Proteomics of diphtheria toxoid vaccines reveals multiple proteins that are immunogenic and may contribute to protection of humans against Corynebacterium diphtheriae

Möller, Jens; Kraner, Max; Sonnewald, Uwe; Sangal, Vartul; Tittlbach, Hannes; Winkler, Julia; Winkler, Thomas; Mel'nikov, V. G.; Lang, Roland; Sing, Andreas; Mattos‐Guaraldi, Ana Luíza; Burkovski, Andreas

doi:10.1016/j.vaccine.2019.04.059

Cited by 29 publications

(33 citation statements)

References 58 publications

(61 reference statements)

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“…After considering the nature of bacterial vaccines, we discarded conjugate and polysaccharides vaccines and sought for potential sources of cross-reactive immunity in antigens identified by proteomics in DTa/wP and MenB vaccines. D and T antigens can vary between different vaccines, and here we considered the sum of all those reported elsewhere in (13,14,49). Our results, summarized in Table 4, indicate that combination DTP vaccines are significant sources of B and T cell cross-reactivity to SARS-CoV-2, while such cross-reactivity is small from MenB vaccine.…”

Section: Cross-reactive Immunity To Sars-cov-2 From Bacterial Vaccinementioning

confidence: 82%

“…In contrast, vaccines for N. meningitides serotype B (MenB) consist of surface proteins from N. meningitides (15). Diphteria (D) and tetanus (T) vaccines contain inactivated toxins produced by the bacteria (toxoids) but in addition include a large array of proteins as shown by proteomics studies, which can be immunogenic (14,49). D and T antigens are generally combined with pertussis (P) antigens as a combination DTP vaccine, which is available in two main formulations: DTaP and DTwP.…”

Section: Cross-reactive Immunity To Sars-cov-2 From Bacterial Vaccinementioning

confidence: 99%

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Potential Cross-Reactive Immunity to SARS-CoV-2 From Common Human Pathogens and Vaccines

Reche

2020

Front. Immunol.

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The recently emerged SARS-CoV-2 causing the ongoing COVID-19 pandemic is particularly virulent in the elderly while children are largely spared. Here, we explored the potential role of cross-reactive immunity acquired from pediatric vaccinations and exposure to common human pathogens in the protection and pathology of COVID-19. To that end, we sought for peptide matches to SARS-CoV-2 (identity ≥ 80%, in at least eight residues) in the proteomes of 25 human pathogens and in vaccine antigens, and subsequently predicted their T and B cell reactivity to identify potential cross-reactive epitopes. We found that viruses subject to pediatric vaccinations do not contain cross-reactive epitopes with SARS-CoV-2, precluding that they can provide any general protection against COVID-19. Likewise, common viruses including rhinovirus, respiratory syncytial virus, influenza virus, and several herpesviruses are also poor or null sources of cross-reactive immunity to SARS-CoV-2, discarding that immunological memory against these viruses can have any general protective or pathological role in COVID-19. In contrast, we found combination vaccines for treating diphtheria, tetanus, and pertussis infectious diseases (DTP vaccine) to be significant sources of potential cross-reactive immunity to SARS-CoV-2. DTP crossreactive epitopes with SARS-CoV-2 include numerous CD8 and CD4 T cell epitopes with broad population protection coverage and potentially neutralizing B cell epitopes in SARS-CoV-2 Spike protein. Worldwide, children receive several DTP vaccinations, including three-four doses the first year of life and one at 4-6 years of age. Moreover, a low antigenic Tdap dose is also given at ages 9-14. Thereby, children may well be protected from SARS-CoV-2 through cross-reactive immunity elicited by DTP vaccinations, supporting testing in the general population to prevent COVID-19.

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Section: Cross-reactive Immunity To Sars-cov-2 From Bacterial Vaccinementioning

confidence: 82%

Section: Cross-reactive Immunity To Sars-cov-2 From Bacterial Vaccinementioning

confidence: 99%

Potential Cross-Reactive Immunity to SARS-CoV-2 From Common Human Pathogens and Vaccines

Reche

2020

Front. Immunol.

