plays a key role in shaping the antiviral adaptive immune response. In this report, the importance of type I IFN signaling was assessed in a ... Full text Link to item Cite

Alphavirus replicon particles acting as adjuvants promote CD8+ T cell responses to co-delivered antigen.

Journal Article Vaccine · August 5, 2008 Featured Publication Alphavirus replicon particles induce strong antibody and CD8+ T cell responses to expressed antigens in numerous experimental systems. We have recently demonstrated that Venezuelan equine encephalitis virus replicon particles (VRP) possess adjuvant activit ... Full text Link to item Cite

Nonmucosal alphavirus vaccination stimulates a mucosal inductive environment in the peripheral draining lymph node.

Journal Article J Immunol · July 1, 2008 Featured Publication The strongest mucosal immune responses are induced following mucosal Ag delivery and processing in the mucosal lymphoid tissues, and much is known regarding the immunological parameters which regulate immune induction via this pathway. Recently, experiment ... Full text Link to item Cite

An entirely cell-based system to generate single-chain antibodies against cell surface receptors.

Journal Article J Mol Biol · May 30, 2008 The generation of recombinant antibodies (Abs) using phage display is a proven method to obtain a large variety of Abs that bind with high affinity to a given antigen. Traditionally, the generation of single-chain Abs depends on the use of recombinant prot ... Full text Link to item Cite

Mast cell activators: a new class of highly effective vaccine adjuvants.

Journal Article Nat Med · May 2008 Featured Publication Mast cells (MCs) have recently received recognition as prominent effectors in the regulation of immune cell migration to draining lymph nodes and lymphocyte activation. However, their role in the development of humoral immune responses is not clear. Here, ... Full text Link to item Cite

In vitro and in vivo characterization of anthrax anti-protective antigen and anti-lethal factor monoclonal antibodies after passive transfer in a mouse lethal toxin challenge model to define correlates of immunity.

Journal Article Infect Immun · November 2007 Featured Publication Passive transfer of antibody may be useful for preexposure prophylaxis against biological agents used as weapons of terror, such as Bacillus anthracis. Studies were performed to evaluate the ability of anthrax antiprotective antigen (anti-PA) and antiletha ... Full text Link to item Cite

Novel dry powder preparations of whole inactivated influenza virus for nasal vaccination.

Journal Article AAPS PharmSciTech · October 12, 2007 Featured Publication The purpose of these studies was to enhance mucosal and systemic antibody production in response to increased local residence time of a whole inactivated influenza virus administered as a dry powder nasal vaccine formulation. Spray-freeze-drying (SFD) part ... Full text Link to item Cite

Mast cells enable heightened humoral immunity during infection

Journal Article JOURNAL OF IMMUNOLOGY · April 1, 2007 Link to item Cite

Mucosal vaccine development for botulinum intoxication.

Journal Article Expert Rev Vaccines · February 2007 Featured Publication Botulism has classically been considered to be a food- and water-borne disease. However, it was recently classified by the US National Institute of Allergy and Infectious Diseases (National Institute of Health) and the US Centers for Disease Control and Pr ... Full text Link to item Cite

Oral immunogenicity of the plant proteinase bromelain.

Journal Article Int Immunopharmacol · December 20, 2006 Bromelain is a natural mixture of proteolytic enzymes derived from pineapple stem that has been shown to have anti-inflammatory activity when administered orally. Although most proteins given orally without adjuvant (e.g., food) result in tolerance, we pre ... Full text Link to item Cite

Generation of mucosal anti-human immunodeficiency virus type 1 T-cell responses by recombinant Mycobacterium smegmatis.

Journal Article Clin Vaccine Immunol · November 2006 Featured Publication A successful vaccine vector for human immunodeficiency virus type 1 (HIV-1) should induce anti-HIV-1 immune responses at mucosal sites. We have generated recombinant Mycobacterium smegmatis vectors that express the HIV-1 group M consensus envelope protein ... Full text Link to item Cite

Mucosal vaccine targeting improves onset of mucosal and systemic immunity to botulinum neurotoxin A.

Journal Article J Immunol · October 15, 2006 Featured Publication Absence of suitable mucosal adjuvants for humans prompted us to consider alternative vaccine designs for mucosal immunization. Because adenovirus is adept in binding to the respiratory epithelium, we tested the adenovirus 2 fiber protein (Ad2F) as a potent ... Full text Link to item Cite

Capric acid and hydroxypropylmethylcellulose increase the immunogenicity of nasally administered peptide vaccines.

