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Journal articles on the topic 'Mucosal vaccine'
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1
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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Czerkinsky, Cecil, and Jan Holmgren. "Vaccines against enteric infections for the developing world." Philosophical Transactions of the Royal Society B: Biological Sciences 370, no. 1671 (June 19, 2015): 20150142. http://dx.doi.org/10.1098/rstb.2015.0142.
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Since the first licensure of the Sabin oral polio vaccine more than 50 years ago, only eight enteric vaccines have been licensed for four disease indications, and all are given orally. While mucosal vaccines offer programmatically attractive tools for facilitating vaccine deployment, their development remains hampered by several factors: — limited knowledge regarding the properties of the gut immune system during early life; — lack of mucosal adjuvants, limiting mucosal vaccine development to live-attenuated or killed whole virus and bacterial vaccines; — lack of correlates/surrogates of mucosal immune protection; and — limited knowledge of the factors contributing to oral vaccine underperformance in children from developing countries. There are now reasons to believe that the development of safe and effective mucosal adjuvants and of programmatically sound intervention strategies could enhance the efficacy of current and next-generation enteric vaccines, especially in lesser developed countries which are often co-endemic for enteric infections and malnutrition. These vaccines must be safe and affordable for the world's poorest, confer long-term protection and herd immunity, and must be able to contain epidemics.
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Lindholm, Catharina, Andrew Naylor, Eva-Liz Johansson, and Marianne Quiding-Järbrink. "Mucosal Vaccination Increases Endothelial Expression of Mucosal Addressin Cell Adhesion Molecule 1 in the Human Gastrointestinal Tract." Infection and Immunity 72, no. 2 (February 2004): 1004–9. http://dx.doi.org/10.1128/iai.72.2.1004-1009.2004.
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ABSTRACT Homing of leukocytes to various tissues is dependent on the interaction between homing receptors on leukocytes and their ligands, addressins, on endothelial cells. Mucosal immunization results in homing of antigen-specific lymphocytes back to the mucosa where they first encountered the antigen. However, it is unknown whether this homing of antigen-specific cells is mediated by an altered endothelial addressin expression after vaccination. Using different immunization routes with an oral cholera vaccine, we show that the endothelial expression of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) is increased in the gastric and upper small intestinal mucosae after immunization through various local routes in the upper gastrointestinal tract. In contrast, rectal immunization did not influence the levels of MAdCAM-1 in the gastric or duodenal mucosa. Furthermore, we show that MAdCAM-1 can be induced on human endothelial cells by tumor necrosis factor alpha (TNF-α) and gamma interferon. The vaccine component cholera toxin B subunit (CTB) increased MAdCAM-1 expression on endothelial cells in cultured human gastric explants, an effect that seemed to be mediated by TNF-α. In conclusion, MAdCAM-1 expression is increased in the upper gastrointestinal tract after local immunizations with a vaccine containing CTB. This strongly suggests the involvement of MAdCAM-1 in the preferential homing of mucosal lymphocytes to their original site of activation.
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Bernasconi, Valentina, Karin Norling, Marta Bally, Fredrik Höök, and Nils Y. Lycke. "Mucosal Vaccine Development Based on Liposome Technology." Journal of Immunology Research 2016 (2016): 1–16. http://dx.doi.org/10.1155/2016/5482087.
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Immune protection against infectious diseases is most effective if located at the portal of entry of the pathogen. Hence, there is an increasing demand for vaccine formulations that can induce strong protective immunity following oral, respiratory, or genital tract administration. At present, only few mucosal vaccines are found on the market, but recent technological advancements and a better understanding of the principles that govern priming of mucosal immune responses have contributed to a more optimistic view on the future of mucosal vaccines. Compared to live attenuated vaccines, subcomponent vaccines, most often protein-based, are considered safer, more stable, and less complicated to manufacture, but they require the addition of nontoxic and clinically safe adjuvants to be effective. In addition, another limiting factor is the large antigen dose that usually is required for mucosal vaccines. Therefore, the combination of mucosal adjuvants with the recent progress in nanoparticle technology provides an attractive solution to these problems. In particular, the liposome technology is ideal for combining protein antigen and adjuvant into an effective mucosal vaccine. Here, we describe and discuss recent progress in nanoparticle formulations using various types of liposomes that convey strong promise for the successful development of the next generation of mucosal vaccines.
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Shi, Wei, Jianzhong Liu, Yujun Huang, and Liang Qiao. "Papillomavirus Pseudovirus: a Novel Vaccine To Induce Mucosal and Systemic Cytotoxic T-Lymphocyte Responses." Journal of Virology 75, no. 21 (November 1, 2001): 10139–48. http://dx.doi.org/10.1128/jvi.75.21.10139-10148.2001.
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ABSTRACT Intestinal mucosa is a portal for many infectious pathogens. Systemic immunization, in general, does not induce a cytotoxic T-lymphocyte (CTL) response at the mucosal surface. Because papillomavirus (PV) naturally infects mucosa and skin, we determined whether PV pseudovirus, i.e., PV-like particles in which unrelated DNA plasmids are packaged, could generate specific mucosal immunity. We found that the pseudovirus that encoded the lymphocytic choriomeningitis virus gp33 epitope induced a stronger CTL response than a DNA vaccine (plasmid) encoding the same epitope given systemically. The virus-like particles that were used to make the pseudoviruses provided an adjuvant effect for induction of CTLs by the DNA vaccine. The PV pseudovirus pseudoinfected mucosal and systemic lymphoid tissues when administered orally. Oral immunization with the pseudovirus encoding human PV type 16 mutant E7 induced mucosal and systemic CTL responses. In comparison, a DNA vaccine encoding E7, when given orally, did not induce a CTL response in intestinal mucosal lymphoid tissue. Further, oral immunization with the human PV pseudovirus encoding E7 protected mice against mucosal challenge with an E7-expressing bovine PV pseudovirus. Thus, PV pseudovirus can be used as a novel vaccine to induce mucosal and systemic CTL responses.
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Bradley, Mark P., Lyn A. Hinds, and Peter H. Bird. "A bait-delivered immunocontraceptive vaccine for the European red fox (Vulpes vulpes) by the year 2002?" Reproduction, Fertility and Development 9, no. 1 (1997): 111. http://dx.doi.org/10.1071/r96066.
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An orally-delivered immunocontraceptive vaccine is being developed for the control of fox populations. A number of genes (PH-20, LDH-C4, ZP3) encoding gamete proteins have been cloned, produced in recombinant expression systems and used in fertility trials to test the efficacy of these antigens. As the immunocontraceptive vaccine will be delivered in a bait, there is a requirement for a greater understanding of the immune responses of the reproductive mucosa in canids, and the assessment of the best vaccine delivery system that will evoke a mucosal antibody response. Several vaccine delivery systems including microencapsulated antigens, and both vaccinia virus and bacterial vectors are being investigated. Oral administration of Salmonella typhimurium recombinants expressing different fox sperm antigens stimulates both systemic IgG responses to the antigen and a mucosal immune response within the female reproductive tract in the fox, indicating that salmonella may have potential with respect to the oral delivery of antigen. The enhancement of mucosal immune responses to orally-delivered vaccines is also being examined, research focussing on the possible use of fox-specific cytokines or the β-subunit of cholera toxin in forming part of the vaccine construct.
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Reece, Jeanette, and Stephen Kent. "The future of mucosal HIV vaccines." Microbiology Australia 32, no. 3 (2011): 118. http://dx.doi.org/10.1071/ma11118.
