Proteomics, Bioinformatics and Structure-Function Antigen Mining For Gonorrhea Vaccines

Baarda, Benjamin I.; Martinez, Fabian G.; Sikora, Aleksandra E.

doi:10.3389/fimmu.2018.02793

Cited by 18 publications

(13 citation statements)

References 204 publications

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“…A similar approach based on reverse vaccinology has also been applied for the identification of vaccine targets in K. oxytoca , another closely related species to K. pneumoniae [76]. Furthermore, this approach has been adopted to target other gram-negative pathogens such as Acinetobacter baumannii [28,77], Pseudomonas aeruginosa [78], Neisseria gonorrhoeae [79], etc.…”

Section: Discussionmentioning

confidence: 99%

Immunoinformatics-Aided Design and Evaluation of a Potential Multi-Epitope Vaccine against Klebsiella Pneumoniae

et al. 2019

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Klebsiella pneumoniae is an opportunistic gram-negative bacterium that causes nosocomial infection in healthcare settings. Despite the high morbidity and mortality rate associated with these bacterial infections, no effective vaccine is available to counter the pathogen. In this study, the pangenome of a total of 222 available complete genomes of K. pneumoniae was explored to obtain the core proteome. A reverse vaccinology strategy was applied to the core proteins to identify four antigenic proteins. These proteins were then subjected to epitope mapping and prioritization steps to shortlist nine B-cell derived T-cell epitopes which were linked together using GPGPG linkers. An adjuvant (Cholera Toxin B) was also added at the N-terminal of the vaccine construct to improve its immunogenicity and a stabilized multi-epitope protein structure was obtained using molecular dynamics simulation. The designed vaccine exhibited sustainable and strong bonding interactions with Toll-like receptor 2 and Toll-like receptor 4. In silico reverse translation and codon optimization also confirmed its high expression in E. coli K12 strain. The computer-aided analyses performed in this study imply that the designed multi-epitope vaccine can elicit specific immune responses against K. pneumoniae. However, wet lab validation is necessary to further verify the effectiveness of this proposed vaccine candidate.

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Section: Discussionmentioning

confidence: 99%

Immunoinformatics-Aided Design and Evaluation of a Potential Multi-Epitope Vaccine against Klebsiella Pneumoniae

et al. 2019

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“…In the absence of an effective FDA-approved prophylactic against N. gonorrhoeae infections, new strategies are needed to expand the pool of candidates considered for potential clinical vaccine development. One innovative approach is reverse vaccinology antigen mining using a combination of high-throughput quantitative proteomics and bioinformatics (recently reviewed in [ 58 ]). The utility of proteomic technology has been clearly demonstrated in the discovery of N. gonorrhoeae lipoprotein MetQ (NGO2139).…”

Section: Resultsmentioning

confidence: 99%

Sexually Transmitted Neisseria gonorrhoeae Infections—Update on Drug Treatment and Vaccine Development

et al. 2021

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Background: Sexually transmitted gonorrhea, caused by the Gram-negative diplococcus Neisseria gonorrhoeae, continues to be a serious global health challenge despite efforts to eradicate it. Multidrug resistance among clinical N. gonorrhoeae isolates has limited treatment options, and attempts to develop vaccines have not been successful. Methods: A search of published literature was conducted, and information extracted to provide an update on the status of therapeutics and vaccine development for gonorrheal infection. Results: Recommended pharmacological treatment for gonorrhea has changed multiple times due to increasing acquisition of resistance to existing antibiotics by N. gonorrhoeae. Only broad-spectrum cephalosporin-based combination therapies are currently recommended for treatment of uncomplicated urogenital and anorectal gonococcal infections. With the reported emergence of ceftriaxone resistance, successful strategies addressing the global burden of gonorrhea must include vaccination. Century-old efforts at developing an effective vaccine against gonorrhea, leading to only four clinical trials, have not yielded any successful vaccine. Conclusions: While it is important to continue to explore new drugs for the treatment of gonorrhea, the historical trend of resistance acquisition suggests that any long-term strategy should include vaccine development. Advanced technologies in proteomics and in silico approaches to vaccine target identification may provide templates for future success.