Journal Article AIDS Res Hum Retroviruses · June 2006 Featured Publication Immunization by the nasal route is an established method for the induction of mucosal and systemic humoral and cell-mediated antigen-specific responses. However, the effectiveness of nasal immunization is often hampered by the need for increased doses of a ... Full text Link to item Cite

Mucosal and systemic adjuvant activity of alphavirus replicon particles.

Journal Article Proc Natl Acad Sci U S A · March 7, 2006 Featured Publication Vaccination represents the most effective control measure in the fight against infectious diseases. Local mucosal immune responses are critical for protection from, and resolution of, infection by numerous mucosal pathogens. Antigen processing across mucos ... Full text Link to item Cite

CD4+CD25high T Regulatory Cells in Egg-Allergic Children Undergoing Oral Desensitization

Conference Journal of Allergy and Clinical Immunology · February 2006 Full text Cite

Cardiolipin polyspecific autoreactivity in two broadly neutralizing HIV-1 antibodies.

Journal Article Science · June 24, 2005 Featured Publication The design of a human immunodeficiency virus-1 (HIV-1) immunogen that can induce broadly reactive neutralizing antibodies is a major goal of HIV-1 vaccine development. Although rare human monoclonal antibodies (mAbs) exist that broadly neutralize HIV-1, HI ... Full text Link to item Cite

A novel neurotoxoid vaccine prevents mucosal botulism.

Journal Article J Immunol · February 15, 2005 Featured Publication The threat posed by botulism, classically a food- and waterborne disease with a high morbidity and mortality, has increased exponentially in an age of bioterrorism. Because botulinum neurotoxin (BoNT) could be easily disseminated by terrorists using an aer ... Full text Link to item Cite

Nasal peptide vaccination elicits CD8 responses and reduces viral burden after challenge with virulent murine cytomegalovirus.

Journal Article Microbiol Immunol · 2005 Infection of BALB/c mice with murine cytomegalovirus (MCMV) leads to CD8 cell responses to an immunodominant epitope YPHFMPTNL. We presented this epitope as a nasal peptide vaccine in combination with cholera toxin adjuvant, and evaluated immune responses ... Full text Link to item Cite

Gender differences in human immunodeficiency virus type 1-specific CD8 responses in the reproductive tract and colon following nasal peptide priming and modified vaccinia virus Ankara boosting.

Journal Article J Virol · December 2004 Featured Publication Induction of mucosal anti-human immunodeficiency virus type 1 (HIV-1) T-cell responses in males and females will be important for the development of a successful HIV-1 vaccine. An HIV-1 envelope peptide, DNA plasmid, and recombinant modified vaccinia virus ... Full text Link to item Cite

A comparative evaluation of nasal and parenteral vaccine adjuvants to elicit systemic and mucosal HIV-1 peptide-specific humoral immune responses in cynomolgus macaques.

Journal Article Vaccine · September 9, 2004 Featured Publication Cynomolgus macaques were immunized by either the intramuscular (i.m.) or intranasal (i.n.) route with a HIV-1 peptide-based immunogen (C4-V3 89.6P) alone, or formulated with novel adjuvants to evaluate the ability of the adjuvants to augment peptide-specif ... Full text Link to item Cite

Non-replicating mucosal and systemic vaccines: quantitative and qualitative differences in the Ag-specific CD8(+) T cell population in different tissues.

Journal Article Vaccine · March 29, 2004 Featured Publication Directed dissemination of Ag-specific CD8(+) T cells to infected organs or cancerous tissues is a prerequisite for optimal immunotherapy. Ag-specific CD8(+) T cells were quantitated in systemic and mucosal tissues after nasal, rectal, or cutaneous immuniza ... Full text Link to item Cite

Mast cell-derived tumor necrosis factor induces hypertrophy of draining lymph nodes during infection.

Journal Article Nat Immunol · December 2003 Featured Publication Palpable swelling of regional lymph nodes is a common sequela of microbial infections but the mechanism responsible for the sequestration and subsequent coordination of lymphocyte responses within these dynamic structures remains poorly understood. Here we ... Full text Link to item Cite

Prolonged CD4+ cell/virus load discordance during treatment with protease inhibitor-based highly active antiretroviral therapy: immune response and viral control.

