Relevant bibliographies by topics / Mucosal vaccine

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  1. Journal articles
  2. Dissertations / Theses
  3. Books
  4. Book chapters
  5. Conference papers
  6. Reports

Academic literature on the topic 'Mucosal vaccine'

Author: Grafiati
Published: 4 June 2021
Last updated: 14 March 2023

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Journal articles on the topic "Mucosal vaccine"

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Feng, Fengling, Ziyu Wen, Jiaoshan Chen, Yue Yuan, Congcong Wang, and Caijun Sun. "Strategies to Develop a Mucosa-Targeting Vaccine against Emerging Infectious Diseases." Viruses 14, no. 3 (March 3, 2022): 520. http://dx.doi.org/10.3390/v14030520.

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Numerous pathogenic microbes, including viruses, bacteria, and fungi, usually infect the host through the mucosal surfaces of the respiratory tract, gastrointestinal tract, and reproductive tract. The mucosa is well known to provide the first line of host defense against pathogen entry by physical, chemical, biological, and immunological barriers, and therefore, mucosa-targeting vaccination is emerging as a promising strategy for conferring superior protection. However, there are still many challenges to be solved to develop an effective mucosal vaccine, such as poor adhesion to the mucosal surface, insufficient uptake to break through the mucus, and the difficulty in avoiding strong degradation through the gastrointestinal tract. Recently, increasing efforts to overcome these issues have been made, and we herein summarize the latest findings on these strategies to develop mucosa-targeting vaccines, including a novel needle-free mucosa-targeting route, the development of mucosa-targeting vectors, the administration of mucosal adjuvants, encapsulating vaccines into nanoparticle formulations, and antigen design to conjugate with mucosa-targeting ligands. Our work will highlight the importance of further developing mucosal vaccine technology to combat the frequent outbreaks of infectious diseases.
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Harrell, Jaikin, Lisa A. Morici, and James B. McLachlan. "The use of outer membrane vesicles as novel, mucosal adjuvants against intracellular bactiera." Journal of Immunology 208, no. 1_Supplement (May 1, 2022): 181.09. http://dx.doi.org/10.4049/jimmunol.208.supp.181.09.

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Abstract Many pathogens first enter the body via mucosal surfaces where they can then invade and disseminate systemically to cause disease. Despite this, most vaccines are given parenterally and are unable to induce mucosal immunity. Immunizing directly at the mucosa could solve this problem, however delivering vaccines at these surfaces often doesn’t invoke robust immunity. One way to alleviate this is to use adjuvants that can evoke an immune response. Most adjuvants, like aluminum salts, are unable to induce mucosal immunity and so novel adjuvants must be employed. Outer membrane vesicles (OMVs) from Burkholderia pseudomallei are potent immune mediators and have been shown to have adjuvant capabilities. The goal of this study is to highlight the role of OMVs as a novel adjuvant that can be used in the next generation of mucosal vaccines. To test this, we created an OMV-adjuvanted inactivated whole-cell vaccine against two intracellular pathogens – Salmonella Typhimurium and Francisella holarctica LVS that could be delivered mucosally. An oral vaccine against S. Typhimurium adjuvanted with OMVs showed protection against lethal challenge in addition to evoking antigen specific CD4 T cells, B cells, and anti-Salmonella antibodies. These antibodies induced greater bacterial killing in macrophages. We are currently exploring an OMV-adjuvanted oropharyngeally delivered vaccine against F. holarctica LVS. Immunity against Francisella requires both CD4 and CD8 T cells and we are determining how an OMV-adjuvanted vaccine will influence these immune cell populations. This study represents a novel approach to mucosal vaccines using OMVs as adjuvants. Supported by NIH U01 AI124289 NIH BAA HHSN72201800045C
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Chen, Shing C., David H. Jones, Ellen F. Fynan, Graham H. Farrar, J. Christopher S. Clegg, Harry B. Greenberg, and John E. Herrmann. "Protective Immunity Induced by Oral Immunization with a Rotavirus DNA Vaccine Encapsulated in Microparticles." Journal of Virology 72, no. 7 (1998): 5757–61. http://dx.doi.org/10.1128/jvi.72.7.5757-5761.1998.

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DNA vaccines are usually given by intramuscular injection or by gene gun delivery of DNA-coated particles into the epidermis. Induction of mucosal immunity by targeting DNA vaccines to mucosal surfaces may offer advantages, and an oral vaccine could be effective for controlling infections of the gut mucosa. In a murine model, we obtained protective immune responses after oral immunization with a rotavirus VP6 DNA vaccine encapsulated in poly(lactide-coglycolide) (PLG) microparticles. One dose of vaccine given to BALB/c mice elicited both rotavirus-specific serum antibodies and intestinal immunoglobulin A (IgA). After challenge at 12 weeks postimmunization with homologous rotavirus, fecal rotavirus antigen was significantly reduced compared with controls. Earlier and higher fecal rotavirus-specific IgA responses were noted during the peak period of viral shedding, suggesting that protection was due to specific mucosal immune responses. The results that we obtained with PLG-encapsulated rotavirus VP6 DNA are the first to demonstrate protection against an infectious agent elicited after oral administration of a DNA vaccine.
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Yasui, Hisako. "Mucosal Immunity/Mucosal Vaccine." Nippon Shokuhin Kagaku Kogaku Kaishi 56, no. 3 (2009): 191. http://dx.doi.org/10.3136/nskkk.56.191.

