A GMMA-CPS-Based Vaccine for Non-Typhoidal Salmonella

Sokaribo, Akosiererem S.; Perera, Sumudu R; Sereggela, Zoe; Krochak, Ryan; Balezantis, Lindsay R.; Xing, Xiaohui; Lam, Shao Wei; Deck, William; Attah-Poku, Samuel K.; Abbott, D. Wade; Tamuly, Shantanu; White, Aaron P.

doi:10.3390/vaccines9020165

Cited by 8 publications

(8 citation statements)

References 83 publications

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“…The expansion of atypical Salmonella serovars in invasive infections is associated with a high health burden [ 17 , 38 ]. Invasive NTS vaccines in the pipeline may not cover all NTS serovars [ 50 ], and we identified several in this study, harbouring an assortment of virulence and antimicrobial resistance determinants. This points to the need for widespread and robust access to invasive Salmonella diagnostics in Nigeria to elucidate on the burden and make a case for serovar vaccine priorities [ 17 , 38 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

Genomic characterization of invasive typhoidal and non-typhoidal Salmonella in southwestern Nigeria

et al. 2022

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Background Salmonellosis causes significant morbidity and mortality in Africa. Information on lineages of invasive Salmonella circulating in Nigeria is sparse. Methods Salmonella enterica isolated from blood (n = 60) and cerebrospinal fluid (CSF, n = 3) between 2016 and 2020 from five tertiary hospitals in southwest Nigeria were antimicrobial susceptibility-tested and Illumina-sequenced. Genomes were analysed using publicly-available bioinformatic tools. Results Isolates and sequence types (STs) from blood were S. Typhi [ST1, n = 1 and ST2, n = 43] and invasive non-typhoidal Salmonella (iNTS) (S. Enteritidis [ST11, n = 7], S. Durham [ST10, n = 2], S. Rissen [ST8756, n = 2], S. Chester [ST2063, n = 1], S. Dublin [ST10, n = 1], S. Infantis [ST603, n = 1], S. Telelkebir [ST8757, n = 1] and S. Typhimurium [ST313, n = 1]). S. Typhi ST2 (n = 2) and S. Adabraka ST8757 (n = 1) were recovered from CSF. Most S. Typhi belonged to genotype 3.1.1 (n = 44), carried an IncY plasmid, had several antibiotic resistance genes (ARGs) including blaTEM-1 (n = 38), aph(6)-Id (n = 32), tet(A) (n = 33), sul2 (n = 32), dfrA14 (n = 30) as well as quinolone resistance-conferring gyrA_S83Y single-nucleotide polymorphisms (n = 37). All S. Enteritidis harboured aph(3”)-Ib, blaTEM-1, catA1, dfrA7, sul1, sul2, tet(B) genes, and a single ARG, qnrB19, was detected in S. Telelkebir. Typhoidal toxins cdtB, pltA and pltB were detected in S. Typhi, Rissen, Chester, and Telelkebir. Conclusion Most invasive salmonelloses in southwest Nigeria are vaccine-preventable infections due to multidrug-resistant, West African dominant S. Typhi lineage 3.1.1. Invasive NTS serovars, including some harbouring typhoidal toxin or resistance genes, represented a third of the isolates emphasizing the need for better diagnosis and surveillance.

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Section: Discussionmentioning

confidence: 99%

Genomic characterization of invasive typhoidal and non-typhoidal Salmonella in southwestern Nigeria

et al. 2022

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“…Salmonella O-Ag capsule was initially hypothesized to be a CPS that was distinct from very long chain LPS O-Ag and assembled by the yih operons [23]. However, in our recent study, we hypothesize that O-Ag capsule and very-long-chain LPS O-Ag are the same CPS and demonstrated that the yihUTSRQP operon is not directly involved in capsule assembly [47].…”

Section: Capsular Polysaccharides-salmonella and Other Selected Bacterial Speciesmentioning

confidence: 67%

“…The group 4 O-Antigen capsules were shown to be important for attachment to surfaces, colonization, and desiccation resistance [23]. S. Typhimurium O-Antigen capsule was shown to be expressed both at lower and higher temperatures indicating that the capsule may play a role in bacterial survival inside and outside the host, as described for other bacterial species, such as Hyphomonas strain MHS-3 [46,47]. Salmonella O-Ag capsule was initially hypothesized to be a CPS that was distinct from very long chain LPS O-Ag and assembled by the yih operons [23].…”

