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Vaccines
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Bacterial Vaccine: Mucosal Immunity and Implications
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Bacterial Vaccine: Mucosal Immunity and Implications

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Vaccines against Tropical and other Infectious Diseases".

Deadline for manuscript submissions: closed (30 September 2024) | Viewed by 14757

Special Issue Editors

Dr. Amit K. Singh

E-Mail Website
Guest Editor
Department of Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA
Interests: vaccine development; host–pathogen interaction; lung infectious disease; cell signaling
Dr. Raj Kumar

E-Mail Website
Guest Editor
Department of Physiology, The University of Tennessee Health Science Center, Memphis, TN 38163, USA
Interests: vascular pathology; cellular signaling; cell differentiation; angiogenesis; vascular biology and obesity

Special Issue Information

Dear Colleagues,

The aerodigestive and urogenital tracts, eye conjunctiva, inner ear, and the ducts of all exocrine glands are endowed with a powerful mucous layer; covering that by mechanical and chemical cleansing mechanisms degrades and repels most of the foreign matter. In addition, the mucous layer also protects these surfaces against potential insults from the environment by the recruitment of a large and highly specialized innate and adaptive mucosal immune system. Therefore, mucosal surfaces act as an interface and protective layer between the external atmosphere and host immune systems. In addition, alteration of the mucosal surface environment and/or mucosal immunity around the nasopharyngeal, gastrointestinal, oral, ocular, and genitourinary systems has been shown to compromise the continuous clearance of foreign particles, including antigens, allergens, and/or pathogens, and this condition poses a health risk to the host. Hence, the mucosal immune responses are considered the first line of protection against such invading pathogens. In this regard, mucosal vaccines can offer a robust protective immune response at the predominant sites of pathogen entry and infection. Although numerous effective mucosal vaccines are in use, the use of these vaccines has not yet been translated into licensed mucosal vaccines and this is due to its solely live attenuated and inactivated whole-cell preparations. Therefore, this Special Issue in Vaccines reflects the research interest of scientific communities involved in studying therapeutics or prophylactic interventions against bacterial pathogens, infecting via mucosal barriers. Additionally, the development of mucosal bacterial vaccines will offer a potential fortification at the mucosal site of entry. Publication of scientific studies or potential research work focusing on vaccine development, host–pathogen interaction, establishment of protection innate and adaptive immune factors, and their mechanism of cross-talk will be considered equally.

Dr. Amit K. Singh
Dr. Raj Kumar
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • mucosal immunity
  • vaccine
  • toxoid
  • subunit vaccines/polysaccharide vaccines
  • inactive vaccines
  • live attenuated vaccine
  • recombinant vaccines

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Published Papers (6 papers)