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Brown, T. A. "Immunity at Mucosal Surfaces." Advances in Dental Research 10, no. 1 (April 1996): 62–65. http://dx.doi.org/10.1177/08959374960100011201.

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The mucosae form a barrier between our bodies and a hostile external environment. Diseases and extrinsic factors which impair mucosal function may lead to serious consequences. The mucosal immune system is the primary mediator of specific immunity at mucosal surfaces. As such, it is responsible for maintaining homeostasis and for defense against both overt and opportunistic pathogens. For this reason, it is also the target of many new vaccine strategies for the induction of mucosal immunity. This brief review will examine the mucosal immune system, its role in maintaining the integrity of the mucosa, and some of the strategies aimed at enhancing specific immunity.
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Shi, Ci, Yan Wei Sun, Guang Yu Rong, Yang Zhang, and Kai Zhao. "Optimization of Preparation and Characterization of the Plasmid DNA from Newcastle Disease Virus Encapsulated in Chitosan Nanoparticles." Advanced Materials Research 1042 (October 2014): 19–25. http://dx.doi.org/10.4028/www.scientific.net/amr.1042.19.

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Newcastle disease (ND) is a highly contagious and lethality disease of poultry caused by Newcastle disease virus (NDV). ND is universally controlled by conventional vaccines. DNA vaccine is superior than conventional vaccines, but it also has some limitations. Nanopartciles mucosa delivery system using biodegradable materials could avoid defects of DNA vaccine. This study established a model with NDV DNA vaccine pVAX1-optiF immobilized into chitosan by complex coacervation method. Preparation process, physical and chemical characteristics of the nanoparticles were evaluated. The results demonstrated that pFDNA-CS-NPs showed suitable size, morphous regulation and well-distributed with a mean diameter of 199.5nm, polydispersity index of 0.336, encapsulation efficiency of 98.59±0.03%, loading capacity of 36.12±0.19 % and a Zeta potential of+11.2mV. This study is successfully preparated of NDV DNA vaccine mucosal immunity delivery system into chitosan as gene vector and laid a foundation for the further development of mucosal vaccines and drugs encapsulated in chitosan nanoparticles.
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Igietseme, Joseph U., John L. Portis, and Linda L. Perry. "Inflammation and Clearance of Chlamydia trachomatis in Enteric and Nonenteric Mucosae." Infection and Immunity 69, no. 3 (March 1, 2001): 1832–40. http://dx.doi.org/10.1128/iai.69.3.1832-1840.2001.

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ABSTRACT Immunization(s) fostering the induction of genital mucosa-targeted immune effectors is the goal of vaccines against sexually transmitted diseases. However, it is uncertain whether vaccine administration should be based on the current assumptions about the common mucosal immune system. We investigated the relationship between mucosal sites of infection, infection-induced inflammation, and immune-mediated bacterial clearance in mice using the epitheliotropic pathogenChlamydia trachomatis. Chlamydial infection of the conjunctival, pulmonary, or genital mucosae stimulated significant changes in tissue architecture with dramatic up-regulation of the vascular addressin, VCAM, a vigorous mixed-cell inflammatory response with an influx of α4β1+ T cells, and clearance of bacteria within 30 days. Conversely, intestinal mucosa infection was physiologically inapparent, with no change in expression of the local MAdCAM addressin, no VCAM induction, no histologically detectable inflammation, and no tissue pathology. Microbial clearance was complete within 60 days in the small intestine but bacterial titers remained at high levels for at least 8 months in the large intestine. These findings are compatible with the notion that VCAM plays a functional role in recruiting cells to inflammatory foci, and its absence from the intestinal mucosa contributes to immunologic homeostasis at that site. Also, expression of type 1 T cell-mediated immunity to intracellular Chlamydia may exhibit tissue-specific variation, with the rate and possibly the mechanism(s) of clearance differing between enteric and nonenteric mucosae. The implications of these data for the common mucosal immune system and the delivery of vaccines against mucosal pathogens are discussed.
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Foss, Dennis L., and Michael P. Murtaugh. "Mechanisms of vaccine adjuvanticity at mucosal surfaces." Animal Health Research Reviews 1, no. 1 (June 2000): 3–24. http://dx.doi.org/10.1017/s1466252300000025.

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AbstractThe vast majority of pathogens invade via mucosal surfaces, including those of the intestine. Vaccination directly on these surfaces may induce local protective immunity and prevent infection and disease. Although vaccine delivery to the gut mucosa is fraught with obstacles, immunization can be enhanced using adjuvants with properties specific to intestinal immunity. In this review, we present three general mechanisms of vaccine adjuvant function as originally described by Freund, and we discuss these principles with respect to intestinal adjuvants in general and to the prototypical mucosal adjuvant, cholera toxin. The key property of intestinal adjuvants is to induce an immunogenic context for the presentation of the vaccine antigen. The success of oral vaccine adjuvants is determined by their ability to induce a controlled inflammatory response in the gut-associated lymphoid tissues, characterized by the expression of various costimulatory molecules and cytokines. An understanding of the specific molecular mechanisms of adjuvanticity in the gut will allow the rational development of safe and effective oral vaccines.
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Lü, F. X., and R. S. Jacobson. "Oral Mucosal Immunity and HIV/SIV Infection." Journal of Dental Research 86, no. 3 (March 2007): 216–26. http://dx.doi.org/10.1177/154405910708600305.