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“…Using high-throughput proteomics and immunoblotting analyses, we previously reported that MetQ is ubiquitously expressed in diverse Ng isolates [13,28,29,31], in host-relevant growth conditions [13] and in naturally released outer membrane vesicles [13,28]. In addition to a traditional lipoprotein signal peptide, MetQ contains a NlpA domain homologous to the respective domain in the E. coli methionine binding protein MetQ, NlpA [14,32]. Indeed, Ng MetQ binds L-methionine with nanomolar affinity.…”

Section: Introductionmentioning

confidence: 99%

“…Serum or vaginal wash samples were serially diluted in PBS supplemented with 0.05% Tween (PBST) and added to each well. Polymorphism, phylogenetic, and allele mapping analyses were performed as described by[32], with the following exceptions. Briefly, the nucleotide sequence of metQ (ngo2139) was used to query the public Neisseria /pubmlst.org/neisseria/) to identify metQ alleles and nucleotide polymorphic sitesacross 4,421 isolates of N. gonorrhoeae for which metQ sequence data exist, as well as among all Neisseria isolates present in the database (21,798 isolates with metQ sequence data as of March 26, 2020).…”

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A novel gonorrhea vaccine composed of MetQ lipoprotein formulated with CpG shortens experimental murine infection

Sikora

Gomez

Van

et al. 2020

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23Bacterial surface lipoproteins are emerging as attractive vaccine candidates due to their 24 biological importance and the feasibility of their large-scale production for vaccine 25 manufacturing. The global prevalence of gonorrhea, resistance to antibiotics, and serious 26 consequences to reproductive and neonatal health necessitate development of effective 27 vaccines. Reverse vaccinology identified the surface-displayed L-methionine binding 28 lipoprotein MetQ (NGO2139) and its homolog GNA1946 (NMB1946) as gonococcal and 29 meningococcal vaccine candidates, respectively. Here, we assessed the suitability of 30 MetQ for inclusion in a gonorrhea vaccine by examining MetQ conservation, its function 31 in Neisseria gonorrhoeae (Ng) pathogenesis, and its ability to induce protective immune 32 responses using a female murine model of lower genital tract infection. In-depth 33 bioinformatics, phylogenetics and mapping the most prevalent Ng polymorphic amino 34 acids to the GNA1946 crystal structure revealed remarkable MetQ conservation: ~97% 35 Ng isolates worldwide possess a single MetQ variant. Mice immunized with rMetQ-CpG 36 (n=40), a vaccine containing a tag-free version of MetQ formulated with CpG, exhibited 37 robust, antigen-specific antibody responses in serum and at the vaginal mucosae 38 including secretory IgA. Consistent with the activity of CpG as a Th1-stimulating adjuvant, 39 the serum IgG1/IgG2a ratio of 0.38 indicated a Th1 bias. Combined data from two 40independent challenge experiments demonstrated that rMetQ-CpG immunized mice 41 cleared infection faster than control animals (vehicle, p<0.0001; CpG, p=0.002) and had 42 lower Ng burden (vehicle, p=0.03; CpG, p<0.0001). We conclude rMetQ-CpG induces a 43 protective immune response that accelerates bacterial clearance from the murine lower 44 genital tract and represents an attractive component of a gonorrhea subunit vaccine. 45 3

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Proteomics, Bioinformatics and Structure-Function Antigen Mining For Gonorrhea Vaccines

Cited by 18 publications

References 204 publications

Immunoinformatics-Aided Design and Evaluation of a Potential Multi-Epitope Vaccine against Klebsiella Pneumoniae

Immunoinformatics-Aided Design and Evaluation of a Potential Multi-Epitope Vaccine against Klebsiella Pneumoniae

Sexually Transmitted Neisseria gonorrhoeae Infections—Update on Drug Treatment and Vaccine Development

A novel gonorrhea vaccine composed of MetQ lipoprotein formulated with CpG shortens experimental murine infection

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