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Research

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12 pages, 1668 KiB  
Article
MV140 Mucosal Vaccine Induces Targeted Immune Response for Enhanced Clearance of Uropathogenic E. coli in Experimental Urinary Tract Infection
by Paula Saz-Leal, Marianne Morris Ligon, Carmen María Diez-Rivero, Diego García-Ayuso, Soumitra Mohanty, Marcos Viñuela, Irene Real-Arévalo, Laura Conejero, Annelie Brauner, José Luis Subiza and Indira Uppugunduri Mysorekar
Vaccines 2024, 12(5), 535; https://doi.org/10.3390/vaccines12050535 - 14 May 2024
Cited by 1 | Viewed by 2073
Abstract
MV140 is an inactivated whole-cell bacterial mucosal vaccine with proven clinical efficacy against recurrent urinary tract infections (UTIs). These infections are primarily caused by uropathogenic E. coli (UPEC) strains, which are unique in their virulence factors and remarkably diverse. MV140 contains a non-UPEC [...] Read more.
MV140 is an inactivated whole-cell bacterial mucosal vaccine with proven clinical efficacy against recurrent urinary tract infections (UTIs). These infections are primarily caused by uropathogenic E. coli (UPEC) strains, which are unique in their virulence factors and remarkably diverse. MV140 contains a non-UPEC strain, suggesting that it may induce an immune response against different UPEC-induced UTIs in patients. To verify this, we experimentally evaluated the cellular and humoral responses to UTI89, a prototypical UPEC strain, in mice vaccinated with MV140, as well as the degree of protection achieved in a UPEC UTI89 model of acute cystitis. The results show that both cellular (Th1/Th17) and antibody (IgG/IgA) responses to UTI89 were induced in MV140-immunized mice. MV140 vaccination resulted in an early increased clearance of UTI89 viable bacteria in the bladder and urine following transurethral infection. This was accompanied by a highly significant increase in CD4+ T cells in the bladder and an increase in urinary neutrophils. Collectively, our results support that MV140 induces cross-reactive humoral and cellular immune responses and cross-protection against UPEC strains. Full article
(This article belongs to the Special Issue Bacterial Vaccine: Mucosal Immunity and Implications)
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20 pages, 4928 KiB  
Article
Further Evaluation of Enterohemorrhagic Escherichia coli Gold Nanoparticle Vaccines Utilizing Citrobacter rodentium as the Model Organism
by Sarah Bowser, Angela Melton-Celsa, Itziar Chapartegui-González and Alfredo G. Torres
Vaccines 2024, 12(5), 508; https://doi.org/10.3390/vaccines12050508 - 8 May 2024
Viewed by 1728
Abstract
Enterohemorrhagic E. coli (EHEC) is a group of pathogenic bacteria that is associated with worldwide human foodborne diarrheal illnesses and the development of hemolytic uremic syndrome, a potentially deadly condition associated with Shiga toxins (Stxs). Currently, approved vaccines for human prophylaxis against infection [...] Read more.
Enterohemorrhagic E. coli (EHEC) is a group of pathogenic bacteria that is associated with worldwide human foodborne diarrheal illnesses and the development of hemolytic uremic syndrome, a potentially deadly condition associated with Shiga toxins (Stxs). Currently, approved vaccines for human prophylaxis against infection do not exist, and one barrier preventing the successful creation of EHEC vaccines is the absence of dependable animal models, including mice, which are naturally resistant to EHEC infection and do not manifest the characteristic signs of the illness. Our lab previously developed gold nanoparticle (AuNP)-based EHEC vaccines, and assessed their efficacy using Citrobacter rodentium, which is the mouse pathogen counterpart of EHEC, along with an Stx2d-producing strain that leads to more consistent disease kinetics in mice, including lethality. The purpose of this study was to continue evaluating these vaccines to increase protection. Here, we demonstrated that subcutaneous immunization of mice with AuNPs linked to the EHEC antigens EscC and intimin (Eae), either alone or simultaneously, elicits functional robust systemic humoral responses. Additionally, vaccination with both antigens together showed some efficacy against Stx2d-producing C. rodentium while AuNP-EscC successfully limited infection with non-Stx2d-producing C. rodentium. Overall, the collected results indicate that our AuNP vaccines have promising potential for preventing disease with EHEC, and that evaluation of novel vaccines using an appropriate animal model, like C. rodentium described here, could be the key to finally developing an effective EHEC vaccine that can progress into human clinical trials. Full article
(This article belongs to the Special Issue Bacterial Vaccine: Mucosal Immunity and Implications)
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17 pages, 2319 KiB  
Article
Bacterium-like Particles from Corynebacterium pseudodiphtheriticum as Mucosal Adjuvant for the Development of Pneumococcal Vaccines
by Ramiro Ortiz Moyano, Fernanda Raya Tonetti, Mariano Elean, Yoshiya Imamura, Kohtaro Fukuyama, Yoshihito Suda, Vyacheslav Melnikov, Alexander Suvorov, María Guadalupe Vizoso-Pinto, Haruki Kitazawa and Julio Villena
Vaccines 2024, 12(4), 412; https://doi.org/10.3390/vaccines12040412 - 12 Apr 2024
Viewed by 1486
Abstract
Previously, it was shown that intranasally (i.n.) administered Corynebacterium pseudodiphtheriticum 090104 (Cp) or CP-derived bacterium-like particles (BLPs) improve the immunogenicity of the pneumococcal conjugate vaccine (PCV). This work aimed to deepen the characterization of the adjuvant properties of Cp and CP-derived BLPs for [...] Read more.