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Human Immunodeficiency Virus (HIV) transmission through genital and rectal mucosa has led to intensive study of mucosal immune responses to HIV and to the development of a vaccine administered locally. However, HIV transmission through the oral mucosa is a rare event. The oral mucosa represents a physical barrier and contains immunological elements to prevent the invasion of pathogenic organisms. This particular defense differs between micro-compartments represented by the salivary glands, oral mucosa, and palatine tonsils. Secretory immunity of the salivary glands, unique features of cellular structure in the oral mucosa and palatine tonsils, the high rate of oral blood flow, and innate factors in saliva may all contribute to the resistance to HIV/Simian Immunodeficiency Virus (SIV) oral mucosal infection. In the early stage of HIV infection, humoral and cellular immunity and innate immune functions in oral mucosa are maintained. However, these particular immune responses may all be impaired as a result of chronic HIV infection. A better understanding of oral mucosal immune mechanisms should lead to improved prevention of viral and bacterial infections, particularly in immunocompromised persons with Acquired Immune Deficiency Syndrome (AIDS), and to the development of a novel strategy for a mucosal AIDS vaccine, as well as vaccines to combat other oral diseases, such as dental caries and periodontal diseases.
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González Aznar, Elizabeth, Belkis Romeu, Miriam Lastre, Caridad Zayas, Maribel Cuello, Osmir Cabrera, Yolanda Valdez, Mildrey Fariñas, and Oliver Pérez. "Mucosal and systemic immune responses induced by a single time vaccination strategy in mice." Canadian Journal of Microbiology 61, no. 8 (August 2015): 531–38. http://dx.doi.org/10.1139/cjm-2015-0063.

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Vaccination is considered by the World Health Organization as the most cost-effective strategy for controlling infectious diseases. In spite of great successes with vaccines, many infectious diseases are still leading killers, because of the inadequate coverage of many vaccines. Several factors have been responsible: number of doses, high vaccine reactogenicity, vaccine costs, vaccination policy, among others. Contradictorily, few vaccines are of single dose and even less of mucosal administration. However, more common infections occur via mucosa, where secretory immunoglobulin A plays an essential role. As an alternative, we proposed a novel protocol of vaccination called Single Time Vaccination Strategy (SinTimVaS) by immunizing 2 priming doses at the same time: one by mucosal route and the other by parenteral route. Here, the mucosal and systemic responses induced by Finlay adjuvants (AF Proteoliposome 1 and AF Cochleate 1) implementing SinTimVaS in BALB/c mice were evaluated. One intranasal dose of AF Cochleate 1 and an intramuscular dose of AF Proteoliposome 1 adsorbed onto aluminum hydroxide, with bovine serum albumin or tetanus toxoid as model antigens, administrated at the same time, induced potent specific mucosal and systemic immune responses. Also, we demonstrated that SinTimVaS using other mucosal routes like oral and sublingual, in combination with the subcutaneous route elicits immune responses. SinTimVaS, as a new immunization strategy, could increase vaccination coverage and reduce time–cost vaccines campaigns, adding the benefits of immune response in mucosa.
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Dissertations / Theses on the topic "Mucosal vaccine"

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FORTUNA, DOS REMEDIOS CATARINA. "NANOPARTICLES FOR MUCOSAL VACCINE DELIVERY." Doctoral thesis, Università degli Studi di Milano, 2018. http://hdl.handle.net/2434/565631.

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Influenza is a contagious respiratory disease often disregarded due to the mild symptoms associated with it. The economic burden that flu cases impose on health care systems is substantial, not only due to influenza pandemics, but also to required hospitalizations and the need for yearly revisions of seasonal influenza vaccines. The need for a universal influenza vaccine was already recognized by the Global Vaccine Action Plan. Currently, injection-based vaccination is the most common method for influenza immunization. However, evidence has shown that mucosal immune responses, representing an important first line of defense at these sites, since most pathogens enter the body through mucosal tissues, are most efficiently induced by administration of vaccines onto mucosal surfaces than injected vaccines. From the different mucosal tissues, the gastrointestinal tract is an attractive route to be explored for vaccination; nonetheless, oral influenza vaccines are not available yet. The intestinal homeostasis is tightly controlled by several components of the intestinal barrier, such as the mucus layer, epithelial cells with different functions and an underlying immune system that surveys the gut. Between microorganisms that normally inhabit our gut, food antigens constantly present in our diet and potential pathogens, the intestinal barrier has the difficult task of integrating external and internal signals received by different cells in order to establish the correct response, immunity or tolerance, according to the antigen. Hence, oral vaccines will encounter these same intestinal barrier components and face the same obstacles as any other oral antigen or gut microorganism. The UniVacFlu consortium is currently working to develop a new mucosal universal vaccine against influenza, exploring different immunogens, immunization routes and delivery systems. This study was undertaken to understand the potential of the influenza vaccine candidate CTA1-3M2e-DD and polysaccharidic lipidated nanoparticles (NPL) when immunization occurs through the oral route. We found that, while CTA1-3M2e-DD revealed a poor ability to cross the intestinal epithelium and target intestinal antigen-presenting cells, NPL were found to readily overcome the intestinal barrier and were found associated with both CX3CR1+ macrophages and CD103+ dendritic cells. Two different routes of NPL uptake were identified: one depends on Goblet cell-associated passages that allow the transfer of high amounts of NPL from the lumen to the intestinal lamina propria; the second relies on the direct acquisition of NPL by CX3CR1+ macrophages in Peyer’s patches by extension of trans-epithelial dendrites. Moreover, NPL as an oral vaccine vector was able to deliver the loaded antigen in the intestinal lamina propria and enhanced antigen presentation to CD4+ T lymphocytes in different organs. Despite increasing the availability of antigen, NPL did not induce tolerance towards the formulated antigen and a Th1 immune response was found at the level of the Peyer’s patches. We also identified the contribution of the starvation period in the immune response induced by the NPL formulation in our model of oral immunization. The full potential of NPL as a vaccine vector is currently being further investigated to understand its immunomodulatory properties.
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Gebril, Ayman Mohamed. "Development of a mucosal vaccine delivery system." Thesis, University of Strathclyde, 2013. http://oleg.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=24878.