Journal Article J Infect Dis · April 1, 2003 Mechanisms that underly discordant CD4+ cell/virus load (VL) responses in patients who receive highly active antiretroviral therapy (HAART) were studied in 30 human immunodeficiency virus (HIV)-positive patients, in 3 groups. Discordant responders maintain ... Full text Link to item Cite

Detection of mucosal antibodies in HIV type 1-infected individuals.

Journal Article AIDS Res Hum Retroviruses · November 20, 2002 HIV-1-specific mucosal IgA antibodies may correlate with protection in highly exposed but uninfected individuals, but have been detected at highly variable levels in HIV-1-infected individuals. To determine the best assays for detection of IgA antibodies i ... Full text Link to item Cite

Increased immunogenicity of HIV envelope subunit complexed with alpha2-macroglobulin when combined with monophosphoryl lipid A and GM-CSF.

Journal Article Vaccine · May 22, 2002 Critical to the success of HIV-1 subunit vaccines is the development of strategies to augment vaccine immunogenicity. Successful adjuvants must not only improve immunogenicity above current adjuvant levels, but must also decrease the dose of immunogen requ ... Full text Link to item Cite

Cytokines as adjuvants for the induction of anti-human immunodeficiency virus peptide immunoglobulin G (IgG) and IgA antibodies in serum and mucosal secretions after nasal immunization.

Journal Article J Virol · January 2002 Featured Publication Safe and potent new adjuvants are needed for vaccines that are administered to mucosal surfaces. This study was performed to determine if interleukin-1alpha (IL-1alpha) combined with other proinflammatory cytokines provided mucosal adjuvant activity for in ... Full text Link to item Cite

Cytokine requirements for induction of systemic and mucosal CTL after nasal immunization.

Journal Article J Immunol · November 1, 2001 Featured Publication Cholera toxin (CT) is frequently used as an experimental adjuvant intranasally for the induction of systemic and mucosal immunity. However, CT is highly reactogenic and not approved for use in humans. To define the cytokine requirements for the nasal activ ... Full text Link to item Cite

Human nasopharyngeal-associated lymphoreticular tissues. Functional analysis of subepithelial and intraepithelial B and T cells from adenoids and tonsils.

Journal Article Am J Pathol · December 2000 Subepithelial and intraepithelial lymphocytes of human adenoids and tonsils were characterized and directly compared to determine the potential contribution of these tissues to mucosal and systemic immune responses. The distribution of T and B cell subsets ... Full text Link to item Cite

Role of macrophages in restricting herpes simplex virus type 1 growth after ocular infection.

Journal Article Invest Ophthalmol Vis Sci · May 2000 PURPOSE: To investigate the role macrophages play in controlling herpes simplex virus (HSV)-1 replication after infection of the murine cornea. METHODS: Macrophage depletion in selected tissues before or after virus infection was achieved by repeated subco ... Link to item Cite

Altered immune responses in apolipoprotein E-deficient mice.

Journal Article J Lipid Res · April 2000 Apolipoprotein E (apoE) is a 34 kDa glycosylated protein with multiple biological properties. In addition to its role in cholesterol transport, apoE has in vitro immunomodulatory properties. Recent data suggest that these immunomodulatory effects of apoE m ... Link to item Cite

HIV vaccine development at Duke University Medical Center.

Journal Article Immunol Res · 2000 With the AIDS epidemic continuing to spread throughout the world, development of a safe, practical, and effective HIV vaccine is a national priority. HIV vaccine research efforts are currently targeted towards design of HIV immunogens that induce both cell ... Full text Link to item Cite

IL-1 is an effective adjuvant for mucosal and systemic immune responses when coadministered with protein immunogens.

Journal Article J Immunol · May 15, 1999 Featured Publication Mucosal immunization with soluble protein Ag alone may induce Ag-specific tolerance, whereas mucosal immunization with Ag in the presence of a mucosal adjuvant may induce Ag-specific systemic and mucosal humoral and cell-mediated immune responses. The most ... Link to item Cite

Mucosal adjuvanticity of interleukin

Journal Article FASEB JOURNAL · March 12, 1999 Link to item Cite

Intranasal immunization with cytotoxic T-lymphocyte epitope peptide and mucosal adjuvant cholera toxin: selective augmentation of peptide-presenting dendritic cells in nasal mucosa-associated lymphoid tissue.