Previously, it was shown that intranasally (i.n.) administered Corynebacterium pseudodiphtheriticum 090104 (Cp) or CP-derived bacterium-like particles (BLPs) improve the immunogenicity of the pneumococcal conjugate vaccine (PCV). This work aimed to deepen the characterization of the adjuvant properties of Cp and CP-derived BLPs for their use in the development of pneumococcal vaccines. The ability of Cp and CP-derived BLPs to improve both the humoral and cellular specific immune responses induced by i.n. administered polysaccharide-based commercial pneumococcal vaccine (Pneumovax 23®) and the chimeric recombinant PSPF (PsaA-Spr1875-PspA-FliC) protein was evaluated, as well as the protection against Streptococcus pneumoniae infection in infant mice. Additionally, whether the immunization protocols, including Cp and CP-derived BLPs, together with the pneumococcal vaccines can enhance the resistance to secondary pneumococcal pneumonia induced after inflammatory lung damage mediated by the activation of Toll-like receptor 3 (TLR3) was assessed. The results showed that both Cp and CP-derived BLPs increased the immunogenicity and protection induced by two pneumococcal vaccines administered through the nasal route. Of note, the nasal priming with the PSPF T-dependent antigen co-administered with Cp or CP-derived BLPs efficiently stimulated humoral and cellular immunity and increased the resistance to primary and secondary pneumococcal infections. The CP-derived BLPs presented a stronger effect than live bacteria. Given safety concerns associated with live bacterium administration, especially in high-risk populations, such as infants, the elderly, and immunocompromised patients, BLPs emerge as an attractive mucosal adjuvant to improve the host response to pneumococcal infections and to enhance the vaccines already in the market or in development. Full article
(This article belongs to the Special Issue Bacterial Vaccine: Mucosal Immunity and Implications)
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18 pages, 2396 KiB  
Article
Recombinant Salmonella gallinarum (S. gallinarum) Vaccine Candidate Expressing Avian Pathogenic Escherichia coli Type I Fimbriae Provides Protections against APEC O78 and O161 Serogroups and S. gallinarum Infection
by Peng Dai, Hucong Wu, Guowei Ding, Juan Fan, Yuhe Li, Shoujun Li, Endong Bao, Yajie Li, Xiaolei Gao, Huifang Li, Chunhong Zhu and Guoqiang Zhu
Vaccines 2023, 11(12), 1778; https://doi.org/10.3390/vaccines11121778 - 28 Nov 2023
Cited by 2 | Viewed by 1873
Abstract
Avian pathogenic Escherichia coli (APEC) is one of the leading pathogens that cause devastating economic losses to the poultry industry. Type I fimbriae are essential adhesion factors of APEC, which can be targeted and developed as a vaccine candidate against multiple APEC serogroups [...] Read more.
Avian pathogenic Escherichia coli (APEC) is one of the leading pathogens that cause devastating economic losses to the poultry industry. Type I fimbriae are essential adhesion factors of APEC, which can be targeted and developed as a vaccine candidate against multiple APEC serogroups due to their excellent immunogenicity and high homology. In this study, the recombinant strain SG102 was developed by expressing the APEC type I fimbriae gene cluster (fim) on the cell surface of an avirulent Salmonella gallinarum (S. gallinarum) vector strain using a chromosome-plasmid-balanced lethal system. The expression of APEC type I fimbriae was verified by erythrocyte hemagglutination assays and antigen-antibody agglutination tests. In vitro, the level of the SG102 strain adhering to leghorn male hepatoma (LMH) cells was significantly higher than that of the empty plasmid control strain, SG101. At two weeks after oral immunization, the SG102 strain remained detectable in the livers, spleens, and ceca of SG102-immunized chickens, while the SG101 strain was eliminated in SG101-immunized chickens. At 14 days after the secondary immunization with 5 × 109 CFU of the SG102 strain orally, highly antigen-specific humoral and mucosal immune responses against APEC type I fimbriae protein were detected in SG102-immunized chickens, with IgG and secretory IgA (sIgA) concentrations of 221.50 μg/mL and 1.68 μg/mL, respectively. The survival rates of SG102-immunized chickens were 65% (13/20) and 60% (12/20) after challenge with 50 LD50 doses of APEC virulent strains O78 and O161 serogroups, respectively. By contrast, 95% (19/20) and 100% (20/20) of SG101-immunized chickens died in challenge studies involving APEC O78 and O161 infections, respectively. In addition, the SG102 strain effectively provided protection against lethal challenges from the virulent S. gallinarum strain. These results demonstrate that the SG102 strain, which expresses APEC type I fimbriae, is a promising vaccine candidate against APEC O78 and O161 serogroups as well as S. gallinarum infections. Full article
(This article belongs to the Special Issue Bacterial Vaccine: Mucosal Immunity and Implications)
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18 pages, 2765 KiB  
Article
Mucosal Vaccination with Live Attenuated Bordetella bronchiseptica Protects against Challenge in Wistar Rats
by Beatriz Miguelena Chamorro, Karelle De Luca, Gokul Swaminathan, Nicolas Rochereau, Jade Majorel, Hervé Poulet, Blandine Chanut, Lauriane Piney, Egbert Mundt and Stéphane Paul
Vaccines 2023, 11(5), 982; https://doi.org/10.3390/vaccines11050982 - 15 May 2023
Cited by 2 | Viewed by 2951
Abstract
Bordetella bronchiseptica (Bb) is a Gram-negative bacterium responsible for canine infectious respiratory disease complex (CIRDC). Several vaccines targeting this pathogen are currently licensed for use in dogs, but their mechanism of action and the correlates of protection are not fully understood. To investigate [...] Read more.
Bordetella bronchiseptica (Bb) is a Gram-negative bacterium responsible for canine infectious respiratory disease complex (CIRDC). Several vaccines targeting this pathogen are currently licensed for use in dogs, but their mechanism of action and the correlates of protection are not fully understood. To investigate this, we used a rat model to examine the immune responses induced and the protection conferred by a canine mucosal vaccine after challenge. Wistar rats were vaccinated orally or intranasally on D0 and D21 with a live attenuated Bb vaccine strain. At D35, the rats of all groups were inoculated with 103 CFU of a pathogenic strain of B. bronchiseptica. Animals vaccinated via either the intranasal or the oral route had Bb-specific IgG and IgM in their serum and Bb-specific IgA in nasal lavages. Bacterial load in the trachea, lung, and nasal lavages was lower in vaccinated animals than in non-vaccinated control animals. Interestingly, coughing improved in the group vaccinated intranasally, but not in the orally vaccinated or control group. These results suggest that mucosal vaccination can induce mucosal immune responses and provide protection against a Bb challenge. This study also highlights the advantages of a rat model as a tool for studying candidate vaccines and routes of administration for dogs. Full article
(This article belongs to the Special Issue Bacterial Vaccine: Mucosal Immunity and Implications)
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Review