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Woodberry, Tonia. "Development of a mucosal HIV polytope vaccine /." [St. Lucia, Qld.], 2001. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe16255.pdf.

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Ye, Lilin. "FcRn mediated mucosal immunity and subunit vaccine delivery." College Park, Md.: University of Maryland, 2009. http://hdl.handle.net/1903/9815.

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Thesis (Ph. D.) -- University of Maryland, College Park, 2009.
Thesis research directed by: Virginia-Maryland Regional College of Veterinary Medicine. Maryland Campus. Title from t.p. of PDF. Includes bibliographical references. Published by UMI Dissertation Services, Ann Arbor, Mich. Also available in paper.
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Bumgardner, Sara Ashley. "Innate Immunogenicity of Lactobacillus as a Mucosal Vaccine Vector." Thesis, North Carolina State University, 2016. http://pqdtopen.proquest.com/#viewpdf?dispub=10110534.

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Mucosal surfaces act as functional barriers against the perpetual bombardment of foreign antigens and pathogens to the body. This barrier is maintained by homeostatic interactions between the microbiome and cells of the innate and adaptive immune system, interactions that mucosal vaccines can exploit to yield both mucosal and systemic amnestic responses to foreign antigen. The commensal lactic acid Lactobacillus spp. represent one constituent of this microbiome that has been utilized as both a homeostatic promoting probiotic and as a vaccine vector. The immune modulatory capacity of Lactobacillus spp. has been demonstrated in proof-of-principle studies utilizing lactobacilli-based vaccine vectors against several pathogens. Our laboratory has focused on the development of Lactobacillus gasseri and Lactobacillus acidophilus NCFM (NCFM) as mucosal vaccine vectors for human immunodeficiency virus-1 (HIV-1), a mucosal pathogen affecting more than 35 million people worldwide and for which no current licensed vaccine exists. As activation of innate immune receptors, including toll-like receptor (TLR), NOD-like receptor (NLR), and C-type lectin receptor (CLR), by lactobacilli have been shown to be species and strain specific, characterizing the innate receptors specific to our vectors is important for rationale vaccine design.

We first demonstrate that in addition to the previously characterized TLR2/6 activating capacity of lactobacilli, L. gasseri and NCFM activate intracellular NOD2 receptor. Co-culture of murine macrophages with L.gasseri, NCFM, or NCFM-derived mutants NCK2025 and NCK2031 elicited an M2b-like phenotype, a phenotype associated with TH2 skewing and immune regulatory function. For NCFM, this M2b phenotype was dependent on expression of lipoteichoic acid and S layer proteins, as demonstrated by the use of respective mutants, NCK2025 and NCK2031. Through the use of macrophage genetic knockouts, we identified TLR2, NOD2, and inflammasome associated caspase 1 as contributors to macrophage activation to varying degrees, with NOD2 cooperating with caspase 1 for inflammasome derived IL-1β in a pyroptosis-independent fashion. Finally, utilizing an NCFM-based mucosal vaccine with surface expression of HIV-1 Gag, we show that NOD2 signaling and the presence of an intact microbiome is required for HIV-specific IgG. We show that lactobacilli differentially utilize innate immune pathways and highlight NOD2 as a key mediator of macrophage function and antigen-specific humoral responses to a NCFM-based mucosal vaccine vector.

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Thomas, Linda D., and n/a. "Pseudomonas aeruginosa : development of a mucosal vaccine for respiratory infection." University of Canberra. Human & Biomedical Sciences, 2001. http://erl.canberra.edu.au./public/adt-AUC20061109.130804.