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Approximately 33 million people live with the human immunodeficiency virus (HIV) and 2.6 million new infections are acquired each yea1. The development of an effective HIV vaccine that induces robust mucosal immunity represents a major global public health challenge. Large human efficacy trials of simple antibody-based and cytotoxic T cell-based vaccines have failed to provide any protection. The recent RV144 HIV vaccine efficacy trial in Thailand using a prime-boost combination of vaccines, however, showed modest efficacy (31%, p=0.04 on the primary analysis). Although the efficacy was marginal, the study has provided considerable hope that a vaccine to prevent infection by HIV may be feasible.
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Jensen, Owen, Shubhanshi Trivedi, Kelin Li, Jeffrey Aubé, J. Scott Hale, Edward T. Ryan, and Daniel T. Leung. "Use of a MAIT Activating Ligand, 5-OP-RU, as a Mucosal Adjuvant in a Murine Model of Vibrio cholerae O1 Vaccination." Pathogens and Immunity 7, no. 1 (August 24, 2022): 122–44. http://dx.doi.org/10.20411/pai.v7i1.525.
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Background: Mucosal-associated invariant T (MAIT) cells are innate-like T cells enriched in the mucosa with capacity for B-cell help. We hypothesize that targeting MAIT cells, using a MAIT-activating ligand as an adjuvant, could improve mucosal vaccine responses to bacterial pathogens such as Vibrio cholerae. Methods: We utilized murine models of V. cholerae vaccination to test the adjuvant potential of the MAIT-activating ligand, 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU). We measured V. cholerae-specific antibody and antibody-secreting cell responses and used flow cytometry to examine MAIT-cell and B-cell phenotype, in blood, bronchoalveolar lavage fluid (BALF), and mucosal tissues, following intranasal vaccination with live V. cholerae O1 or a V. cholerae O1 polysaccharide conjugate vaccine. Results: We report significant expansion of MAIT cells in the lungs (P < 0.001) and BALF (P < 0.001) of 5-OP-RU treated mice, and higher mucosal (BALF, P = 0.045) but not systemic (serum, P = 0.21) V. cholerae O-specific-polysaccharide IgG responses in our conjugate vaccine model when adjuvanted with low-dose 5-OP-RU. In contrast, despite significant MAIT cell expansion, no significant differences in V. cholerae-specific humoral responses were found in our live V. cholerae vaccination model. Conclusions: Using a murine model, we demonstrate the potential, as well as the limitations, of targeting MAIT cells to improve antibody responses to mucosal cholera vaccines. Our study highlights the need for future research optimizing MAIT-cell targeting for improving mucosal vaccines.
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Venkatesan, Malabi M., Cassandra Ballou, Shoshana Barnoy, Monica McNeal, Jill El-Khorazaty, Robert Frenck, and Shahida Baqar. "Antibody in Lymphocyte Supernatant (ALS) responses after oral vaccination with live Shigella sonnei vaccine candidates WRSs2 and WRSs3 and correlation with serum antibodies, ASCs, fecal IgA and shedding." PLOS ONE 16, no. 11 (November 18, 2021): e0259361. http://dx.doi.org/10.1371/journal.pone.0259361.
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The levels of antigen-specific Antibodies in Lymphocyte Supernatant (ALS) using an ELISA are being used to evaluate mucosal immune responses as an alternate to measuring the number of Antibody Secreting Cells (ASCs) using an ELISpot assay. A recently completed trial of two novel S. sonnei live oral vaccine candidates WRSs2 and WRSs3 established that both candidates were safe, well tolerated and immunogenic in a vaccine dose-dependent manner. Previously, mucosal immune responses were measured by assaying IgA- and IgG-ASC in peripheral blood mononuclear cells (PBMCs). In this report, the magnitude of the S. sonnei antigen-specific IgA- and IgG-ALS responses was measured and correlated with previously described ASCs, serum antibodies, fecal IgA and vaccine shedding. Overall, the magnitude of S. sonnei anti-Invaplex50 ALS was higher than that of LPS or IpaB, and both vaccines demonstrated a more robust IgA-ALS response than IgG; however, compared to WRSs3, the magnitude and percentage of responders were higher among WRSs2 recipients for IgA- or IgG-ALS. All WRSs2 vaccinees at the two highest doses responded for LPS and Invaplex50-specific IgA-ALS and 63–100% for WRSs3 vaccinees responded. Regardless of the vaccine candidate, vaccine dose or detecting antigen, the kinetics of ALS responses were similar peaking on days 7 to 9 and returning to baseline by day 14. The ALS responses were vaccine-specific since no responses were detected among placebo recipients at any time. A strong correlation and agreement between responders/non-responders were noted between ALS and other mucosal (ASC and fecal IgA) and systemic (serum antibody) immune responses. These data indicate that the ALS assay can be a useful tool to evaluate mucosal responses to oral vaccination, an observation noted with trials of other bacterial diarrheal pathogens. Furthermore, this data will guide the list of immunological assays to be conducted for efficacy trials in different populations. It is hoped that an antigen-specific-ALS titer may be a key mucosal correlate of protection, a feature not currently available for any Shigella vaccines candidates. https://clinicaltrials.gov/show/NCT01336699.
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Kozlowski, Pamela A., and Anna Aldovini. "Mucosal Vaccine Approaches for Prevention of HIV and SIV Transmission." Current Immunology Reviews 15, no. 1 (April 12, 2019): 102–22. http://dx.doi.org/10.2174/1573395514666180605092054.
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Optimal protective immunity to HIV will likely require that plasma cells, memory B cells and memory T cells be stationed in mucosal tissues at portals of viral entry. Mucosal vaccine administration is more effective than parenteral vaccine delivery for this purpose. The challenge has been to achieve efficient vaccine uptake at mucosal surfaces, and to identify safe and effective adjuvants, especially for mucosally administered HIV envelope protein immunogens. Here, we discuss strategies used to deliver potential HIV vaccine candidates in the intestine, respiratory tract, and male and female genital tract of humans and nonhuman primates. We also review mucosal adjuvants, including Toll-like receptor agonists, which may adjuvant both mucosal humoral and cellular immune responses to HIV protein immunogens.
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Katsande, Paidamoyo M., Leira Fernández-Bastit, William T. Ferreira, Júlia Vergara-Alert, Mateusz Hess, Katie Lloyd-Jones, Huynh A. Hong, Joaquim Segales, and Simon M. Cutting. "Heterologous Systemic Prime–Intranasal Boosting Using a Spore SARS-CoV-2 Vaccine Confers Mucosal Immunity and Cross-Reactive Antibodies in Mice as well as Protection in Hamsters." Vaccines 10, no. 11 (November 10, 2022): 1900. http://dx.doi.org/10.3390/vaccines10111900.
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Background: Current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are administered systemically and typically result in poor immunogenicity at the mucosa. As a result, vaccination is unable to reduce viral shedding and transmission, ultimately failing to prevent infection. One possible solution is that of boosting a systemic vaccine via the nasal route resulting in mucosal immunity. Here, we have evaluated the potential of bacterial spores as an intranasal boost. Method: Spores engineered to express SARS-CoV-2 antigens were administered as an intranasal boost following a prime with either recombinant Spike protein or the Oxford AZD1222 vaccine. Results: In mice, intranasal boosting following a prime of either Spike or vaccine produced antigen-specific sIgA at the mucosa together with the increased production of Th1 and Th2 cytokines. In a hamster model of infection, the clinical and virological outcomes resulting from a SARS-CoV-2 challenge were ameliorated. Wuhan-specific sIgA were shown to cross-react with Omicron antigens, suggesting that this strategy might offer protection against SARS-CoV-2 variants of concern. Conclusions: Despite being a genetically modified organism, the spore vaccine platform is attractive since it offers biological containment, the rapid and cost-efficient production of vaccines together with heat stability. As such, employed in a heterologous systemic prime–mucosal boost regimen, spore vaccines might have utility for current and future emerging diseases.