Section: Capsular Polysaccharides-salmonella and Other Selected Bacterial Speciesmentioning

confidence: 78%

“…In addition, the membrane components of GMMAs have adjuvant activity by codelivering multiple pathogen-associated molecular patterns (PAMPs) along with the target antigens [2]. In our hands, immunization of mice with GMMAs isolated from colanic acid overproducing strains was sufficient to significantly reduce Salmonella colonization [47]. It is possible that the development of a GMMA-CPS-based vaccine against NTS can be explored in the future.…”

Section: Other Vaccines Currently Being Developed For Ntsmentioning

confidence: 99%

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Polysaccharide Vaccines: A Perspective on Non-Typhoidal Salmonella

2021

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Polysaccharides are often the most abundant antigens found on the extracellular surfaces of bacterial cells. These polysaccharides play key roles in interactions with the outside world, and for many bacterial pathogens, they represent what is presented to the human immune system. As a result, many vaccines have been or currently are being developed against carbohydrate antigens. In this review, we explore the diversity of capsular polysaccharides (CPS) in Salmonella and other selected bacterial species and explain the classification and function of CPS as vaccine antigens. Despite many vaccines being developed using carbohydrate antigens, the low immunogenicity and the diversity of infecting strains and serovars present an antigen formulation challenge to manufacturers. Vaccines tend to focus on common serovars or have changing formulations over time, reflecting the trends in human infection, which can be costly and time-consuming. We summarize the approaches to generate carbohydrate-based vaccines for Salmonella, describe vaccines that are in development and emphasize the need for an effective vaccine against non-typhoidal Salmonella strains.

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“…The expansion of atypical Salmonella serovars in invasive infections is associated with a high health burden [17,36]. Invasive NTS vaccines in the pipeline may not cover all NTS serovars [50], and we identified several in this study, harbouring an assortment of virulence and antimicrobial resistance determinants. This points to the need for widespread and robust access to invasive Salmonella diagnostics in Nigeria to elucidate on the burden and make a case for serovar vaccine priorities [17,36,49].…”

Section: Discussionmentioning

confidence: 99%

Genomic characterization of invasive typhoidal and non-typhoidal Salmonella in southwestern Nigeria

Ikhimiukor

Oaikhena

Afolayan

et al. 2022

Preprint

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Background: Salmonellosis causes significant morbidity and mortality in Africa. Despite being endemic in Nigeria, information on circulating lineages of invasive Salmonella is sparse. Methods: Sixty-three Salmonella enterica isolated from blood (n=60) and cerebrospinal fluid (CSF, n=3) isolated between 2016 and 2020 from five tertiary hospitals in southwest Nigeria were Illumina-sequenced and analysed using publicly available bioinformatic tools. Results: Isolates and sequence types (STs) from blood were S. Typhi [ST1 =1 and ST2 =43] and invasive non-typhoidal Salmonella (iNTS) (S. Enteritidis [ST11, n=7], S. Durham [ST10, n=2], S. Rissen [ST8756, n=2], S. Chester [ST2063, n=1], S. Dublin [ST10, n=1], S. Infantis [ST603, n=1], S. Telelkebir [ST8757, n=1] and S. Typhimurium [ST313, n=1], whereas it was S. Typhi ST2 (n=2) and S. Adabraka ST8757 (n=1) from CSF. Most S. Typhi belonged to genotype 3.1.1 (n=44, 95.7%) and had several antibiotic resistance genes (ARGs) including blaTEM-1 (86.4%, n=38), aph(6)-Id (72.7%, n=32), tet(A) (75%, n=33), sul2 (72.7%, n=32), dfrA14 (68.18%, n=30) as well as the quinolone resistance-conferring gyrA_S83Y SNPs (n=37, 84.09%). The 3.1.1 strains included a predominant sub-lineage (n=33) harbouring gyrA_S83Y and an IncY plasmid detected at all hospitals. Typhoidal toxins cdtB, pltA and pltB were detected in S. Typhi, Rissen, Chester, and Telelkebir. Conclusion: This study revealed the West African dominant lineage 3.1.1 to be majority of S. Typhi genotype harbouring ARGs. The increasing number of iNTS, including serovars harbouring typhoidal toxins, as well as the dominance of multidrug resistant isolates emphasizes the need for better diagnosis and surveillance of invasive Salmonella.

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A GMMA-CPS-Based Vaccine for Non-Typhoidal Salmonella

Cited by 8 publications

References 83 publications

Genomic characterization of invasive typhoidal and non-typhoidal Salmonella in southwestern Nigeria

Genomic characterization of invasive typhoidal and non-typhoidal Salmonella in southwestern Nigeria

Polysaccharide Vaccines: A Perspective on Non-Typhoidal Salmonella

Genomic characterization of invasive typhoidal and non-typhoidal Salmonella in southwestern Nigeria

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