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Pseudomonas aeruginosa (P. aeruginosa) is a frequently isolated pathogen that causes septicaemia and chronic respiratory infection. It exhibits a higher mortality rate than other gram-negative bacteria and the need for effective immunotherapy is emphasised by the frequency of antibiotic resistance associated with this organism. Mucosal immunisation with a whole killed cell P. aeruginosa vaccine has previously demonstrated a significant immune response in both rodent studies and human trials. This study is a continuation of that research, with the major goal being the identification of a purified protein antigen that could form the basis of a mucosal vaccine against P. aeruginosa. Specifically, the aims of this study were the development of purification protocols for the isolation of previously untested protein antigens, assessment of the efficacy of these antigens to enhance bacterial clearance in an animal model of acute respiratory infection, determination of the immune parameters that are associated with the resolution of P. aeruginosa respiratory infection and finally, cloning of an identified antigen which demonstrated vaccine efficacy. Protocols were established to isolate proteins for use as antigens in immune response studies. The proteins purified in this study were Pa 13, Azurin, acyl carrier protein (ACP), Amidase, Aminopeptidase, KatA and Pa70. These proteins were used to immunise rats by intestinal intra-Peyer's patch (IPP) inoculation and intratracheal (IT) boost. The immunisation protocol employed was designed to target mucosal antigen-specific immune responses where the route of immunisation, Peyer's patch (PP) intestinal inoculation, is akin to the oral delivery of antigens to the gut-associated lymphoid tissue (96). Investigations of a previously uncharacterised antigen, Pa60, later identified this protein as the P. aeruginosa catalase, KatA. This study demonstrated enhanced bacterial clearance of both homologous and heterologous challenge following immunisation with KatA. The level of clearance demonstrated by KatA was promising when compared to that of killed whole cell immunisation. KatA was cloned and studies with the recombinant protein showed enhanced bacterial clearance commensurate with that of the native protein. Immunisations with other proteins identified four additional antigens which enhanced bacterial clearance; Pa13, Pa40, Pa45 and Pa70. Amino acid sequence analysis indicated that Pa13 may be a novel protein, whereas Pa40 was determined to be amidase and Pa45, aminopeptidase. Pa70 was not successfully sequenced. These proteins were effective in significantly enhancing bacterial clearance of homologous P. aeruginosa challenge. For KatA, Pa13 and Pa70, clearance was associated with a marked phagocytic cell recruitment. In contrast, amidase and aminopeptidase demonstrated clearance with a minimal cellular response. Proteins; azurin and ACP were non-protective, failing to clear a live P aeruginosa challenge. Analysis of the antigen-specific responses of these nonprotective proteins and comparison with those antigens which enhanced bacterial clearance were used to determine factors that may contribute to the resolution of an acute pulmonary infection. The study has demonstrated that mucosal immunisation using purified protein antigens can enhance the clearance of pulmonary infection with P. aeruginosa. It has also contributed to the understanding of immune responses to newfound antigens of P. aeruginosa and identified antigen-specific responses which confirm their potential as vaccine candidates.
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Brew, Robert. "Investigation of immune responses induced by a mucosal SIV DNA vaccine." Thesis, King's College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.272140.

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Thompson, Joseph Michael Johnston Robert E. "Venezuelan equine encephalitis virus replicon particles mucosal vaccine vectors and biological adjuvants /." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2007. http://dc.lib.unc.edu/u?/etd,1006.

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Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2007.
Title from electronic title page (viewed Dec. 18, 2007). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Microbiology and Immunology." Discipline: Microbiology and Immunology; Department/School: Medicine.
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McGuire, Carolann. "Mucosal vaccination using a crude antigen and a synthetic peptide in the Trichinella spiralis model." Thesis, University of Nottingham, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.285567.

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Mills, Jamie-Lee S. "Modelling natural immunity to streptococcal mucosal infections and novel approaches to vaccine delivery." Thesis, Griffith University, 2022. http://hdl.handle.net/10072/414917.