Journal Article Infect Immun · December 1998 Featured Publication We previously reported that cholera toxin (CT) was required as a mucosal adjuvant for the induction of peptide-specific cytotoxic T lymphocytes (CTL) following intranasal immunization with CTL epitope peptides (A. Porgador et al., J. Immunol. 158:834-841, ... Full text Link to item Cite

Immunologic characterization of CD7-deficient mice.

Journal Article J Immunol · June 15, 1998 Human CD7 is an Ig superfamily molecule that is expressed on mature T and NK lymphocytes. Although in vitro studies have suggested a role for CD7 in lymphoid development and function, the exact function of CD7 in vivo has remained elusive. One patient has ... Link to item Cite

Intranasal immunization is superior to vaginal, gastric, or rectal immunization for the induction of systemic and mucosal anti-HIV antibody responses.

Journal Article AIDS Res Hum Retroviruses · July 20, 1997 Featured Publication Vaginal anti-HIV antibody responses may be beneficial, and possibly required, for vaccine-induced protection against HIV infection acquired through receptive vaginal intercourse. We have previously determined that intranasal immunization with a hybrid HIV ... Full text Link to item Cite

Intranasal immunization with CTL epitope peptides from HIV-1 or ovalbumin and the mucosal adjuvant cholera toxin induces peptide-specific CTLs and protection against tumor development in vivo.

Journal Article J Immunol · January 15, 1997 Featured Publication To evaluate the ability of mucosal immunization protocols using peptide immunogens to induce CTL responses, BALB/c and C57BL/6 mice were immunized intranasally (i.n.) with peptides corresponding to a known CTL epitope in HIV-1 glycoprotein 120 or OVA, resp ... Link to item Cite

Induction of cytotoxic T lymphocytes (CTL) specific for HIV-1 or protection against tumor challenge by intranasal immunization with CTL peptide and cholera toxin

Journal Article FASEB Journal · December 1, 1996 To evaluate mucosal routes of immunization for the induction of HIV-1 specific CTL, BALB/c mice were intranasally (IN) immunized with octameric peptides corresponding to a defined CTL epitope in HIV-1 gp120 (R10I) and the mucosal adjuvant cholera toxin (CT ... Cite

The V3 domain of SIVmac251 gp120 contains a linear neutralizing epitope.

Journal Article Virology · October 15, 1996 Antisera to 21 synthetic peptides containing hydrophilic sequences of simian immunodeficiency virus strain mac251 (SIVmac251) gp120 and gp32 were tested for the ability to neutralize SIVmac251. Goat antisera raised to peptides SP-1 and SP-1V containing the ... Full text Link to item Cite

Mucosal immunity to HIV-1: systemic and vaginal antibody responses after intranasal immunization with the HIV-1 C4/V3 peptide T1SP10 MN(A).

Journal Article J Immunol · July 1, 1996 Featured Publication To optimize mucosal immune responses to the HIV-1 peptide vaccine candidate T1SP10 MN(A), we intranasally immunized BALB/c and C57BL/6 mice with C4/V3 HIV-1 peptide together with the mucosal adjuvant cholera toxin (CT). Four doses over a 4-wk period result ... Link to item Cite

Epitope maps of the Escherichia coli heat-labile toxin B subunit for development of a synthetic oral vaccine.

Journal Article Infect Immun · April 1996 Linear B- and T-cell epitopes spanning all 103 amino acids of the Escherichia coli heat-labile toxin B subunit (LT-B) were assessed in mice orally immunized with native LT or with recombinant Salmonella enteritidis expressing LT-B. Oral administration of n ... Full text Link to item Cite

Regulation of mucosal and systemic antibody responses by T helper cell subsets, macrophages, and derived cytokines following oral immunization with live recombinant Salmonella.

Journal Article J Immunol · February 15, 1996 We have assessed regulatory Th cell and cytokine responses in mice after oral immunization with recombinant Salmonella (BRD 847) expressing fragment C of tetanus toxoid, since little information is available to explain how these vectors induce mucosal IgA ... Link to item Cite

Initial characterization of cd7 deficient mice: evidence of a role for CD7 in regulation of thymocyte development

Journal Article Journal of Investigative Medicine · January 1, 1996 Human CD7 is a 40 kilodalton member of the immunoglobulin gene superfamily that is expressed early in natural killer and T lymphocyte development. Although CD7 involvement in lymphocyte activation has been suggested by numerous studies, the functional role ... Cite

Mucosal adjuvant effect of cholera toxin in mice results from induction of T helper 2 (Th2) cells and IL-4.