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22 pages, 1693 KiB  
Review
Mucosal Vaccination Strategies against Clostridioides difficile Infection
by Joshua Heuler, Harish Chandra and Xingmin Sun
Vaccines 2023, 11(5), 887; https://doi.org/10.3390/vaccines11050887 - 23 Apr 2023
Cited by 6 | Viewed by 3598
Abstract
Clostridioides difficile infection (CDI) presents a major public health threat by causing frequently recurrent, life-threatening cases of diarrhea and intestinal inflammation. The ability of C. difficile to express antibiotic resistance and to form long-lasting spores makes the pathogen particularly challenging to eradicate from [...] Read more.
Clostridioides difficile infection (CDI) presents a major public health threat by causing frequently recurrent, life-threatening cases of diarrhea and intestinal inflammation. The ability of C. difficile to express antibiotic resistance and to form long-lasting spores makes the pathogen particularly challenging to eradicate from healthcare settings, raising the need for preventative measures to curb the spread of CDI. Since C. difficile utilizes the fecal–oral route of transmission, a mucosal vaccine could be a particularly promising strategy by generating strong IgA and IgG responses that prevent colonization and disease. This mini-review summarizes the progress toward mucosal vaccines against C. difficile toxins, cell–surface components, and spore proteins. By assessing the strengths and weaknesses of particular antigens, as well as methods for delivering these antigens to mucosal sites, we hope to guide future research toward an effective mucosal vaccine against CDI. Full article
(This article belongs to the Special Issue Bacterial Vaccine: Mucosal Immunity and Implications)
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