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Microorganisms
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Vaccines against Human Enteric Bacterial Pathogens
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Vaccines against Human Enteric Bacterial Pathogens

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Antimicrobial Agents and Resistance".

Deadline for manuscript submissions: closed (31 May 2021) | Viewed by 18159

Special Issue Editors

Dr. Sjoerd Rijpkema

E-Mail Website
Guest Editor
Division of Bacteriology, NIBSC, South Mimms, Potters Bar EN63QG, UK
Interests: Enteric vaccines; pathogens; mucosal immunity; IVDs
Dr. Barbara Bolgiano

E-Mail Website
Guest Editor
Division of Bacteriology, NIBSC, South Mimms, Potters Bar EN63QG, UK
Interests: biophysical and biochemical methods for vaccine analysis

Special Issue Information

Dear Colleagues,

The landscape of enteric vaccines has changed dramatically with the success of new conjugate vaccines for typhoid, now being employed in mass vaccination campaigns in low and middle income countries targeting infants and children. This success comes out of a concerted action by the Bill and Melinda Gates Foundation, the Coalition against Typhoid and PATH, under the umbrella of WHO. This approach is regarded as a template for introducing new vaccines against shigellosis, paratyphoid, invasive non-typhoidal salmonella, campylobacter and ETEC. Now is an appropriate time to take stock of current developments and promising candidates in this field. This Special Issue will aim to focus on the immunogenicity and efficacy of enteric vaccines that are in the pre-clinical stage or the early clinical stage, e.g., the controlled human infection model, and on appropriate in vitro assays to ascertain potency and immunogenicity of these vaccines.

Dr. Sjoerd Rijpkema
Dr. Barbara Bolgiano
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. Microorganisms 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

  • Enteric vaccines
  • polysaccharide-conjugates
  • infants
  • antibody response
  • bactericidal antibodies
  • multi valent vaccines

Published Papers (7 papers)

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Editorial

Jump to: Research, Review

2 pages, 157 KiB  
Editorial
Recent Developments in Enteric Bacterial Vaccines
by Sjoerd Rijpkema and Barbara Bolgiano
Microorganisms 2021, 9(8), 1604; https://doi.org/10.3390/microorganisms9081604 - 28 Jul 2021
Viewed by 1885
Abstract
In this issue, we present promising developments in the field of bacterial enteric vaccines [...] Full article
(This article belongs to the Special Issue Vaccines against Human Enteric Bacterial Pathogens)

