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3. The 2022 Vaccines Against Shigella and Enterotoxigenic Escherichia coli (VASE) Conference: Summary of breakout workshops

Author

Baqar, Shahida, Bonavia, Aurelio, Louis Bourgeois, A., Campo, Joseph J.J., Clifford, Allison, Hanevik, Kurt, Hasso-Agopsowicz, Mateusz, Hausdorff, William, Kaminski, Robert, Maclennan, Calman Alexander, Mantis, Nicholas, Martin, Laura L.B., Omore, Richard, Pasetti, Marcela M.F., Pavlinac, Patricia, Phalipon, Armelle, Poly, Frédéric, Porter, Chad C.K., Ramasamy, Maheshi M.N., Rogawski McQuade, Elizabeth E.T., Sztein, Marcelo M.B., Walker, Richard Isley, Baqar, Shahida, Bonavia, Aurelio, Louis Bourgeois, A., Campo, Joseph J.J., Clifford, Allison, Hanevik, Kurt, Hasso-Agopsowicz, Mateusz, Hausdorff, William, Kaminski, Robert, Maclennan, Calman Alexander, Mantis, Nicholas, Martin, Laura L.B., Omore, Richard, Pasetti, Marcela M.F., Pavlinac, Patricia, Phalipon, Armelle, Poly, Frédéric, Porter, Chad C.K., Ramasamy, Maheshi M.N., Rogawski McQuade, Elizabeth E.T., Sztein, Marcelo M.B., and Walker, Richard Isley

Abstract

The global public health nonprofit organization PATH hosted the third Vaccines Against Shigella and Enterotoxigenic Escherichia coli (VASE) Conference in Washington, DC, from November 29 to December 1, 2022. This international gathering focused on cutting-edge research related to the development of vaccines against neglected diarrheal pathogens including Shigella, enterotoxigenic Escherichia coli (ETEC), Campylobacter, and non-typhoidal Salmonella. In addition to the conference's plenary content, the agenda featured ten breakout workshops on topics of importance to the enteric vaccine field. This unique aspect of VASE Conferences allows focused groups of attendees to engage in in-depth discussions on subjects of interest to the enteric vaccine development community. In 2022, the workshops covered a range of topics. Two focused on the public health value of enteric vaccines, with one examining how to translate evidence into policy and the other on the value proposition of potential combination vaccines against bacterial enteric pathogens. Two more workshops explored new tools for the development and evaluation of vaccines, with the first on integrating antigen/antibody technologies for mucosal vaccine and immunoprophylactic development, and the second on adjuvants specifically for Shigella vaccines for children in low- and middle-income countries. Another pair of workshops covered the status of vaccines against two emerging enteric pathogens, Campylobacter and invasive non-typhoidal Salmonella. The remaining four workshops examined the assessment of vaccine impact on acute and long-term morbidity. These included discussions on the nature and severity of intestinal inflammation; cellular immunity and immunological memory in ETEC and Shigella infections; clinical and microbiologic endpoints for Shigella vaccine efficacy studies in children; and intricacies of protective immunity to enteric pathogens. This article provides a brief summary of the presentations and discus, SCOPUS: cp.j, info:eu-repo/semantics/published

Published
2024

4. Repeat modules and N-linked glycans define structure and antigenicity of a critical enterotoxigenic E. coli adhesin.

Author

Berndsen, Zachary T., Akhtar, Marjahan, Thapa, Mahima, Vickers, Tim J., Schmitz, Aaron, Torres, Jonathan L., Baboo, Sabyasachi, Kumar, Pardeep, Khatoon, Nazia, Sheikh, Alaullah, Hamrick, Melissa, Diedrich, Jolene K., Martinez-Bartolome, Salvador, Garrett, Patrick T., Yates III, John R., Turner, Jackson S., Laird, Renee M., Poly, Frédéric, Porter, Chad K., and Copps, Jeffrey

Subjects
BLOOD groups, ESCHERICHIA coli, GLYCAN structure, INTESTINAL mucosa, BACTERIAL adhesion, IMMUNOGLOBULINS, MONOCLONAL antibodies
Abstract