Journal Article J Immunol · November 15, 1995 Despite pathophysiologic effects including diarrhea, cholera toxin (CT) is a potent mucosal immunogen and adjuvant. We investigated the influence of CT on T helper (Th)-type 1 (Th1) and Th2 cell-regulated Ag-specific B cell isotype and IgG subclass Ab resp ... Link to item Cite

Effect of bismuth salts on systemic and mucosal immune responses to orally administered cholera toxin.

Journal Article Immunopharmacology · November 1995 While the antimicrobial and antisecretory effects of bismuth salts are well documented, little is known regarding their effects on immune responses to enterotoxins such as that of V. cholerae or to orally administered vaccine antigens. To evaluate the effe ... Full text Link to item Cite

Oral vaccine models: multiple delivery systems employing tetanus toxoid.

Journal Article Ann N Y Acad Sci · August 15, 1994 We have not yet directly examined the Th cell responses induced by using Salmonella/BRD 847 as a vector nor have we performed these experiments following immunization with microspheres. However, production of high serum levels of antigen-specific IgG1 may ... Full text Link to item Cite

Helper Th1 and Th2 cell responses following mucosal or systemic immunization with cholera toxin.

Journal Article Vaccine · August 1994 We have used the potent mucosal immunogen cholera toxin (CT) to assess antigen-specific CD4+ T-cell responses, including Th1- and Th2-type cells in mucosa-associated tissues, e.g. Peyer's patches (PP), and systemic tissue, e.g. spleen (SP), for their regul ... Full text Link to item Cite

Mucosal immunity to infection with implications for vaccine development.

Journal Article Curr Opin Immunol · August 1994 The induction of effective mucosal immunity that also provides systemic immunity is a considerable challenge. Over the past two years, efforts to develop novel mucosal vaccine delivery systems to induce mucosal immunity against bacterial and viral diseases ... Full text Link to item Cite

The common mucosal immune system: from basic principles to enteric vaccines with relevance for the female reproductive tract.

Journal Article Reprod Fertil Dev · 1994 The realization that induction of immune responses at mucosal surfaces may prevent colonization, invasion or dissemination of pathogenic microorganisms has spurred intensive efforts to develop vaccines which elicit effective mucosal immunity. In this paper ... Full text Link to item Cite

Helper T cell subsets for immunoglobulin A responses: oral immunization with tetanus toxoid and cholera toxin as adjuvant selectively induces Th2 cells in mucosa associated tissues.

Journal Article J Exp Med · October 1, 1993 Antigen-specific B cell responses to mucosally delivered proteins are dependent upon CD4-positive T helper (Th) cells, and the frequency of Th1 and Th2 cell responses after oral immunization may determine the level and isotype of mucosal antibody responses ... Full text Link to item Cite

Cytokine expression in vivo during murine herpetic stromal keratitis. Effect of protective antibody therapy.

Journal Article J Immunol · July 1, 1993 HSV-1 topical infection on the murine cornea can induce herpetic stromal keratitis (HSK), a T cell-mediated inflammatory response that results in blindness. To begin to decipher the molecular interactions involved in this infection, extracts of infected co ... Link to item Cite

Anti-glycoprotein D monoclonal antibody protects against herpes simplex virus type 1-induced diseases in mice functionally depleted of selected T-cell subsets or asialo GM1+ cells.

Journal Article J Virol · November 1991 Passive transfer of a monoclonal antibody (MAb) specific for glycoprotein D (gD) is highly effective in preventing the development of herpes simplex virus type 1-induced stromal keratitis. In the present study, we investigated whether animals which had bee ... Full text Link to item Cite

Prevention of herpes keratitis by monoclonal antibodies specific for discontinuous and continuous epitopes on glycoprotein D.

Journal Article Invest Ophthalmol Vis Sci · September 1991 Seven monoclonal antibodies (mAb) specific for defined discontinuous and continuous epitopes on glycoprotein D of herpes simplex virus type 1 (HSV-1) were surveyed for their capacity to protect against virus-induced corneal disease in a murine ocular infec ... Link to item Cite

Effective antibody therapy in herpes simplex virus ocular infection. Characterization of recipient immune response.

Journal Article Intervirology · 1990 The immunotherapeutic potential of a monoclonal antibody specific for glycoprotein D of herpes simplex virus was evaluated in a murine ocular infection model. Passive transfer of antibody at microgram concentrations was able to promote resolution of cornea ... Full text Link to item Cite