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Streptococcus pyogenes causes significant global morbidity and mortally through a range of pathologies. The most common sites of infection are the upper respiratory tract and the skin, resulting in pharyngitis and impetigo respectively. Non-invasive infections are usually self-limiting; however, they have the potential to progress to life threatening invasive diseases such as toxic-shock syndrome and necrotizing fasciitis with a high rate of mortality. Furthermore, S. pyogenes infections can give rise to auto-immune sequelae of ARF/RHD and ASPGN that result in approximately 500 000 deaths each year. Despite global efforts that span decades, no human vaccine is approved for use. The major hurdles in vaccine development are the broad serotypic and antigenic diversity of S. pyogenes, the risk for potential auto-immune disease due to the molecular mimicry of the S. pyogenes M-protein (a prime vaccine target) and human cardiac myosin, and the ability of S. pyogenes to infect different body sites that require different protective immune mechanisms. Previous research has shown that exposure to S. pyogenes can result in protective antibodies, though immunity is slow to develop and its role in preventing subsequent infections is poorly understood. In addition, there is a need to understand the mechanism of cross-compartment immunity to aid in guiding vaccine development to protect from multiple serotypes and also at various infection sites. To understand the mechanisms involved in site-specific and cross-compartment immunity, repeated mucosal exposures to S. pyogenes non-lethal infections in mice were performed to mimic endemic settings. Repeated homologous mucosal infections resulted in significant site-specific protection that endured for at least 9 weeks. Mice developed type-specific serum antibodies and antibody secreting cells (ASCs) that increased with increasing number of infections. These data indicate that the longevity of the antibody response is governed by the number of prior mucosal infections; however, no direct correlation with protection was established. Mucosal protection indicated a role for cell-mediated immunity. Repeated acute mucosal infections resulted in significant neutrophil recruitment to the local site of inflammation that correlated with protection. Cytokine analysis suggested a role for IL-17A in mucosal protection, particularly for enduring protection. To assess the importance of IL-17, IL-17 knockout (IL-17-/-) mice were given repeated homologous mucosal infections. Unlike wild type BALB/c mice, IL-17-/- mice failed to generate mucosal protection with repeated exposures. Furthermore, IL-17-/- mice had significantly reduced M-protein type-specific salivary IgG, IgG and IgA-secreting cells in bone marrow, and neutrophil influx to the lung, correlating with lack of protection. Mice required only one prior mucosal infection to develop significant and long-lasting protection against a homologous mucosal challenge. However, when cross-compartment protection at the skin was assessed, mice required a minimum of four repeated mucosal infections to generate significant protection. These data suggest that developing a protective immune response by repeated exposures is unlikely in a real-world setting. The literature indicates that multiple different S. pyogenes types move through communities, and people rarely encounter the same strain again within a short period of time. Realising these constraints in developing naturally acquired immunity to S. pyogenes, the next question was then asked: ‘could vaccine mediated immunity be boosted and broadened via natural exposures to S. pyogenes?’ Vaccine candidates based on the conserved C-terminal region of S. pyogenes M-protein (p145) have made considerable progress. The C-terminal region of the M protein is conserved across the majority of S. pyogenes strains, therefore forgoing the issue of serotype diversity. Two vaccine epitopes at the forefront of development, J8 and p*17, when conjugated to the carrier protein, diphtheria toxoid (DT), create J8-DT and p*17-DT. p*17-DT delivered intramuscularly with the adjuvant, alum, (p*17-DT/Alum) has shown promising immunogenicity and protection against several S. pyogenes isolates; however, it does not protect mice against intranasal challenge with a hypervirulent covR/S mutant strain. To test the hypothesis that infection will boost vaccine-mediated immunity, mice received two vaccinations with p*17-DT/Alum, followed by repeated mucosal infections every three weeks with heterologous isolates. Mice that received vaccinations followed by sequential infections showed increasing protection against NALT (nasal associated lymphoid tissue) bacterial load with each subsequent infection when compared to naïve mice. Bacterial load in the NALT was significantly reduced in these mice following a covR/S mutant challenge. Antigen-specific ASCs were assessed as a determinant of humoral immunity. Although no increase in serum antibody levels or antibody avidity were observed between mice that received vaccination alone or when followed by repeated infections, the mice that received vaccination and sequential infections had significantly increased IgG secreting cells in the spleen. The ASCs, in combination with lung specific CD4+ T-cell responses may be contributing to increased protection seen in mice that were boosted with repeated heterologous infections. Although promising, the results were scattered, which may be attributed to the differences in sequence homology of p145 as well as characteristics of different isolates. These data suggest that vaccine-mediated immunity has the potential to be boosted with repeated exposures to S. pyogenes. However, it was demonstrated that there is room for improvement in vaccination strategy and alternative approaches should be explored. Therefore, the next aim was to assess if new delivery methods could be used to increase vaccine-mediated immunogenicity and protection. Different methods of vaccine delivery can invoke varied immune responses. Skin-based immunisation routes have gained attention due to targeting of the epidermis and dermis layers rich in immune cells. Several advantages are associated with cutaneous routes, particularly when using high density/micro array patches (MAPs and HD-MAPs). These include dose sparing, enhanced thermostability, ease of administration, reduced generation of sharp-waste and risk of needle-stick injuries, good tolerability and enhanced acceptability in patients. HD-MAPs, developed by Vaxxas Pty Ltd, are at an advanced stage of development and have shown promising clinical trials results. The aim of his final study was to determine if the M-protein-based vaccine candidate J8-DT would have comparable immunogenicity and protection if delivered on the adjuvant free HD-MAP in comparison to intramuscular delivery. The effect of dose sparing and the number of vaccinations on the antibody response profile of vaccinated mice were assessed. A reduction in the number of vaccinations (from three to two) with J8-DT/HD-MAP induced comparable antibody responses to three vaccinations with intramuscular J8-DT/Alum. J8-DT/HD-MAP vaccination led to a significant reduction in the number of S. pyogenes colony forming units in skin (92.9%) and blood (100%) compared to intramuscular vaccination with unadjuvanted J8-DT when assessed following skin challenge. J8-DT/HD-MAP induced a shift in the antibody isotype profile, with a bias towards Th1-related isotypes, compared to J8-DT/Alum (Th2 bias). Based on the results of this study, the use of J8-DT/HD-MAP should be considered in future clinical development and control programs against S. pyogenes. The studies in this thesis demonstrate the constraints in developing naturally acquired immunity and highlight the importance for developing an effective vaccine against S. pyogenes.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
Institute for Glycomics
Science, Environment, Engineering and Technology
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Books on the topic "Mucosal vaccine"

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Kozlowski, Pamela A. Mucosal Vaccines: Modern Concepts, Strategies, and Challenges. Berlin, Heidelberg: Springer Berlin Heidelberg, 2012.

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1941-, Paterson Yvonne, ed. Intracellular bacterial vaccine vectors: Immunology, cell biology, and genetics. New York: Wiley-Liss, 1999.

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Kozlowski, Pamela A., ed. Mucosal Vaccines. Berlin, Heidelberg: Springer Berlin Heidelberg, 2012. http://dx.doi.org/10.1007/978-3-642-23693-8.

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H, Kiyono, Ogra Pearay L, and McGhee Jerry R, eds. Mucosal vaccines. San Diego: Academic Press, 1996.

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Kraehenbuhl, Jean-Pierre, and Marian R. Neutra, eds. Defense of Mucosal Surfaces: Pathogenesis, Immunity and Vaccines. Berlin, Heidelberg: Springer Berlin Heidelberg, 1999. http://dx.doi.org/10.1007/978-3-642-59951-4.

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-P, Kraehenbuhl J., and Neutra M. R, eds. Defense of mucosal surfaces: Pathogenesis, immunity and vaccines. Berlin: Springer, 1999.