Enterotoxigenic Escherichia coli (ETEC) cause hundreds of millions of cases of infectious diarrhea annually, predominantly in children from low-middle income regions. Notably, in children, as well as volunteers challenged with ETEC, diarrheal severity is significantly increased in blood group A (bgA) individuals. EtpA, is a secreted glycoprotein adhesin that functions as a blood group A lectin to promote critical interactions between ETEC and blood group A glycans on intestinal epithelia for effective bacterial adhesion and toxin delivery. EtpA is highly immunogenic resulting in robust antibody responses following natural infection and experimental challenge of volunteers with ETEC. To understand how EtpA directs ETEC-blood group A interactions and stimulates adaptive immunity, we mutated EtpA, mapped its glycosylation by mass-spectrometry (MS), isolated polyclonal (pAbs) and monoclonal antibodies (mAbs) from vaccinated mice and ETEC-infected volunteers, and determined structures of antibody-EtpA complexes by cryo-electron microscopy. Both bgA and mAbs that inhibited EtpA-bgA interactions and ETEC adhesion, bound to the C-terminal repeat domain highlighting this region as crucial for ETEC pathogen-host interaction. MS analysis uncovered extensive and heterogeneous N-linked glycosylation of EtpA and cryo-EM structures revealed that mAbs directly engage these unique glycan containing epitopes. Finally, electron microscopy-based polyclonal epitope mapping revealed antibodies targeting numerous distinct epitopes on N and C-terminal domains, suggesting that EtpA vaccination generates responses against neutralizing and decoy regions of the molecule. Collectively, we anticipate that these data will inform our general understanding of pathogen-host glycan interactions and adaptive immunity relevant to rational vaccine subunit design. Author summary: Enterotoxigenic E. coli (ETEC), a leading cause of diarrhea disproportionately affecting young children in low-income regions, are a priority for vaccine development. Individuals possessing A blood-type are more susceptible to severe cholera-like disease. EtpA, a secreted, immunogenic, blood group A binding protein, is a current vaccine target antigen. Here, we determined the structure of EtpA in complex with protective as well as non-protective monoclonal antibodies targeting two different domains of the protein, pinpointing key regions involved in blood-group A antigen recognition and uncovering the mechanism of antibody-based protection. In addition, we show through mass-spectrometry that EtpA is extensively and heterogeneously glycosylated at surface-exposed asparagine residues by a promiscuous and low-fidelity glycosyltransferase, EtpC, and that this unique form of bacterial glycosylation is critical for to development of protective immune responses. Lastly, polyclonal antibodies from vaccinated mice as well as monoclonal antibodies obtained from ETEC-infected volunteers revealed that the highly antigenic surface of EtpA exhibits both protective and non-protective epitopes. These results greatly expand our understanding of ETEC pathogenesis, and the immune responses elicited by these common infections, providing valuable information to aid in the rational design and testing of subunit vaccines. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Comprehensive Microbiological and Metagenomic Analysis of the Guillain–Barré Syndrome Outbreak in Lima, 2019.

Author

Rojas, Jesús D., Ramos, Mariana, Cruz, Cristopher, Long, Kyle A., Voegtly, Logan J., Meza, Rina, Espinoza, Nereyda, Ttito, Ana Ramos, Cáceres, Hugo Umeres, Cuentas, Alejandro Llanos, Meza, Yocelinda, Troncos, Gilda, Poly, Frédéric M., Paskey, Adrian C., Lueder, Matthew R., Rice, Gregory K., Cer, Regina Z., Bishop-Lilly, Kimberly A., Silva, María, and Grogl, Max

Subjects
GENOMICS, CAMPYLOBACTER jejuni, METAGENOMICS, PUBLIC health, MIXED infections
Abstract

In 2018/2019, two large Guillain–Barré Syndrome (GBS) outbreaks took place in Peru. Here, we report a comprehensive analysis of biological samples from GBS patients from the 2019 outbreak. We applied metagenomic, microbiologic, and serological analyses to different biological samples collected from GBS patients. Further phenotypic and genomic characterization was conducted on Campylobacter jejuni isolates from GBS samples. Microbiologic and metagenomic analyses revealed several patients with multiple co-infections, yet no common infectious agents were found other than C. jejuni. Four C. jejuni isolates were isolated from rectal swabs. Twenty-one patients had detectable IgG serum antibodies related to C. jejuni, of whom seven had IgM antibodies. Genomic analyses showed that these four strains were clonal (ST2993) and contained the class A lipooligosaccharide biosynthesis locus. These results further support the idea that that C. jejuni is the etiological agent that triggered the GBS outbreak in Peru in 2019 and that the strains are not restricted to Peru, hence could be regarded as a broad public health concern. Furthermore, though we cannot delineate the role played by co-infections in GBS development, results obtained herein highlight metagenomic analysis as a potential new tool for depicting a yet unknown area of research in GBS. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Bioactivity and efficacy of a hyperimmune bovine colostrum product- Travelan, against shigellosis in a non-Human primate model (Macaca mulatta)