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“…The cells were harvested by centrifugation. Protein extraction, separation of proteins by SDS gel electrophoresis and immuno-detection of diphtheria toxin with human serum were carried out as described previously (Möller et al 2019). RNA isolation and hybridization RNA isolation and hybridization was carried out as described previously (Ott et al 2010).…”

Section: Sds-page and Western Blottingmentioning

confidence: 99%

Phylogenomic characterisation of a novel corynebacterial species pathogenic to animals

Möller¹,

Musella²,

Mel'nikov³

et al. 2020

Antonie van Leeuwenhoek

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The genus Corynebacterium includes species of biotechnological, medical and veterinary importance. An atypical C. ulcerans strain, W25, was recently isolated from a case of necrotizing lymphadenitis in a wild boar. In this study, we have analysed the genome sequence of this strain and compared the phenotypic and virulence properties with other corynebacterial pathogens. Phylogenomic analyses revealed that strain W25 belongs to a novel species along with PO100/5 and KL1196. The latter strains were isolated from a pig and a roe deer, respectively; hence, this species appears to be associated to animals. The isolate W25 is likely a nontoxigenic tox gene bearing strain and may have compromised abilities to adhere to pharyngeal and laryngeal epithelial cells due to potential loss of the gene functions in spaBC and spaDEF pilus gene clusters. A number of corynebacterial virulence genes are present including pld encoding phospholipase D. Therefore, this strain may be able to cause severe invasive infections in animals and zoonotic infections in humans.

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“…(1) Several biophysical and immunochemical tests have been developed to assess the quality of toxoid-containing vaccines. 16,18,19,21,23,25,[27][28][29][30][31][32][33][34][35][36][37] These tests are valuable for examination of the purity, safety, potency, and stability of a product to reveal the impact of changes in a production process. 38,39 (2) Furthermore, the development of innovative vaccine formulations with diphtheria and tetanus toxoids has demanded detailed structural characterization of the toxoids.…”

Section: Introductionmentioning

confidence: 99%

Identification of Formaldehyde-Induced Modifications in Diphtheria Toxin

Metz

Michiels

Uittenbogaard

et al. 2020

Journal of Pharmaceutical Sciences

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Diphtheria toxoid is produced by detoxification of diphtheria toxin with formaldehyde. This study was performed to elucidate the chemical nature and location of formaldehyde-induced modifications in diphtheria toxoid. Diphtheria toxin was chemically modified using 4 different reactions with the following reagents: (1) formaldehyde and NaCNBH 3 , (2) formaldehyde, (3) formaldehyde and NaCNBH 3 followed by formaldehyde and glycine, and (4) formaldehyde and glycine. The modifications were studied by SDS-PAGE, primary amino group determination, and liquid chromatographyeelectrospray mass spectrometry of chymotryptic digests. Reaction 1 resulted in quantitative dimethylation of all lysine residues. Reaction 2 caused intramolecular cross-links, including the NAD þ-binding cavity and the receptor-binding site. Moreover, A fragments and B fragments were cross-linked by formaldehyde on part of the diphtheria toxoid molecules. Reaction 3 resulted in formaldehyde-glycine attachments, including in shielded areas of the protein. The detoxification reaction typically used for vaccine preparation (reaction 4) resulted in a combination of intramolecular cross-links and formaldehyde-glycine attachments. Both the NAD þ-binding cavity and the receptor-binding site of diphtheria toxin were chemically modified. Although CD4 þ T-cell epitopes were affected to some extent, one universal CD4 þ Tcell epitope remained almost completely unaltered by the treatment with formaldehyde and glycine.

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Proteomics of diphtheria toxoid vaccines reveals multiple proteins that are immunogenic and may contribute to protection of humans against Corynebacterium diphtheriae

Abstract: and Burkovski, Andreas (2019) Proteomics of diphtheria toxoid vaccines reveals multiple proteins that are immunogenic and may contribute to protection of humans against Corynebacterium diphtheriae. Vaccine, 37 (23). pp. 3061-3070.

Cited by 29 publications

References 58 publications

Potential Cross-Reactive Immunity to SARS-CoV-2 From Common Human Pathogens and Vaccines

Potential Cross-Reactive Immunity to SARS-CoV-2 From Common Human Pathogens and Vaccines

Phylogenomic characterisation of a novel corynebacterial species pathogenic to animals

Identification of Formaldehyde-Induced Modifications in Diphtheria Toxin

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