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Kozlowski, Pamela A. Mucosal Vaccines: Modern Concepts, Strategies, and Challenges. Springer, 2014.

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Gram-Positive Bacteria: Vaccine Vehicles for Mucosal Immunization. Springer, 1997.

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Gram-positive bacteria: Vaccine vehicles for mucosal immunization. Berlin: Springer, 1997.

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Wells, Jeremy M., and Gianni Pozzi. Gram-Positive Bacteria: Vaccine Vehicles for Mucosal Immunization. Springer London, Limited, 2013.

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Book chapters on the topic "Mucosal vaccine"

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McI.Mowat, Allan, Kevin J. Maloy, Rosemary E. Smith, and Anne M. Donachie. "Iscoms as Mucosal Vaccine Vectors." In Vaccine Design, 147–53. Boston, MA: Springer US, 1997. http://dx.doi.org/10.1007/978-1-4899-0062-3_14.

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Mannino, Raphael J., and Susan Gould-Fogerite. "Lipid Matrix-Based Vaccines for Mucosal and Systemic Immunization." In Vaccine Design, 363–87. Boston, MA: Springer US, 1995. http://dx.doi.org/10.1007/978-1-4615-1823-5_15.

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Payne, Lendon G., Sharon A. Jenkins, Alexander Andrianov, and Bryan E. Roberts. "Water-Soluble Phosphazene Polymers for Parenteral and Mucosal Vaccine Delivery." In Vaccine Design, 473–93. Boston, MA: Springer US, 1995. http://dx.doi.org/10.1007/978-1-4615-1823-5_20.

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Ghiara, Paolo. "Mucosal Vaccines: Perspectives on the Development of Anti-H.pylori Vaccines." In Vaccine Design, 59–66. Boston, MA: Springer US, 1997. http://dx.doi.org/10.1007/978-1-4899-0062-3_7.

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Tsai, Catherine, Jacelyn M. S. Loh, and Thomas Proft. "PilVax: A Novel Platform for the Development of Mucosal Vaccines." In Vaccine Design, 399–410. New York, NY: Springer US, 2021. http://dx.doi.org/10.1007/978-1-0716-1892-9_20.

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Irache, Juan M., Ana I. Camacho, and Carlos Gamazo. "Vaccine Delivery Systems for Veterinary Immunization." In Mucosal Delivery of Biopharmaceuticals, 379–406. Boston, MA: Springer US, 2014. http://dx.doi.org/10.1007/978-1-4614-9524-6_17.

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Zhang, Jingtuo, and Amish Patel. "Chapter 11. Development Considerations for Final Dosage Forms: Mucosal Bacterial Vaccines." In Vaccine Development, 237–61. Cambridge: Royal Society of Chemistry, 2022. http://dx.doi.org/10.1039/9781839162572-00237.

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Yamamoto, M., D. W. Pascual, and H. Kiyono. "M Cell-Targeted Mucosal Vaccine Strategies." In Current Topics in Microbiology and Immunology, 39–52. Berlin, Heidelberg: Springer Berlin Heidelberg, 2011. http://dx.doi.org/10.1007/82_2011_134.

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Richards, Angelene F., Fernando J. Torres-Velez, and Nicholas J. Mantis. "Salmonella Uptake into Gut-Associated Lymphoid Tissues: Implications for Targeted Mucosal and Delivery." In Vaccine Design, 305–24. New York, NY: Springer US, 2021. http://dx.doi.org/10.1007/978-1-0716-1884-4_15.

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Jennings, R., D. Ní Challanáin, H. O. Ghazi, and C. S. McLean. "Vaccines and Vaccine Delivery Systems: Experience with HSV, Influenza and Mucosal Routes of Immunisation." In Vaccine Design, 119–27. Boston, MA: Springer US, 1997. http://dx.doi.org/10.1007/978-1-4899-0062-3_12.

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Conference papers on the topic "Mucosal vaccine"

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Zhu, Richard, and Sujata Bhatia. "Optimizing COVID-19 Vaccine Diffusion in Respiratory Mucosa through Stokes-Einstein Modeling." In 2022 Design of Medical Devices Conference. American Society of Mechanical Engineers, 2022. http://dx.doi.org/10.1115/dmd2022-1065.

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Abstract SARS-COV-2 vaccines, all of which are currently intramuscular shots, have the ability to prevent serious injury. However, the absence of sufficient mucosal immunity is a major concern. To counteract this deficiency that has led to continued transmission from vaccinated individuals and breakthrough cases, reformulating vaccines to be inhalable presents a logical administration route. Predecessor research has reported the inhalable route to be viable as aerosolized vaccine nanoparticles, AAV phage nanoparticles, and PIV-5 viruses were recently identified to elicit immune responses. In this study, the diffusion of vaccine nanoparticles across the mucosa is characterized and modeled, with respect to their observed behavior from previous studies in relation to the Stokes-Einstein equation, to predict the most efficient model of an inhalable COVID-19 vaccine. The Stokes-Einstein equation has been used in several studies to predict diffusion coefficients. These predictions may be modified to fit the specifications of mucosal interactions. It was determined that mucosal interactions play a significant role in vaccine nanoparticle diffusion, as demonstrated by the viral vector and virus-like nanoparticle diffusion, and can be characterized by an equivalent hydrodynamic radius. Moreover, as a counter to mucosal interactions, PEGylation was found to drastically decrease the viscous slowing of the mucus medium.
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Krishnakumar, D., and K. S. Jaganathan. "Development of nasal HPV vaccine formulations." In 16th Annual International Conference RGCON. Thieme Medical and Scientific Publishers Private Ltd., 2016. http://dx.doi.org/10.1055/s-0039-1685403.