Research

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11 pages, 14666 KiB  
Article
Impact of O-Acetylation on S. flexneri 1b and 2a O-Antigen Immunogenicity in Mice
by Vanessa Arato, Davide Oldrini, Luisa Massai, Gianmarco Gasperini, Francesca Necchi and Francesca Micoli
Microorganisms 2021, 9(11), 2360; https://doi.org/10.3390/microorganisms9112360 - 15 Nov 2021
Cited by 8 | Viewed by 1589
Abstract
Shigellosis is a diarrheal disease caused prevalently by Shigella flexneri and S. sonnei and representing a major global health risk, particularly in developing countries. Bacterial O-antigen (OAg) is the primary target of the host immune response and modifications of its oligosaccharide units, including [...] Read more.
Shigellosis is a diarrheal disease caused prevalently by Shigella flexneri and S. sonnei and representing a major global health risk, particularly in developing countries. Bacterial O-antigen (OAg) is the primary target of the host immune response and modifications of its oligosaccharide units, including O-acetylation, are responsible for the variability among the circulating S. flexneri serotypes. No vaccines are widely available against shigellosis and the understanding of the immunogenicity induced by the OAg is fundamental for the design of a vaccine that could cover the most prevalent Shigella serotypes. To understand whether a different O-acetylation pattern could influence the immune response elicited by S. flexneri OAg, we employed as a vaccine technology GMMA purified from S. flexneri 2a and 1b strains that were easily engineered to obtain differently O-acetylated OAg. Resulting GMMA were tested in mice, demonstrating not only no major impact of O-acetyl decorations on the immune response elicited by the two OAg against the homologous strains, but also that the O-acetylation of the Rhamnose III residue (O-factor 9), shared among serotypes 1b, 2a and 6, does not induce cross-reactive antibodies against these serotypes. This work contributes to the optimization of vaccine design against Shigella, providing indication about the ability of shared epitopes to elicit broad protection against S. flexneri serotypes and supporting the identification of critical quality attributes of OAg-based vaccines. Full article
(This article belongs to the Special Issue Vaccines against Human Enteric Bacterial Pathogens)
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10 pages, 1247 KiB  
Article
Evidence of Extended Thermo-Stability of Typhoid Polysaccharide Conjugate Vaccines
by Fang Gao, Kay Lockyer, Alastair Logan, Sarah Davis, Barbara Bolgiano, Sjoerd Rijpkema, Gopal Singh, Sai D. Prasad, Samuel Pradeep Dondapati and Gurbaksh Singh Sounkhla
Microorganisms 2021, 9(8), 1707; https://doi.org/10.3390/microorganisms9081707 - 11 Aug 2021
Viewed by 2482
Abstract
Typhoid conjugate vaccines (TCV) are effective in preventing enteric fever caused by Salmonella enterica serovar Typhi in Southeast Asia and Africa. To facilitate vaccination with the Vi capsular polysaccharide–tetanus toxoid conjugate vaccine, Typbar TCV, and allow it to be transported and stored outside [...] Read more.
Typhoid conjugate vaccines (TCV) are effective in preventing enteric fever caused by Salmonella enterica serovar Typhi in Southeast Asia and Africa. To facilitate vaccination with the Vi capsular polysaccharide–tetanus toxoid conjugate vaccine, Typbar TCV, and allow it to be transported and stored outside a cold chain just prior to administration, an extended controlled-temperature conditions (ECTC) study was performed to confirm the quality of the vaccine at 40 °C for 3 days at the end of its shelf-life (36 months at 2–8 °C). Studies performed in parallel by the vaccine manufacturer, Bharat Biotech International Limited, and an independent national control laboratory (NIBSC) monitored its stability-indicating parameters: O-acetylation of the Vi polysaccharide, integrity of the polysaccharide–protein conjugate, and its molecular size and pH. ECTC samples stored at 40 °C and 45 °C in comparison with control samples stored at 4 °C and 55 or 56 °C, were shown to have stable O-acetylation and pH; only very slight increases in the percentage of free saccharide and corresponding decreases in molecular size were observed. The deoxycholate method for precipitating conjugated polysaccharide was very sensitive to small incremental increases in percentage of free saccharide, in line with storage temperature and duration. This extended ECTC study demonstrated minimal structural changes to the Vi polysaccharide and conjugate vaccine and a stable formulation following extended exposure to elevated temperatures for the desired durations. This outcome supports the manufacturer’s ECTC claim for the vaccine to be allowed to be taken outside the cold chain before its administration. Full article
(This article belongs to the Special Issue Vaccines against Human Enteric Bacterial Pathogens)
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12 pages, 1509 KiB  
Article
Development and Comparison of a Panel of Modified CS17 Fimbrial Tip Adhesin Proteins as Components for an Adhesin-Based Vaccine against Enterotoxigenic Escherichia coli
by Yang Liu, Milton Maciel, Jr., Aisling O’Dowd, Steven T. Poole, Julianne E. Rollenhagen, Irina V. Etobayeva and Stephen J. Savarino
Microorganisms 2021, 9(8), 1646; https://doi.org/10.3390/microorganisms9081646 - 31 Jul 2021
Cited by 4 | Viewed by 1712
Abstract
Enterotoxigenic Escherichia coli (ETEC) is a leading cause of diarrhea in travelers and children in resource-limited countries. ETEC colonization factors, fimbrial tip adhesins and enterotoxins are key virulence factors, and thus have been studied as vaccine candidates. Some prevalent colonization factors, including CFA/I [...] Read more.