Author

Islam, Dilara, primary, Ruamsap, Nattaya, additional, Imerbsin, Rawiwan, additional, Khanijou, Patchariya, additional, Gonwong, Siriphan, additional, Wegner, Matthew D., additional, McVeigh, Annette, additional, Poly, Frédéric M., additional, Crawford, John M., additional, Swierczewski, Brett E., additional, Kaminski, Robert W., additional, and Laird, Renee M., additional

Published
2023
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7. Enterotoxigenic E. coli virulence gene regulation in human infections

Author

Crofts, Alexander A., Giovanetti, Simone M., Rubin, Erica J., Poly, Frédéric M., Gutiérrez, Ramiro L., Talaat, Kawsar R., Porter, Chad K., Riddle, Mark S., DeNearing, Barbara, Brubaker, Jessica, Maciel, Milton, Alcala, Ashley N., Chakraborty, Subhra, Prouty, Michael G., Savarino, Stephen J., Davies, Bryan W., and Trent, M. Stephen

Published
2018

8. Rifaximin Fails to Prevent Campylobacteriosis in the Human Challenge Model : A Randomized, Double-Blind, Placebo-Controlled Trial

Author

Rimmer, Joanna E., Harro, Clayton, Sack, David A., Talaat, Kawsar R., Gutierrez, Ramiro L., DeNearing, Barbara, Brubaker, Jessica, Laird, Renee M., Poly, Frédéric, Maue, Alexander C., Jaep, Kayla, Alcala, Ashley, Mochalova, Yelizaveta, Gariepy, Christina L., Chakraborty, Subhra, Guerry, Patricia, Tribble, David R., Porter, Chad K., and Riddle, Mark S.

Published
2018

10. Campylobacter jejuni transcriptional and genetic adaptation during human infection

Author

Crofts, Alexander A., Poly, Frédéric M., Ewing, Cheryl P., Kuroiwa, Janelle M., Rimmer, Joanna E., Harro, Clayton, Sack, David, Talaat, Kawsar R., Porter, Chad K., Gutierrez, Ramiro L., DeNearing, Barbara, Brubaker, Jessica, Laird, Renée M., Maue, Alexander C., Jaep, Kayla, Alcala, Ashley, Tribble, David R., Riddle, Mark. S., Ramakrishnan, Amritha, McCoy, Andrea J., Davies, Bryan W., Guerry, Patricia, and Trent, M. Stephen

Published
2018
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14. Campylobacter jejuni Strain CG8421: A Refined Model for the Study of Campylobacteriosis and Evaluation of Campylobacter Vaccines in Human Subjects

Author

Tribble, David R., Baqar, Shahida, Carmolli, Marya P., Porter, Chad, Pierce, Kristen K., Sadigh, Katrin, Guerry, Patricia, Larsson, Catherine J., Rockabrand, David, Ventone, Cassandra H., Poly, Frederic, Lyon, Caroline E., Dakdouk, Sandra, Fingar, Ann, Gilliland, Theron, Daunais, Patrick, Jones, Erika, Rymarchyk, Stacia, Huston, Christopher, Darsley, Michael, and Kirkpatrick, Beth D.

Published
2009

15. Exploring Changes in the Host Gut Microbiota During a Controlled Human Infection Model for Campylobacter jejuni

Author

Stamps, Blake W., primary, Kuroiwa, Janelle, additional, Isidean, Sandra D., additional, Schilling, Megan A., additional, Harro, Clayton, additional, Talaat, Kawsar R., additional, Sack, David A., additional, Tribble, David R., additional, Maue, Alexander C., additional, Rimmer, Joanna E., additional, Laird, Renee M., additional, Porter, Chad K., additional, Goodson, Michael S., additional, and Poly, Frédéric, additional

Published
2021
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20. Application of a Campylobacter jejuni mouse infection model to test efficacy of a C. jejuni capsule conjugate vaccine delivered with a potent liposome adjuvant containing monophosphoryl lipid A and QS-21

Author

Laird, Renee M, primary, Gariepy, Christina L, additional, Eggleston, Heather, additional, Shoemaker, Nina M, additional, Monteiro, Mario A, additional, Guerry, Patricia, additional, Beck, Zoltan, additional, Matyas, Gary R, additional, and Poly, Frédéric, additional

Published
2020
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21. Distribution of Capsular Types of Campylobacter jejuni Isolates from Symptomatic and Asymptomatic Children in Peru