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Jenkins, Paul G. "Mucosal vaccine delivery." Expert Opinion on Therapeutic Patents 9, no. 3 (March 1999): 255–62. http://dx.doi.org/10.1517/13543776.9.3.255.
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Coffey, Jacob William, Gaurav Das Gaiha, and Giovanni Traverso. "Oral Biologic Delivery: Advances Toward Oral Subunit, DNA, and mRNA Vaccines and the Potential for Mass Vaccination During Pandemics." Annual Review of Pharmacology and Toxicology 61, no. 1 (January 6, 2021): 517–40. http://dx.doi.org/10.1146/annurev-pharmtox-030320-092348.
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Oral vaccination enables pain-free and self-administrable vaccine delivery for rapid mass vaccination during pandemic outbreaks. Furthermore, it elicits systemic and mucosal immune responses. This protects against infection at mucosal surfaces, which may further enhance protection and minimize the spread of disease. The gastrointestinal (GI) tract presents a number of prospective mucosal inductive sites for vaccine targeting, including the oral cavity, stomach, and small intestine. However, currently available oral vaccines are effectively limited to live-attenuated and inactivated vaccines against enteric diseases. The GI tract poses a number of challenges,including degradative processes that digest biologics and mucosal barriers that limit their absorption. This review summarizes the approaches currently under development and future opportunities for oral vaccine delivery to established (intestinal) and relatively new (oral cavity, stomach) mucosal targets. Special consideration is given to recent advances in oral biologic delivery that offer promise as future platforms for the administration of oral vaccines.
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Li, Adrienne, James Moon, and Darrell Irvine. "Stabilized lipid nanocapsules eliciting potent mucosal immune response (P4509)." Journal of Immunology 190, no. 1_Supplement (May 1, 2013): 179.17. http://dx.doi.org/10.4049/jimmunol.190.supp.179.17.
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Abstract We investigated the use of a novel lipid nanocapsule, Interbilayer-Crosslinked Multilamellar Vesicles (ICMV), for mucosal vaccine delivery. ICMV co-encapsulated with MPLA and/or polyI:C as adjuvants, was used to vaccinate mice using model antigen and SIV-gag epitopes. When delivered via the lungs, we found that ~60-fold more antigen transported to the draining lymph nodes than equivalent subcutaneous vaccination, mediated by the vast number of antigen presenting cells in the lungs. Potent CD8 T-cell response was elicited by ICMV pulmonary vaccine and established a substantially greater memory population than a soluble vaccine, with 5.2-fold and 4.8-fold higher frequencies of antigen-specific cells in lungs and spleen, at 11 weeks post-priming. T-cells primed by ICMV pulmonary vaccination were also found to be strongly biased toward an effector memory phenotype, and a 5-7-fold higher number of effector memory cells were found in both the local and distal mucosa compared to soluble vaccines. Protection against a viral challenge was observed in animals given ICMV pulmonary vaccine while animals that received subcutaneous ICMV or pulmonary soluble vaccines showed steady weight loss that led to 100% mortality by day 5 post challenge. These particles can be prepared using aqueous solution processing techniques currently used for production of commercial liposomal products. They can also be freeze-dried for long term storage and have shown to retain immunogenicity after 1 month.
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Yagovkin, E. A., G. G. Onishchenko, A. Yu Popova, E. B. Ezhlova, A. A. Melnikova, M. Yu Soloviev, E. V. Kovalev, et al. "Condition and Prospects of Development of Vaccines for Specific Prevention of Enterovirus (Nonpolio) Infection." Epidemiology and Vaccine Prevention 15, no. 4 (August 20, 2016): 74–82. http://dx.doi.org/10.31631/2073-3046-2016-15-4-74-82.
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This review summarizes the material on the development of vaccines against (nonpolio) enterovirus infection in Russia and abroad. Described the developed vaccine types, their characteristics and the results of clinical and epidemiological trials, created in China inactivated vaccines. I’is considered the possibility of creating a mucosal vaccines and vaccinal prevention strategies.
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Vogel, Thorsten U., Matthew R. Reynolds, Deborah H. Fuller, Kathy Vielhuber, Tim Shipley, James T. Fuller, Kevin J. Kunstman, et al. "Multispecific Vaccine-Induced Mucosal Cytotoxic TLymphocytes Reduce Acute-Phase Viral Replication but Fail inLong-Term Control of Simian Immunodeficiency VirusSIVmac239." Journal of Virology 77, no. 24 (December 15, 2003): 13348–60. http://dx.doi.org/10.1128/jvi.77.24.13348-13360.2003.
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ABSTRACT Given the current difficulties generating vaccine-induced neutralizing antibodies to human immunodeficiency virus (HIV), the focus of the vaccine community has shifted toward creating cytotoxic-T-lymphocyte (CTL)-based vaccines. Recent reports of CTL-based vaccine trials in macaques challenged with simian/human immunodeficiency virus SHIV-89.6P have supported the notion that such vaccines can ameliorate the course of disease. However, almost all of these studies included Env as an immunogen and since SHIV-89.6P is sensitive to neutralizing antibodies it is difficult to determine the mechanism(s) of protection. Consequently, SHIV-89.6P challenge of macaques may be a poor model for determining vaccine efficacy in humans. To ascertain the effect of vaccine-induced multispecific mucosal CTL, in the absence of Env-specific antibody, on the control of an immunodeficiency virus challenge, we vaccinated Mamu-A*01+ macaques with constructs encoding a combination of CTL epitopes and full-length proteins (Tat, Rev, and Nef) by using a DNA prime/recombinant modified vaccinia virus Ankara (rMVA) boost regimen. The vaccination induced virus-specific CTL and CD4+ helper T lymphocytes with CTL frequencies as high as 20,000/million peripheral blood mononuclear cells. The final rMVA vaccination, delivered intravenously, engendered long-lived mucosal CTL. At 16 weeks after the final rMVA vaccination, the vaccinees and naive, Mamu-A*01+ controls were challenged intrarectally with SIVmac239. Massive early anamnestic cellular immune responses controlled acute-phase viral replication; however, the three vaccinees were unable to control virus replication in the chronic phase. The present study suggests that multispecific mucosal CTL, in the absence of neutralizing antibodies, can achieve a modicum of control over early viral replication but are unable to control chronic-phase viral replication after a high-dose mucosal challenge with a pathogenic simian immunodeficiency virus.
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Loehr, B. I., P. Willson, L. A. Babiuk, and S. van Drunen Littel-van den Hurk. "Gene Gun-Mediated DNA Immunization Primes Development of Mucosal Immunity against Bovine Herpesvirus 1 in Cattle." Journal of Virology 74, no. 13 (July 1, 2000): 6077–86. http://dx.doi.org/10.1128/jvi.74.13.6077-6086.2000.
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ABSTRACT Vaccination by a mucosal route is an excellent approach to the control of mucosally acquired infections. Several reports on rodents suggest that DNA vaccines can be used to achieve mucosal immunity when applied to mucosal tissues. However, with the exception of one study with pigs and another with horses, there is no information on mucosal DNA immunization of the natural host. In this study, the potential of inducing mucosal immunity in cattle by immunization with a DNA vaccine was demonstrated. Cattle were immunized with a plasmid encoding bovine herpesvirus 1 (BHV-1) glycoprotein B, which was delivered with a gene gun either intradermally or intravulvomucosally. Intravulvomucosal DNA immunization induced strong cellular immune responses and primed humoral immune responses. This was evident after BHV-1 challenge when high levels of both immunoglobulin G (IgG) and IgA were detected. Intradermal delivery resulted in lower levels of immunity than mucosal immunization. To determine whether the differences between the immune responses induced by intravulvomucosal and intradermal immunizations might be due to the efficacy of antigen presentation, the distributions of antigen and Langerhans cells in the skin and mucosa were compared. After intravulvomucosal delivery, antigen was expressed early and throughout the mucosa, but after intradermal administration, antigen expression occurred later and superficially in the skin. Furthermore, Langerhans cells were widely distributed in the mucosal epithelium but found primarily in the basal layers of the epidermis of the skin. Collectively, these observations may account for the stronger immune response induced by mucosal administration.