Enterotoxigenic Escherichia coli (ETEC) is a leading cause of diarrhea in travelers and children in resource-limited countries. ETEC colonization factors, fimbrial tip adhesins and enterotoxins are key virulence factors, and thus have been studied as vaccine candidates. Some prevalent colonization factors, including CFA/I and CS17, belong to the class 5 family. We previously found that passive oral administration of hyperimmune bovine colostral IgG (bIgG) raised against dscCfaE (donor strand complemented CFA/I tip adhesin) protected volunteers against CFA/I+ ETEC challenge, while anti-dscCsbD bIgG (CS17 tip adhesin) did not confer protection. These findings led us to develop and optimize a panel of alternative CsbD-based vaccine candidates based on allele matching and in silico protein engineering. Physicochemical characterizations revealed that an optimized vaccine candidate dscCsbDLSN139(P218A/G3) had the greatest thermal stability among the six tested dscCsbD adhesins, whereas the overall secondary structures and solubility of these adhesins had no obvious differences. Importantly, dscCsbDLSN139(P218A/G3) elicited significantly higher CS17+ ETEC hemagglutination inhibition titers in sera from mice intranasally immunized with the panel of dscCsbD adhesins, while no significant difference was observed among heterologous neutralizing titers. Our results strongly advocate for the incorporation of these modifications into a new generation of CsbD-based ETEC vaccine candidates. Full article
(This article belongs to the Special Issue Vaccines against Human Enteric Bacterial Pathogens)
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11 pages, 1099 KiB  
Article
A Salmonella Typhi Controlled Human Infection Study for Assessing Correlation between Bactericidal Antibodies and Protection against Infection Induced by Typhoid Vaccination
by Elizabeth Jones, Celina Jin, Lisa Stockdale, Christina Dold, Andrew J. Pollard and Jennifer Hill
Microorganisms 2021, 9(7), 1394; https://doi.org/10.3390/microorganisms9071394 - 28 Jun 2021
Cited by 6 | Viewed by 2777
Abstract
Vi-polysaccharide conjugate vaccines are efficacious against typhoid fever in children living in endemic settings, their recent deployment is a promising step in the control of typhoid fever. However, there is currently no accepted correlate of protection. IgG and IgA antibodies generated in response [...] Read more.
Vi-polysaccharide conjugate vaccines are efficacious against typhoid fever in children living in endemic settings, their recent deployment is a promising step in the control of typhoid fever. However, there is currently no accepted correlate of protection. IgG and IgA antibodies generated in response to Vi conjugate or Vi plain polysaccharide vaccination are important but there are no definitive protective titre thresholds. We adapted a luminescence-based serum bactericidal activity (SBA) for use with S. Typhi and assessed whether bactericidal antibodies induced by either Vi tetanus toxoid conjugate (Vi-TT) or Vi plain polysaccharide (Vi-PS) were associated with protection in a controlled human infection model of typhoid fever. Both Vi-PS and Vi-TT induced significant increase in SBA titre after 28 days (Vi-PS; p < 0.0001, Vi-TT; p = 0.003), however higher SBA titre at the point of challenge did not correlate with protection from infection or reduced symptom severity. We cannot eliminate the role of SBA as part of a multifactorial immune response which protects against infection, however, our results do not support a strong role for SBA as a mechanism of Vi vaccine mediated protection in the CHIM setting. Full article
(This article belongs to the Special Issue Vaccines against Human Enteric Bacterial Pathogens)
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12 pages, 1923 KiB  
Article
Development of a Monocyte Activation Test as an Alternative to the Rabbit Pyrogen Test for Mono- and Multi-Component Shigella GMMA-Based Vaccines
by Danielle Carson, Sophie Myhill, Elena Palmieri, Francesca Necchi, Sjoerd Rijpkema, Francesca Micoli, Ida Karin Nordgren, Omar Rossi and Caroline Vipond
Microorganisms 2021, 9(7), 1375; https://doi.org/10.3390/microorganisms9071375 - 24 Jun 2021
Cited by 6 | Viewed by 3397
Abstract
Generalised modules for membrane antigens (GMMA)-based vaccines comprise the outer membrane from genetically modified Gram-negative bacteria containing membrane proteins, phospholipids and lipopolysaccharides. Some lipoproteins and lipopolysaccharides are pyrogens; thus, GMMA-based vaccines are intrinsically pyrogenic. It is important to control the pyrogenic content of [...] Read more.
Generalised modules for membrane antigens (GMMA)-based vaccines comprise the outer membrane from genetically modified Gram-negative bacteria containing membrane proteins, phospholipids and lipopolysaccharides. Some lipoproteins and lipopolysaccharides are pyrogens; thus, GMMA-based vaccines are intrinsically pyrogenic. It is important to control the pyrogenic content of biological medicines, including vaccines, to prevent adverse reactions such as febrile responses. The rabbit pyrogen test (RPT) and bacterial endotoxin test (BET) are the most commonly employed safety assays used to detect pyrogens. However, both tests are tailored for detecting pyrogenic contaminants and have considerable limitations when measuring the pyrogen content of inherently pyrogenic products. We report the adaptation of the monocyte activation test (MAT) as an alternative to the RPT for monitoring the pyrogenicity of Shigella GMMA-based vaccines. The European Pharmacopoeia endorses three MAT methods (A–C). Of these, method C, the reference lot comparison test, was identified as the most suitable. This method was evaluated with different reference materials to ensure parallelism and consistency for a mono- and multi-component Shigella GMMA vaccine. We demonstrate the drug substance as a promising reference material for safety testing of the matched drug product. Our results support the implementation of MAT as an alternative to the RPT and use of the defined parameters can be extended to GMMA-based vaccines currently in development, aiding vaccine batch release. Full article
(This article belongs to the Special Issue Vaccines against Human Enteric Bacterial Pathogens)
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Review