Author

Rojas, Jesús D., primary, Reynolds, Nathanael D., additional, Pike, Brian L., additional, Espinoza, Nereyda M., additional, Kuroiwa, Janelle, additional, Jani, Vihasi, additional, Ríos, Paul A., additional, Nunez, Rosa G., additional, Yori, Pablo P., additional, Bernal, Manuela, additional, Meza, Rina A., additional, Kosek, Margaret N., additional, McCoy, Andrea J., additional, Simons, Mark P., additional, Gregory, Michael J., additional, Guerry, Patricia, additional, and Poly, Frédéric M., additional

Published
2019
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22. Erratum for Ramakrishnan et al., “Enhanced Immunogenicity and Protective Efficacy of a Campylobacter jejuni Conjugate Vaccine Coadministered with Liposomes Containing Monophosphoryl Lipid A and QS-21”

Author

Ramakrishnan, Amritha, primary, Schumack, Nina M., additional, Gariepy, Christina L., additional, Eggleston, Heather, additional, Nunez, Gladys, additional, Espinoza, Nereyda, additional, Nieto, Monica, additional, Castillo, Rosa, additional, Rojas, Jesus, additional, McCoy, Andrea J., additional, Beck, Zoltan, additional, Matyas, Gary R., additional, Alving, Carl R., additional, Guerry, Patricia, additional, Poly, Frédéric, additional, and Laird, Renee M., additional

Published
2019
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23. Correction for Ramakrishnan et al., “Enhanced Immunogenicity and Protective Efficacy of a Campylobacter jejuni Conjugate Vaccine Coadministered with Liposomes Containing Monophosphoryl Lipid A and QS-21”

Author

Ramakrishnan, Amritha, primary, Schumack, Nina M., additional, Gariepy, Christina L., additional, Eggleston, Heather, additional, Nunez, Gladys, additional, Espinoza, Nereyda, additional, Nieto, Monica, additional, Castillo, Rosa, additional, Rojas, Jesus, additional, McCoy, Andrea J., additional, Beck, Zoltan, additional, Matyas, Gary R., additional, Alving, Carl R., additional, Guerry, Patricia, additional, Poly, Frédéric, additional, and Laird, Renee M., additional

Published
2019
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24. Enhanced Immunogenicity and Protective Efficacy of a Campylobacter jejuni Conjugate Vaccine Coadministered with Liposomes Containing Monophosphoryl Lipid A and QS-21

Author

Ramakrishnan, Amritha, primary, Schumack, Nina M., additional, Gariepy, Christina L., additional, Eggleston, Heather, additional, Nunez, Gladys, additional, Espinoza, Nereyda, additional, Nieto, Monica, additional, Castillo, Rosa, additional, Rojas, Jesus, additional, McCoy, Andrea J., additional, Beck, Zoltan, additional, Matyas, Gary R., additional, Alving, Carl R., additional, Guerry, Patricia, additional, Poly, Frédéric, additional, and Laird, Renee M., additional

Published
2019
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26. Distribution of flagella secreted protein and integral membrane protein among Campylobacter jejuni isolated from Thailand

Author

Pootong Piyarat, Serichantalergs Oralak, Bodhidatta Ladaporn, Poly Frédéric, Guerry Patricia, and Mason Carl J

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Abstract Background Campylobacter jejuni, a gram-negative bacterium, is a frequent cause of gastrointestinal food-borne illness in humans throughout the world. There are several reports that the virulence of C. jejuni might be modulated by non-flagellar proteins that are secreted through the filament. Recently, FspA (Flagella secreted proteins) have been described. Two alleles of fspA (fspA1 and fspA2) based on sequence analysis were previously reported and only the fspA2 allele was found in Thai isolates. The aim of this study is to analyze the deduced amino acid sequences fspA and the adjacent putative integral membrane protein from 103 Thai C. jejuni isolates. Results A total of 103 representative C. jejuni isolates were amplified by PCR for the fspA gene and the adjacent integral membrane protein gene. Two PCR product sizes were amplified using the same primers, an approximately 1600-bp PCR product from 19 strains that contained fspA and integral membrane protein genes and an approximately 800-bp PCR product from 84 strains that contained only the fspA gene. DNA sequencing was performed on the amplified products. The deduced amino acid sequences of both genes were analyzed separately using CLC Free Workbench 4 software. The analysis revealed three groups of FspA. Only FspA group 1 sequences (19/103) (corresponding to fspA1) consisting of 5 subgroups were associated with the adjacent gene encoding the integral membrane protein. FspA group 2 was the largest group (67/103) consisting of 9 subgroups. FspA group 2p (17/103) consisting of 7 subgroups was found to contain stop codons at a position before the terminal 142 position. Conclusions This study reveals greater heterogeneity of FspA (group 1, 2 and 2p) among Thai C. jejuni isolates than previously reported. Furthermore, the subgroups of FspA groups 1 were associated with groups of integral membrane protein. The significance of these different FspA variants to virulence requires further study.