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Fujimoto, Kosuke, and Satoshi Uematsu. "Development of prime–boost-type next-generation mucosal vaccines." International Immunology 32, no. 9 (December 28, 2019): 597–603. http://dx.doi.org/10.1093/intimm/dxz085.
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Abstract Our bodies are constantly exposed to a wide variety of pathogenic micro-organisms through mucosal sites. Therefore, effective vaccines that can protect at the mucosa are vital; however, only a few clinically established mucosal vaccines are available. Although conventional injectable vaccines can induce antigen-specific serum immunoglobulin G (IgG) and prevent severe infection, it is difficult to efficiently inhibit the invasion of pathogens at mucosal surfaces because of the inadequate ability to induce antigen-specific IgA. Recently, we have developed a parenteral vaccine with emulsified curdlan and CpG oligodeoxynucleotides and reported its application. Unlike other conventional injectable vaccines, this immunization contributes to the induction of antigen-specific mucosal and systemic immune responses. Even if antigen-specific IgA at the mucosa disappears, this immunization can induce high-titer IgA after boosting with a small amount of antigen on the target mucosal surface. Indeed, vaccination with Streptococcus pneumoniae antigen effectively prevented lung infection induced by this bacterium. In addition, vaccination with Clostridium ramosum, which is a representative pathobiont associated with obesity and diabetes in humans, reduced obesity in mice colonized with this microorganism. This immunization approach might be an effective treatment for intestinal bacteria-mediated diseases that have been difficult to regulate so far, as well as common infectious diseases.
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Fuller, Deborah Heydenburg, Premeela A. Rajakumar, Lawrence A. Wilson, Anita M. Trichel, James T. Fuller, Tim Shipley, Mary S. Wu, et al. "Induction of Mucosal Protection against Primary, Heterologous Simian Immunodeficiency Virus by a DNA Vaccine." Journal of Virology 76, no. 7 (April 1, 2002): 3309–17. http://dx.doi.org/10.1128/jvi.76.7.3309-3317.2002.
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ABSTRACT An effective vaccine against human immunodeficiency virus (HIV) should protect against mucosal transmission of genetically divergent isolates. As a safe alternative to live attenuated vaccines, the immunogenicity and protective efficacy of a DNA vaccine containing simian immunodeficiency virus (SIV) strain 17E-Fr (SIV/17E-Fr) gag-pol-env was analyzed in rhesus macaques. Significant levels of cytotoxic T lymphocytes (CTL), but low to undetectable serum antibody responses, were observed following multiple immunizations. SIV-specific mucosal antibodies and CTL were also detected in rectal washes and gut-associated lymphoid tissues, respectively. Vaccinated and naive control monkeys were challenged intrarectally with SIV strain DeltaB670 (SIV/DeltaB670), a primary isolate whose env is 15% dissimilar to that of the vaccine strain. Four of seven vaccinees were protected from infection as determined by the inability to identify viral RNA or DNA sequences in the peripheral blood and the absence of anamnestic antibody responses postchallenge. This is the first report of mucosal protection against a primary pathogenic, heterologous isolate of SIV by using a commercially viable vaccine approach. These results support further development of a DNA vaccine for protection against HIV.
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Pan, Na, Bohui Liu, Xuemei Bao, Haochi Zhang, Shouxin Sheng, Yanchen Liang, Haiting Pan, and Xiao Wang. "Oral Delivery of Novel Recombinant Lactobacillus Elicit High Protection against Staphylococcus aureus Pulmonary and Skin Infections." Vaccines 9, no. 9 (September 3, 2021): 984. http://dx.doi.org/10.3390/vaccines9090984.
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Staphylococcus aureus is a leading cause of nosocomial and community-associated infection worldwide; however, there is no licensed vaccine available. S. aureus initiates infection via the mucosa; therefore, a mucosal vaccine is likely to be a promising approach against S. aureus infection. Lactobacilli, a non-pathogenic bacterium, has gained increasing interest as a mucosal delivery vehicle. Hence, we attempted to develop an oral S. aureus vaccine based on lactobacilli to cushion the stress of drug resistance and vaccine needs. In this study, we designed, constructed, and evaluated recombinant Lactobacillus strains synthesizing S. aureus nontoxic mutated α-hemolysins (HlaH35L). The results from animal clinical trials showed that recombinant Lactobacillus can persist for at least 72 h and can stably express heterologous protein in vivo. Recombinant L. plantarum WXD234 (pNZ8148-Hla) could induce robust mucosal immunity in the GALT, as evidenced by a significant increase in IgA and IL-17 production and the strong proliferation of T-lymphocytes derived from Peyer’s patches. WXD234 (pNZ8148-Hla) conferred up to 83% protection against S. aureus pulmonary infection and significantly reduced the abscess size in a S. aureus skin infection model. Of particular interest is the sharp reduction of the protective effect offered by WXD234 (pNZ8148-Hla) vaccination in γδ T cell-deficient or IL-17-deficient mice. In conclusion, for the first time, genetically engineered Lactobacillus WXD234 (pNZ8148-Hla) as an oral vaccine induced superior mucosal immunity, which was associated with high protection against pulmonary and skin infections caused by S. aureus. Taken together, our findings suggest the great potential for a delivery system based on lactobacilli and provide experimental data for the development of mucosal vaccines for S. aureus.
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Fletcher, Mark A. "Vaccine candidates in STD." International Journal of STD & AIDS 13, no. 1_suppl (December 2002): 38–41. http://dx.doi.org/10.1258/095646202762226155.
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Sexually transmitted diseases (STDs) are caused by organisms that infect the mucosal surfaces of the genitourinary tract. In spite of its public health importance, current STD vaccine research lags behind work against pathogens that target another mucosal region, the respiratory tract. In the latter case, live-attenuated viral vaccines, killed whole-cell bacterial vaccines, subunit/protein bacterial vaccines, and bacterial polysaccharide vaccines have been enormously successful. To move STD vaccine research forward, complex issues must be resolved. Those include selection of an appropriate antigen (e.g. scientific feasibility and intellectual property rights), the manufacture of the vaccine (e.g. delivery systems, formulation processes, and production steps), and the appropriate public health approach (e.g. medical indications and marketing aspects). Particular scientific problems have delayed STD vaccine development, like incomplete attenuation (human herpes simplex virus type 2), accentuated immunopathology (Chlamydia trachomatis), poor immunogenicity (Treponema pallidum), and broad antigenic heterogeneity (Neisseria gonorrhoeae). Nevertheless, efforts continue with the use of protein antigens: for example, the haemolysin toxoid of Haemophilus ducreyi; the major outer membrane protein(s) of N. gonorrhoeae and C. trachomatis; the glycoprotein D of human herpes simplex virus type 2; and the proteins E6 and E7 of human papilloma virus. It may be predicted that eventual STD vaccines (administered either for prophylaxis or for therapy) will use approaches that include (1) live-attenuated viruses, (2) subunit proteins or inactivated whole organisms given with mucosal adjuvants or with cellular immune response adjuvants, and (3) DNA plasmids expressing the vaccine antigen.