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Cervical cancer is the second most cancer in women worldwide with over 500000 new cases and 275000 deaths being registered every year. With nearly 73000 women dying every year, India now tops the world in cervical cancer deaths. India represents 26.4% of all women dying of cervical cancer globally. Cervical cancer estimated to be responsible for about 5% of human cancers worldwide. Currently available vaccines may not provide complete protection against all HPV types as the protection is primarily type specific. Furthermore, the available vaccines are delivered via intramuscular route and require three doses and require cold chain supply which increases the cost of vaccine. Therefore a single dose vaccine delivered via non-invasive route (nasal) that protects against multiple HPV types would be a cost effective and better alternative to the currently available HPV vaccines. The main objective of this study was to prepare HPV antigen loaded poly (lactic-co-glycolic acid) (PLGA) and Tri Methyl Chitosan (TMC) coated PLGA microparticles and compare their efficacy as nasal vaccine. The developed formulations were characterized for size, zeta potential, entrapment efficiency, mucin adsorption ability, in vitro and in vivo studies. PLGA microparticles demonstrated negative zeta potential whereas PLGA-TMC microparticles showed higher positive zeta potential. The protein loading efficiency was found as above 80%. Results indicated that PLGA-TMC microparticles demonstrated substantially higher mucin adsorption when compared to PLGA microparticles. HPV antigen encapsulated in PLGA-TMC particles elicited a significantly higher secretory (IgA) immune response compared to that encapsulated in PLGA particles. Present study demonstrates that PLGA-TMC microparticles with specific size range can be a better carrier adjuvant for nasal subunit vaccines. Surface modified PLGA microparticles proved great potential as a nasal delivery system for HPV infections where systemic and mucosal responses are necessary particularly in conditions after viral pathogens invade the host through the mucosal surface.
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Sandoval, Federico, Mevyn Nizard, Magali Terme, Cecile Badoual, Michel-Francis Bureau, Olivier Clement, Elie Marcheteau, et al. "Abstract 2830: Mucosal imprinting of vaccine induced-CD8+T cells is crucial to inhibit mucosal tumors." In Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-2830.

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Liu, S., K. Y. Chan, Y. Wei, and R. W. Chan. "mRNA vaccine boosts the SARS-CoV-2 specific mucosal antibody in recipients of inactivated and mRNA vaccines." In ERS International Congress 2022 abstracts. European Respiratory Society, 2022. http://dx.doi.org/10.1183/13993003.congress-2022.4469.

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Ozawa, Y., T. Suda, T. Nagata, D. Hashimoto, Y. Nakamura, N. Enomoto, N. Inui, Y. Koide, H. Nakamura, and K. Chida. "Mucosal CTL Epitope-Loaded Dendritic Cell Vaccine Confers Protection Against Intracellular Pathogens." In American Thoracic Society 2009 International Conference, May 15-20, 2009 • San Diego, California. American Thoracic Society, 2009. http://dx.doi.org/10.1164/ajrccm-conference.2009.179.1_meetingabstracts.a4291.

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Sevilla Ortega, A. C., A. Angelina Querencias, B. Marcos Ramiro, M. Pérez Diego, L. Conejero Hall, J. L. Subiza, and O. Palomares Gracia. "The polybacterial mucosal vaccine MV130 impairs airway inflammation in a HDM-induced eosinophilic asthma model." In ERS International Congress 2022 abstracts. European Respiratory Society, 2022. http://dx.doi.org/10.1183/13993003.congress-2022.3751.

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Bezerra, Izabella, Júlia Azevedo, and Bartira Bergmann. "Dietary retinol role and retinoic acid adjuvant effect in mucosal LaAg vaccine efficacy against Leishmania amazonensis infection." In III Seminário Anual Científico e Tecnológico de Bio-Manguinhos. Instituto de Tecnologia em Imunobiológicos, 2016. http://dx.doi.org/10.35259/isi.sact.2016_27344.

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Xiaoping Lv and Shimin Zheng. "Changes of the number of T lymphocytes in local mucosal tissues of probiotics chicks vaccinated with ND vaccine." In 2011 International Conference on Remote Sensing, Environment and Transportation Engineering (RSETE). IEEE, 2011. http://dx.doi.org/10.1109/rsete.2011.5965887.

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KRAEHENBUHL, JEAN-PIERRE. "DEVELOPMENT OF PLANT VACCINES: THE POINT OF VIEW OF THE MUCOSAL IMMUNOLOGIST." In International Seminar on Nuclear War and Planetary Emergencies 25th Session. Singapore: World Scientific Publishing Co. Pte. Ltd., 2001. http://dx.doi.org/10.1142/9789812797001_0013.

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Reports on the topic "Mucosal vaccine"

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Eldridge, John H., Terrence E. Greenway, Jay K. Staas, and Richard M. Gilley. Biodegradable Vaccine Microcapsules for Systemic and Mucosal Immunization against RVF and VEE Viruses. Fort Belvoir, VA: Defense Technical Information Center, March 1992. http://dx.doi.org/10.21236/adb164489.

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