Published
2011
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29. Evaluation of a conjugate vaccine platform against enterotoxigenic Escherichia coli (ETEC), Campylobacter jejuni and Shigella

Author

Laird, Renee M., primary, Ma, Zuchao, additional, Dorabawila, Nelum, additional, Pequegnat, Brittany, additional, Omari, Eman, additional, Liu, Yang, additional, Maue, Alexander C., additional, Poole, Steven T., additional, Maciel, Milton, additional, Satish, Kavyashree, additional, Gariepy, Christina L., additional, Schumack, Nina M., additional, McVeigh, Annette L., additional, Poly, Frédéric, additional, Ewing, Cheryl P., additional, Prouty, Michael G., additional, Monteiro, Mario A., additional, Savarino, Stephen J., additional, and Guerry, Patricia, additional

Published
2018
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31. Rifaximin Fails to Prevent Campylobacteriosis in the Human Challenge Model: A Randomized, Double-Blind, Placebo-Controlled Trial

Author

Rimmer, Joanna E, primary, Harro, Clayton, additional, Sack, David A, additional, Talaat, Kawsar R, additional, Gutierrez, Ramiro L, additional, DeNearing, Barbara, additional, Brubaker, Jessica, additional, Laird, Renee M, additional, Poly, Frédéric, additional, Maue, Alexander C, additional, Jaep, Kayla, additional, Alcala, Ashley, additional, Mochalova, Yelizaveta, additional, Gariepy, Christina L, additional, Chakraborty, Subhra, additional, Guerry, Patricia, additional, Tribble, David R, additional, Porter, Chad K, additional, and Riddle, Mark S, additional

Published
2017
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40. The Polysaccharide Capsule of Campylobacter jejuni Modulates the Host Immune Response

Author

Maue, Alexander C., primary, Mohawk, Krystle L., additional, Giles, David K., additional, Poly, Frédéric, additional, Ewing, Cheryl P., additional, Jiao, Yuening, additional, Lee, Ginyoung, additional, Ma, Zuchao, additional, Monteiro, Mario A., additional, Hill, Christina L., additional, Ferderber, Jason S., additional, Porter, Chad K., additional, Trent, M. Stephen, additional, and Guerry, Patricia, additional

Published
2013
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43. Characterization of Two Campylobacter jejuni Strains for Use in Volunteer Experimental-Infection Studies

Author

Poly, Frédéric, primary, Read, Timothy D., additional, Chen, Yu-Han, additional, Monteiro, Mario A., additional, Serichantalergs, Oralak, additional, Pootong, Piyarat, additional, Bodhidatta, Ladaporn, additional, Mason, Carl J., additional, Rockabrand, David, additional, Baqar, Shahida, additional, Porter, Chad K., additional, Tribble, David, additional, Darsley, Michael, additional, and Guerry, Patricia, additional

Published
2008
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50. High Frequency, Spontaneous motA Mutations in Campylobacter jejuni Strain 81-176.

Author

Mohawk, Krystle L., Poly, Frédéric, Sahl, Jason W., Rasko, David A., and Guerry, Patricia

Subjects
*CAMPYLOBACTER jejuni, *DIARRHEA, *LIPOOLIGOSACCHARIDES, *BACTERIAL evolution, *BACTERIAL mutation, *GRAM-negative bacteria, *BACTERIAL diseases
Abstract

Campylobacter jejuni is an important cause of bacterial diarrhea worldwide. The pathogenesis of C. jejuni is poorly understood and complicated by phase variation of multiple surface structures including lipooligosaccharide, capsule, and flagellum. When C. jejuni strain 81-176 was plated on blood agar for single colonies, the presence of translucent, non-motile colonial variants was noted among the majority of opaque, motile colonies. High-throughput genomic sequencing of two flagellated translucent and two opaque variants as well as the parent strain revealed multiple genetic changes compared to the published genome. However, the only mutated open reading frame common between the two translucent variants and absent from the opaque variants and the parent was motA, encoding a flagellar motor protein. A total of 18 spontaneous motA mutations were found that mapped to four distinct sites in the gene, with only one class of mutation present in a phase variable region. This study exemplifies the mutative/adaptive properties of C. jejuni and demonstrates additional variability in C. jejuni beyond phase variation. [ABSTRACT FROM AUTHOR]

Published
2014
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