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Pal, Ranajit, David Venzon, Sampa Santra, Vaniambadi S. Kalyanaraman, David C. Montefiori, Lindsey Hocker, Lauren Hudacik, et al. "Systemic Immunization with an ALVAC-HIV-1/Protein Boost Vaccine Strategy Protects Rhesus Macaques from CD4+ T-Cell Loss and Reduces both Systemic and Mucosal Simian-Human Immunodeficiency Virus SHIVKU2 RNA Levels." Journal of Virology 80, no. 8 (April 15, 2006): 3732–42. http://dx.doi.org/10.1128/jvi.80.8.3732-3742.2006.
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ABSTRACT Transmission of human immunodeficiency virus type 1 (HIV-1) occurs primarily via the mucosal route, suggesting that HIV-1 vaccines may need to elicit mucosal immune responses. Here, we investigated the immunogenicity and relative efficacy of systemic immunization with two human ALVAC-HIV-1 recombinant vaccines expressing Gag, Pol, and gp120 (vCP250) or Gag, Pol, and gp160 (vCP1420) in a prime-boost protocol with their homologous vaccine native Env proteins. The relative efficacy was measured against a high-dose mucosal exposure to the pathogenic neutralization-resistant variant SHIVKU2 (simian-human immunodeficiency virus). Systemic immunization with both vaccine regimens decreased viral load levels not only in blood but unexpectedly also in mucosal sites and protected macaques from peripheral CD4+ T-cell loss. This protective effect was stronger when the gp120 antigen was included in the vaccine. Inclusion of recombinant Tat protein in the boosting phase along with the Env protein did not contribute further to the preservation of CD4+ T cells. Thus, systemic immunization with ALVAC-HIV-1 vaccine candidates elicits anti-HIV-1 immune responses able to contain virus replication also at mucosal sites in macaques.
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Wang, Shainn-Wei, Pamela A. Kozlowski, Gretchen Schmelz, Kelledy Manson, Michael S. Wyand, Rhona Glickman, David Montefiori, et al. "Effective Induction of Simian Immunodeficiency Virus-Specific Systemic and Mucosal Immune Responses in Primates by Vaccination with Proviral DNA Producing Intact but Noninfectious Virions." Journal of Virology 74, no. 22 (November 15, 2000): 10514–22. http://dx.doi.org/10.1128/jvi.74.22.10514-10522.2000.
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ABSTRACT We report a pilot evaluation of a DNA vaccine producing genetically inactivated simian immunodeficiency virus (SIV) particles in primates, with a focus on eliciting mucosal immunity. Our results demonstrate that DNA vaccines can be used to stimulate strong virus-specific mucosal immune responses in primates. The levels of immunoglobulin A (IgA) detected in rectal secretions of macaques that received the DNA vaccine intradermally and at the rectal mucosa were the most striking of all measured immune responses and were higher than usually achieved through natural infection. However, cytotoxic T lymphocyte responses were generally low and sporadically present in different animals. Upon rectal challenge with cloned SIVmac239, resistance to infection was observed, but some animals with high SIV-specific IgA levels in rectal secretions became infected. Our results suggest that high levels of IgA alone are not sufficient to prevent the establishment of chronic infection, although mucosal IgA responses may have a role in reducing the infectivity of the initial viral inoculum.
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Joag, Vineet, Jason Mitchell, Brian T. Fife, and David Masopust. "CD8 T cell immunosurveillance and elimination of HIV target cells in the female reproductive tract." Journal of Immunology 204, no. 1_Supplement (May 1, 2020): 157.3. http://dx.doi.org/10.4049/jimmunol.204.supp.157.3.
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Abstract HIV infection is thought to establish in a single founder CD4 T cell in the genital mucosa, however, an effective CD8 T cell-based vaccine must enable timely surveillance of all mucosal CD4 T cells within the first few days after HIV exposure. The HVTN 502 (STEP) vaccine trial employed a CD8 T cell based vaccine that while promising in animal studies, did not protect human vaccinees from mucosal HIV acquisition. We hypothesize that the quantity of mucosal HIV-specific CD8 T cells is a critical determinant of tissue immunosurveillance and was insufficient to adequately survey and eliminate HIV target cells in the STEP trial. To test our hypothesis, we applied intravital mucosal imaging to visualize how efficiently CD8 T cells survey CD4 T cells in the murine uterus. Based on CD8-CD4 T cell contact rates, a density of 4 (0.8%) HIV-specific mucosal CD8 T cells/mm2 would be required to survey all mucosal CD4 T cells within 2 days. However, vaccinees in the STEP trial had ELISPOT readings of ≥55 spot-forming units/106 blood leucocytes or approximately 0.09% mucosal HIV-specific CD8 T cells, which is 10 fold lower than the required density. Surveillance efficiency was directly correlated with the number of CD8 T cells and was independent of target cell numbers. Upon antigen recognition in the context of MHC-I on CD4 T cells, CD8 T cells formed kinapses with CD4 T cells in an LFA-1/ICAM-1 dependent manner, facilitating tethering and prolonged tracking. Direct killing of CD4 T cells by single or multiple CD8 T cells occurred by 3h after antigen presentation. We conclude that CD8 T cells are capable of rapid tissue surveillance and killing of CD4 T cell targets, and that sub-optimal numbers of HIV-specific CD8 T cells may have contributed to the failure of the STEP trial.
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Vilander and Dean. "Adjuvant Strategies for Lactic Acid Bacterial Mucosal Vaccines." Vaccines 7, no. 4 (October 16, 2019): 150. http://dx.doi.org/10.3390/vaccines7040150.
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Lactic acid bacteria (LAB) are Gram-positive, acid-tolerant bacteria that have long been used in food fermentation and are generally recognized as safe (GRAS). LAB are a part of a normal microbiome and act as probiotics, improving the gastrointestinal microbiome and health when consumed. An increasing body of research has shown the importance of the microbiome on both mucosal immune heath and immune response to pathogens and oral vaccines. Currently, there are few approved mucosal vaccines, and most are attenuated viruses or bacteria, which necessitates cold chain, carries the risk of reversion to virulence, and can have limited efficacy in individuals with poor mucosal health. On account of these limitations, new types of mucosal vaccine vectors are necessary. There has been increasing interest and success in developing recombinant LAB as next generation mucosal vaccine vectors due to their natural acid and bile resistance, stability at room temperature, endogenous activation of innate and adaptive immune responses, and the development of molecular techniques that allow for manipulation of their genomes. To enhance the immunogenicity of these LAB vaccines, numerous adjuvant strategies have been successfully employed. Here, we review these adjuvant strategies and their mechanisms of action which include: Toll-like receptor ligands, secretion of bacterial toxins, secretion of cytokines, direct delivery to antigen presenting cells, and enterocyte targeting. The ability to increase the immune response to LAB vaccines gives them the potential to be powerful mucosal vaccine vectors against mucosal pathogens.
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Wang, Maowei, Yan Yue, Chunsheng Dong, Xiaoyun Li, Wei Xu, and Sidong Xiong. "Mucosal Immunization with High-Mobility Group Box 1 in Chitosan Enhances DNA Vaccine-Induced Protection against Coxsackievirus B3-Induced Myocarditis." Clinical and Vaccine Immunology 20, no. 11 (September 11, 2013): 1743–51. http://dx.doi.org/10.1128/cvi.00466-13.