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24 pages, 1379 KiB  
Review
Vaccines for Protecting Infants from Bacterial Causes of Diarrheal Disease
by Richard Walker, Robert W. Kaminski, Chad Porter, Robert K. M. Choy, Jessica A. White, James M. Fleckenstein, Fred Cassels and Louis Bourgeois
Microorganisms 2021, 9(7), 1382; https://doi.org/10.3390/microorganisms9071382 - 25 Jun 2021
Cited by 23 | Viewed by 3484
Abstract
The global diarrheal disease burden for Shigella, enterotoxigenic Escherichia coli (ETEC), and Campylobacter is estimated to be 88M, 75M, and 75M cases annually, respectively. A vaccine against this target trio of enteric pathogens could address about one-third of diarrhea cases in children. [...] Read more.
The global diarrheal disease burden for Shigella, enterotoxigenic Escherichia coli (ETEC), and Campylobacter is estimated to be 88M, 75M, and 75M cases annually, respectively. A vaccine against this target trio of enteric pathogens could address about one-third of diarrhea cases in children. All three of these pathogens contribute to growth stunting and have demonstrated increasing resistance to antimicrobial agents. Several combinations of antigens are now recognized that could be effective for inducing protective immunity against each of the three target pathogens in a single vaccine for oral administration or parenteral injection. The vaccine combinations proposed here would result in a final product consistent with the World Health Organization’s (WHO) preferred product characteristics for ETEC and Shigella vaccines, and improve the vaccine prospects for support from Gavi, the Vaccine Alliance, and widespread uptake by low- and middle-income countries’ (LMIC) public health stakeholders. Broadly protective antigens will enable multi-pathogen vaccines to be efficiently developed and cost-effective. This review describes how emerging discoveries for each pathogen component of the target trio could be used to make vaccines, which could help reduce a major cause of poor health, reduced cognitive development, lost economic productivity, and poverty in many parts of the world. Full article
(This article belongs to the Special Issue Vaccines against Human Enteric Bacterial Pathogens)
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