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ABSTRACTCoxsackievirus B3 (CVB3), a small single-stranded RNA virus, belongs to thePicornaviridaefamily. Its infection is the most common cause of myocarditis, with no vaccine available. Gastrointestinal mucosa is the major entry port for CVB3; therefore, the induction of local immunity in mucosal tissues may help control initial viral infections and alleviate subsequent myocardial injury. Here we evaluated the ability of high-mobility group box 1 (HMGB1) encapsulated in chitosan particles to enhance the mucosal immune responses induced by the CVB3-specific mucosal DNA vaccine chitosan-pVP1. Mice were intranasally coimmunized with 4 doses of chitosan-pHMGB1 and chitosan-pVP1 plasmids, at 2-week intervals, and were challenged with CVB3 4 weeks after the last immunization. Compared with chitosan-pVP1 immunization alone, coimmunization with chitosan-pHMGB1 significantly (P< 0.05) enhanced CVB3-specific fecal secretory IgA levels and promoted mucosal T cell immune responses. In accordance, reduced severity of myocarditis was observed in coimmunized mice, as evidenced by significantly (P< 0.05) reduced viral loads, decreased myocardial injury, and increased survival rates. Flow cytometric analysis indicated that HMGB1 enhanced dendritic cell (DC) recruitment to mesenteric lymph nodes and promoted DC maturation, which might partly account for its mucosal adjuvant effect. This strategy may represent a promising approach to candidate vaccines against CVB3-induced myocarditis.
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Cromwell, Mandy A., Ronald S. Veazey, John D. Altman, Keith G. Mansfield, Rhona Glickman, Todd M. Allen, David I. Watkins, Andrew A. Lackner, and R. Paul Johnson. "Induction of Mucosal Homing Virus-Specific CD8+ T Lymphocytes by Attenuated Simian Immunodeficiency Virus." Journal of Virology 74, no. 18 (September 15, 2000): 8762–66. http://dx.doi.org/10.1128/jvi.74.18.8762-8766.2000.
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ABSTRACT Induction of virus-specific T-cell responses in mucosal as well as systemic compartments of the immune system is likely to be a critical feature of an effective AIDS vaccine. We investigated whether virus-specific CD8+ lymphocytes induced in rhesus macaques by immunization with attenuated simian immunodeficiency virus (SIV), an approach that is highly effective in eliciting protection against mucosal challenge, express the mucosa-homing receptor α4β7 and traffic to the intestinal mucosa. SIV-specific CD8+ T cells expressing α4β7 were detected in peripheral blood and intestine of macaques infected with attenuated SIV. In contrast, virus-specific T cells in blood of animals immunized cutaneously by a combined DNA-modified vaccinia virus Ankara regimen did not express α4β7. These results demonstrate the selective induction of SIV-specific CD8+ T lymphocytes expressing α4β7 by a vaccine approach that replicates in mucosal tissue and suggest that induction of virus-specific lymphocytes that are able to home to mucosal sites may be an important characteristic of a successful AIDS vaccine.
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Cheng, Yanqing, Shaoyu Tu, Tong Chen, Jiahui Zou, Sheng Wang, Meijun Jiang, Shan Tian, Qingli Guo, Sizhu Suolang, and Hongbo Zhou. "Evaluation of the Mucosal Immunity Effect of Bovine Viral Diarrhea Virus Subunit Vaccine E2Fc and E2Ft." International Journal of Molecular Sciences 24, no. 4 (February 20, 2023): 4172. http://dx.doi.org/10.3390/ijms24044172.
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Classified as a class B infectious disease by the World Organization for Animal Health (OIE), bovine viral diarrhea/mucosal disease is an acute, highly contagious disease caused by the bovine viral diarrhea virus (BVDV). Sporadic endemics of BVDV often lead to huge economic losses to the dairy and beef industries. To shed light on the prevention and control of BVDV, we developed two novel subunit vaccines by expressing bovine viral diarrhea virus E2 fusion recombinant proteins (E2Fc and E2Ft) through suspended HEK293 cells. We also evaluated the immune effects of the vaccines. The results showed that both subunit vaccines induced an intense mucosal immune response in calves. Mechanistically, E2Fc bonded to the Fc γ receptor (FcγRI) on antigen-presenting cells (APCs) and promoted IgA secretion, leading to a stronger T-cell immune response (Th1 type). The neutralizing antibody titer stimulated by the mucosal-immunized E2Fc subunit vaccine reached 1:64, which was higher than that of the E2Ft subunit vaccine and that of the intramuscular inactivated vaccine. The two novel subunit vaccines for mucosal immunity developed in this study, E2Fc and E2Ft, can be further used as new strategies to control BVDV by enhancing cellular and humoral immunity.
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Harakuni, Tetsuya, Hideki Sugawa, Ai Komesu, Masayuki Tadano, and Takeshi Arakawa. "Heteropentameric Cholera Toxin B Subunit Chimeric Molecules Genetically Fused to a Vaccine Antigen Induce Systemic and Mucosal Immune Responses: a Potential New Strategy To Target Recombinant Vaccine Antigens to Mucosal Immune Systems." Infection and Immunity 73, no. 9 (September 2005): 5654–65. http://dx.doi.org/10.1128/iai.73.9.5654-5665.2005.
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ABSTRACT Noninvasive mucosal vaccines are attractive alternatives to parenteral vaccines. Although the conjugation of vaccine antigens with the B subunit of cholera toxin (CTB) is one of the most promising strategies for vaccine delivery to mucosal immune systems, the molecule cannot tolerate large-protein fusion, as it severely impairs pentamerization and loses affinity for GM1-ganglioside. Here we report a new strategy, in which steric hindrance between CTB-antigen fusion subunits is significantly reduced through the integration of unfused CTB “molecular buffers” into the pentamer unit, making them more efficiently self-assemble into biologically active pentamers. In addition, the chimeric protein took a compact configuration, becoming small enough to be secreted, and one-step affinity-purified proteins, when administered through a mucosal route, induced specific immune responses in mice. Since our results are not dependent on the use of a particular expression system or vaccine antigen, this strategy could be broadly applicable to bacterial enterotoxin-based vaccine design.
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Rhee, Joon Haeng, Shee Eun Lee, and Soo Young Kim. "Mucosal vaccine adjuvants update." Clinical and Experimental Vaccine Research 1, no. 1 (2012): 50. http://dx.doi.org/10.7774/cevr.2012.1.1.50.
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Tufet, Marta. "Rice-based mucosal vaccine." Nature Reviews Immunology 7, no. 8 (July 20, 2007): 578–79. http://dx.doi.org/10.1038/nri2135.
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Criscuolo, E., V. Caputo, R. A. Diotti, G. A. Sautto, G. A. Kirchenbaum, and N. Clementi. "Alternative Methods of Vaccine Delivery: An Overview of Edible and Intradermal Vaccines." Journal of Immunology Research 2019 (March 4, 2019): 1–13. http://dx.doi.org/10.1155/2019/8303648.
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Vaccines are recognized worldwide as one of the most important tools for combating infectious diseases. Despite the tremendous value conferred by currently available vaccines toward public health, the implementation of additional vaccine platforms is also of key importance. In fact, currently available vaccines possess shortcomings, such as inefficient triggering of a cell-mediated immune response and the lack of protective mucosal immunity. In this regard, recent work has been focused on vaccine delivery systems, as an alternative to injectable vaccines, to increase antigen stability and improve overall immunogenicity. In particular, novel strategies based on edible or intradermal vaccine formulations have been demonstrated to trigger both a systemic and mucosal immune response. These novel vaccination delivery systems offer several advantages over the injectable preparations including self-administration, reduced cost, stability, and elimination of a cold chain. In this review, the latest findings and accomplishments regarding edible and intradermal vaccines are described in the context of the system used for immunogen expression, their molecular features and capacity to induce a protective systemic and mucosal response.
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Hongying, Fan, Wu Xianbo, Yu Fang, Bai Yang, and Long Beiguo. "Oral Immunization with Recombinant Lactobacillus acidophilus Expressing the Adhesin Hp0410 of Helicobacter pylori Induces Mucosal and Systemic Immune Responses." Clinical and Vaccine Immunology 21, no. 2 (November 27, 2013): 126–32. http://dx.doi.org/10.1128/cvi.00434-13.
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ABSTRACTHelicobacter pyloriinfection is relatively common worldwide and is closely related to gastric mucosa-associated lymphoid tissue (MALT) lymphoma, chronic gastritis, and stomach ulcers. Therefore, a safe and effective method for preventingH. pyloriinfection is urgently needed. Given that developing an effective vaccine againstH. pyloriis one of the best alternatives,H. pyloriadhesin Hp0410 was expressed in the food-grade bacteriumLactobacillus acidophilus. The recombinant live bacterial vaccine was then used to orally vaccinate mice, and the immunoprotective effects of Hp0410-producing strains were investigated.H. pyloricolonization in the stomach of mice immunized with the recombinantL. acidophiluswas significantly reduced, in comparison with that in control groups. Furthermore, mucosal secretory IgA antibodies were elicited in the mucosal tissue of mice immunized with the recombinant bacteria, and specific anti-Hp0410 IgG responses were also detected in mouse serum. There was a significant increase in the level of protection against gastricHelicobacterinfection following a challenge withH. pyloriSydney strain 1 (SS1). Our results collectively indicate that adhesin Hp0410 is a promising candidate vaccine antigen, and recombinantL. acidophilusexpressing Hp0410 is likely to constitute an effective, low-cost, live bacterial vaccine againstH. pylori.
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Rakhra, Kavya, Wuhbet Abraham, Chensu Wang, Kelly D. Moynihan, Na Li, Nathan Donahue, Alexis D. Baldeon, and Darrell J. Irvine. "Exploiting albumin as a mucosal vaccine chaperone for robust generation of lung-resident memory T cells." Science Immunology 6, no. 57 (March 19, 2021): eabd8003. http://dx.doi.org/10.1126/sciimmunol.abd8003.
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Tissue-resident memory T cells (TRMs) can profoundly enhance mucosal immunity, but parameters governing TRM induction by vaccination remain poorly understood. Here, we describe an approach exploiting natural albumin transport across the airway epithelium to enhance mucosal TRM generation by vaccination. Pulmonary immunization with albumin-binding amphiphile conjugates of peptide antigens and CpG adjuvant (amph-vaccines) increased vaccine accumulation in the lung and mediastinal lymph nodes (MLNs). Amph-vaccines prolonged antigen presentation in MLNs over 2 weeks, leading to 25-fold increased lung-resident T cell responses over traditional immunization and enhanced protection from viral or tumor challenge. Mimicking such prolonged exposure through repeated administration of soluble vaccine revealed that persistence of both antigen and adjuvant was critical for optimal TRM induction, mediated through T cell priming in MLNs after prime, and directly in the lung tissue after boost. Thus, vaccine persistence strongly promotes TRM induction, and amph-conjugates may provide a practical approach to achieve such kinetics in mucosal vaccines.
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Baudner, B. C., O. Balland, M. M. Giuliani, P. Von Hoegen, R. Rappuoli, D. Betbeder, and G. Del Giudice. "Enhancement of Protective Efficacy following Intranasal Immunization with Vaccine Plus a Nontoxic LTK63 Mutant Delivered with Nanoparticles." Infection and Immunity 70, no. 9 (September 2002): 4785–90. http://dx.doi.org/10.1128/iai.70.9.4785-4790.2002.
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ABSTRACT Most vaccines are still given parenterally. Mucosal vaccination would offer different advantages over parenteral immunization, including blocking of the pathogens at the portal of entry. In this paper, nontoxic Escherichia coli heat-labile enterotoxin (LT) mutants and Supramolecular Biovector systems (SMBV) were evaluated in mice as mucosal adjuvants and delivery systems, respectively, for intranasal immunization with the conjugated group C meningococcal vaccine. The conjugated vaccine formulated together with the LT mutants and the SMBV induced very high titers of serum and mucosal antibodies specific for the group C meningococcal polysaccharide. This vaccination strategy also induced high titers of antibodies with bactericidal activity, which is known to correlate with efficacy. Importantly, the mucosal vaccination, but not the conventional parenteral vaccination, induced bactericidal antibodies at the mucosal level. These data strongly support the feasibility of development of intranasal vaccines with an enhanced protective efficacy against meningococci and possibly against other encapsulated bacteria.
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Mohd Asri, Nur Ain, Keh Min Xuan, Rafeah Suppian, Norazmi Mohd Nor, Maryam Azlan, and Frank Camacho. "Tuberculosis (TB) Mucosal Vaccines: Current Efforts and Future Approaches." Asian Journal of Medicine and Biomedicine 6, S1 (November 10, 2022): 190–91. http://dx.doi.org/10.37231/ajmb.2022.6.s1.582.
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It is now known that the existing vaccination, Bacille Calmette-Guérin (BCG), is unable to stop the global Tuberculosis (TB) epidemic, and TB continues to pose a serious threat to public health [1]. Mycobacterium tuberculosis (Mtb), the causing agent, enters the body by inhalation, causing TB predominantly a respiratory infection [1]. Therefore, there is solid evidence to support the idea that a mucosally administered TB vaccination would be more successful than one administered systemically. Our team in Universiti Sains Malaysia (USM) has been working with several organisations in conjunction with Malaysia’s National Vaccine Roadmap (PPVN) to address this problem as well as the government's goal to produce vaccines that are high-quality, efficient, and secure following the guidelines established by the National Pharmaceutical Regulatory Agency (NPRA).
Therefore, the development of TB mucosal vaccines over the past few years for worldwide as well as in USM is outlined in this presentation. It aims to discuss immunological and practical factors in the development of mucosal vaccines and emphasises some of the current and future approaches in USM.
As a result, it is acknowledged globally that matching the path of infection with the path of immunisation is an appealing strategy for the development of TB vaccines. Several approaches have been made in USM to produce a vaccine candidate that significantly induces mucosal immunity. The design of the study showed the manipulation of IgA, which is a hallmark of mucosal immunity, with multi-epitopes of TB to produce IgA: TB recombinant protein by using goat’s milk as a bioreactor. The concept of oral immunisation in-vivo also is an important approach in our effort to maximise the production of the immune system at the point of entry of bacteria.
In a conclusion, as a boost to a prior respiratory or systemic immunisation, the mucosal method might be more effective. In addition to systemic immunity obtained by injected vaccines, vaccines to induce pathogen-specific IgA are being developed to provide a first line of defence at these entry sites. Therefore, combining these concepts into developing new recombinant vaccine against TB would be a promising alternative.
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Nochi, Tomonori, Yoshikazu Yuki, Akiko Matsumura, Mio Mejima, Kazutaka Terahara, Dong-Young Kim, Satoshi Fukuyama, et al. "A novel M cell–specific carbohydrate-targeted mucosal vaccine effectively induces antigen-specific immune responses." Journal of Experimental Medicine 204, no. 12 (November 5, 2007): 2789–96. http://dx.doi.org/10.1084/jem.20070607.
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Mucosally ingested and inhaled antigens are taken up by membranous or microfold cells (M cells) in the follicle-associated epithelium of Peyer's patches or nasopharynx-associated lymphoid tissue. We established a novel M cell–specific monoclonal antibody (mAb NKM 16–2-4) as a carrier for M cell–targeted mucosal vaccine. mAb NKM 16–2-4 also reacted with the recently discovered villous M cells, but not with epithelial cells or goblet cells. Oral administration of tetanus toxoid (TT)– or botulinum toxoid (BT)–conjugated NKM 16–2-4, together with the mucosal adjuvant cholera toxin, induced high-level, antigen-specific serum immunoglobulin (Ig) G and mucosal IgA responses. In addition, an oral vaccine formulation of BT-conjugated NKM 16–2-4 induced protective immunity against lethal challenge with botulinum toxin. An epitope analysis of NKM 16–2-4 revealed specificity to an α(1,2)-fucose–containing carbohydrate moiety, and reactivity was enhanced under sialic acid–lacking conditions. This suggests that NKM 16–2-4 distinguishes α(1,2)-fucosylated M cells from goblet cells containing abundant sialic acids neighboring the α(1,2) fucose moiety and from non-α(1,2)-fucosylated epithelial cells. The use of NKM 16–2-4 to target vaccine antigens to the M cell–specific carbohydrate moiety is a new strategy for developing highly effective mucosal vaccines.
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Zhang, Q., R. Lakshman, R. Burkinshaw, S. Choo, J. Everard, S. Akhtar, and A. Finn. "Primary and Booster Mucosal Immune Responses to Meningococcal Group A and C Conjugate and Polysaccharide Vaccines Administered to University Students in the United Kingdom." Infection and Immunity 69, no. 7 (July 1, 2001): 4337–41. http://dx.doi.org/10.1128/iai.69.7.4337-4341.2001.
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ABSTRACT Meningococcal group A+C capsular polysaccharide (PS) conjugate vaccines may prime for serum immunoglobulin G (IgG) memory responses to meningococcal capsular PS. It is not known whether these vaccines induce immunological memory at the mucosal level, which may be important in reducing nasopharyngeal carriage. Mucosal immune responses to meningococcal conjugate and PS vaccines in young adults were investigated. Healthy university students were randomized to receive either a groups A+C meningococcal conjugate vaccine (MACconj,n = 100) or a group A+C meningococcal PS vaccine (MACPS, n = 95). One year after the primary immunization, both groups were randomized again to receive a MACconj or a MACPS booster vaccination. Saliva samples were collected before and 1 month after the primary and booster vaccinations. Anti-meningococcal A (MenA) and C (MenC) PS IgA and IgG antibody levels were measured by a standard enzyme-linked immunosorbent assay. After the primary vaccination, salivary MenA and MenC IgG and MenA IgA concentrations were significantly increased after immunization with both MACconj and MACPS vaccines, but the salivary Men C IgA level was increased only after MACPS vaccine (P < 0.01). IgA responses to both serogroups were greater for MACPS than MACconj vaccine (P < 0.05), whereas no significant differences were seen for IgG responses. MenA IgG titers were higher after the MACPS booster in MACconj-primed subjects than after the MACPS primary vaccination, suggesting the presence of IgG memory. Antibody responses to a dose of either MACPS or MACconj were not significantly reduced in those previously given MACPS compared to the primary responses to those vaccines. Meningococcal A+C conjugate and PS vaccines induce significant mucosal responses in young adults. MACconj priming may induce IgG memory at the mucosal level, which is likely to be a reflection of an anamnestic serum IgG response. No evidence of mucosal hyporesponsiveness was observed after MACPS priming in this study.
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Gary, Ebony N., and Michele A. Kutzler. "Defensive Driving: Directing HIV-1 Vaccine-Induced Humoral Immunity to the Mucosa with Chemokine Adjuvants." Journal of Immunology Research 2018 (December 13, 2018): 1–14. http://dx.doi.org/10.1155/2018/3734207.
Full textAbstract:
A myriad of pathogens gain access to the host via the mucosal route; thus, vaccinations that protect against mucosal pathogens are critical. Pathogens such as HIV, HSV, and influenza enter the host at mucosal sites such as the intestinal, urogenital, and respiratory tracts. All currently licensed vaccines mediate protection by inducing the production of antibodies which can limit pathogen replication at the site of infection. Unfortunately, parenteral vaccination rarely induces the production of an antigen-specific antibody at mucosal surfaces and thus relies on transudation of systemically generated antibody to mucosal surfaces to mediate protection. Mucosa-associated lymphoid tissues (MALTs) consist of a complex network of immune organs and tissues that orchestrate the interaction between the host, commensal microbes, and pathogens at these surfaces. This complexity necessitates strict control of the entry and exit of lymphocytes in the MALT. This control is mediated by chemoattractant chemokines or cytokines which recruit immune cells expressing the cognate receptors and adhesion molecules. Exploiting mucosal chemokine trafficking pathways to mobilize specific subsets of lymphocytes to mucosal tissues in the context of vaccination has improved immunogenicity and efficacy in preclinical models. This review describes the novel use of MALT chemokines as vaccine adjuvants. Specific attention will be placed upon the use of such adjuvants to enhance HIV-specific mucosal humoral immunity in the context of prophylactic vaccination.
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Yamasaki, Satoshi, Yoshiaki Miura, Julia Davydova, Selwyn M. Vickers, and Masato Yamamoto. "A Single Intraduodenal Administration of Human Adenovirus 40 Vaccine Effectively Prevents Anaphylactic Shock." Clinical and Vaccine Immunology 20, no. 10 (July 24, 2013): 1508–16. http://dx.doi.org/10.1128/cvi.00417-13.
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ABSTRACTVaccine administration into the intestine is known to induce mucosal tolerance most efficiently. Therefore, developing a delivery system that targets the intestinal mucosa is expected to improve the efficiency of immunosuppression. Human enteric adenovirus serotype 40 (Ad40)-based vectors have the advantage of targeting intestinal mucosa, making them prime candidates as mucosal vaccine carriers for immunosuppression. Here, after both oral and intraduodenal administrations, the vector distribution of replication-defective recombinant Ad40 vectors (rAd40) was significantly higher than that of a conventional Ad vector based on human adenovirus 5 (Ad5) in ilea containing Peyer's patches. Single intraduodenal administration of rAd40 induced antigen-specific mucosal immunoreaction mediated by intestinal mucosal and systemic immunity. In ovalbumin-induced allergy mouse models, this approach inhibited antigen-specific delayed-type hypersensitivity reactions, diarrhea occurrence, and systemic anaphylaxis. Thus, a single intraduodenal administration of rAd40 provides a potent method of inducing allergen-specific mucosal tolerance and a new allergen-specific immunotherapy for overcoming problems with current therapies against life-threatening allergic reactions, including anaphylaxis.
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Hellfritzsch and Scherließ. "Mucosal Vaccination via the Respiratory Tract." Pharmaceutics 11, no. 8 (August 1, 2019): 375. http://dx.doi.org/10.3390/pharmaceutics11080375.
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Vaccine delivery via mucosal surfaces is an interesting alternative to parenteral vaccine administration, as it avoids the use of a needle and syringe. Mucosal vaccine administration also targets the mucosal immune system, which is the largest lymphoid tissue in the human body. The mucosal immune response involves systemic, antigen-specific humoral and cellular immune response in addition to a local response which is characterised by a predominantly cytotoxic T cell response in combination with secreted IgA. This antibody facilitates pathogen recognition and deletion prior to entrance into the body. Hence, administration via the respiratory mucosa can be favoured for all pathogens which use the respiratory tract as entry to the body, such as influenza and for all diseases directly affecting the respiratory tract such as pneumonia. Additionally, the different mucosal tissues of the human body are interconnected via the so-called “common mucosal immune system”, which allows induction of an antigen-specific immune response in distant mucosal sites. Finally, mucosal administration is also interesting in the area of therapeutic vaccination, in which a predominant cellular immune response is required, as this can efficiently be induced by this route of delivery. The review gives an introduction to respiratory vaccination, formulation approaches and application strategies.