Genetically detoxified tetanus toxin as a vaccine and conjugate carrier protein

Chang, Min-Ju; Ollivault‐Shiflett, Morgane; Schuman, Richard F.; Nguyen, Son; Kaltashov, Igor A.; Bobst, Cedric E.; Rajagopal, Shalini; Przedpelski, Amanda; Barbieri, Joseph T.; Lees, Andrew

doi:10.1016/j.vaccine.2022.07.011

Cited by 9 publications

(6 citation statements)

References 63 publications

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“…Anti-TT IgG responses were also assessed using TT as the coating antigen. Only TT was used, based on previous data showing the comparability of ELISA results using TT or 8MTT as coating antigens [ 24 ]. A decline in the anti-TT IgG response induced by 8MTT was evidenced after conjugation to both GAC and Vi, with statistical significance only for GAC ( Figure 3 A).…”

Section: Resultsmentioning

confidence: 99%

“…Indeed, TT is often purified prior to conjugation to obtain a monomeric fraction, because of the presence of aggregates and low purity. The 8MTT is, instead, already produced as a well-defined pure monomer that is ready for conjugation [ 24 ]. When TT is used without prior purification, the separation of unconjugated TT from the glycoconjugate can be more difficult to achieve, as verified here for GAC and Men oligosaccharides, and the glycoconjugate could contain fractions of unconjugated TT at a higher molecular weight ( Figure 2 ).…”

Section: Discussionmentioning

confidence: 99%

“…8MTT has already been produced at gram scale in E. coli and preliminary data have been generated by testing it as carrier, using the tick peptide P0 (which is under consideration as an immunogen for a cattle tick fever vaccine) and the capsular polysaccharide of Haemophilus influenzae type b (PRP) as antigens [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

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Testing a Recombinant Form of Tetanus Toxoid as a Carrier Protein for Glycoconjugate Vaccines

Oldrini,

Di Benedetto,

Carducci

et al. 2023

Vaccines

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Glycoconjugate vaccines play a major role in the prevention of infectious diseases worldwide, with significant impact on global health, enabling the polysaccharides to induce immunogenicity in infants and immunological memory. Tetanus toxoid (TT), a chemically detoxified bacterial toxin, is among the few carrier proteins used in licensed glycoconjugate vaccines. The recombinant full-length 8MTT was engineered in E. coli with eight individual amino acid mutations to inactivate three toxin functions. Previous studies in mice showed that 8MTT elicits a strong IgG response, confers protection, and can be used as a carrier protein. Here, we compared 8MTT to traditional carrier proteins TT and cross-reactive material 197 (CRM197), using different polysaccharides as models: Group A Streptococcus cell-wall carbohydrate (GAC), Salmonella Typhi Vi, and Neisseria meningitidis serogroups A, C, W, and Y. The persistency of the antibodies induced, the ability of the glycoconjugates to elicit booster response after re-injection at a later time point, the eventual carrier-induced epitopic suppression, and immune interference in multicomponent formulations were also evaluated. Overall, immunogenicity responses obtained with 8MTT glycoconjugates were compared to those obtained with corresponding TT and, in some cases, were higher than those induced by CRM197 glycoconjugates. Our results support the use of 8MTT as a good alternative carrier protein for glycoconjugate vaccines, with advantages in terms of manufacturability compared to TT.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Testing a Recombinant Form of Tetanus Toxoid as a Carrier Protein for Glycoconjugate Vaccines

Oldrini,

Di Benedetto,

Carducci

et al. 2023

Vaccines

Self Cite

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“…Patients who present with unclean wounds, who have not been su ciently immunized, or who have an unknown history of prior doses of tetanus toxoid should receive TIG and the tetanus toxoid vaccine. The early doses of the tetanus toxoid vaccine may prime the immune system, while TIG provides temporary immunity by removing the unbound tetanus toxin [97].…”

Section: Tetanusmentioning

confidence: 99%

Reported Bacterial Infectious Diseases in Saudi Arabia: Overview and Recent Advances

Alhumaid,

Alajmi,

Alosaimi

et al. 2023

Preprint

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Epidemiological surveillance is a critical tool to monitor the population's health and facilitate the prevention and control of infectious disease outbreaks. Bacterial infections are well known as one of the leading causes of global infection-related morbidity and mortality. Our study summarizes the number of bacterial infectious diseases in Saudi Arabia, along with an overview and recent advances in treatment or prevention modalities against these reported bacterial infections. This study only covers the reported bacterial infectious diseases in the Saudi Monthly Epidemiology Reports between 2018 and 2021. The results revealed that brucellosis, tuberculosis and salmonellosis were the most frequently reported bacterial infectious diseases in Saudi Arabia. Generally, males were more affected by bacterial infections than females. There was a variation in the distribution of bacterial infectious diseases between Saudi and non-Saudi citizens. Brucellosis and Salmonellosis infections were more common among Saudi citizens, while Tuberculosis was more common in non-Saudis. Interestingly, there was a decline in the incidence rates of numerous bacterial infectious diseases during the Coronavirus Disease 2019 (COVID-19) pandemic and COVID-19 restrictions. However, this decline in the incidence rates might be a result of underreporting during the national lockdown. Some bacterial infectious diseases were rarely reported in Saudi Arabia, including Syphilis, Diphtheria, and Guillain-Barré syndrome.

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“…Carrier proteins are applied to enhance the immunogenicity of the formulated antigens in vaccine formulae. The approved carrier proteins for human use include tetanus toxoid (TT), diphtheria toxoid (DT), Haemophilus protein D (PD), CRM197 (a nontoxic mutant of diphtheria toxin), and the outer membrane protein complex of serogroup B meningococcus (OMPC) [ 5 , 6 , 7 ]. TT, as a strong carrier protein, is composed of several T-cell peptides.…”

Section: Introductionmentioning

confidence: 99%

Potential Protectivity of a Conjugated COVID-19 Vaccine against Tetanus

Doroud,

Ashrafian,

Javadi

et al. 2024

Vaccines

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PastoCovac is a subunit protein vaccine against COVID-19 which contains the tetanus toxoid as a carrier conjugated to SARS-CoV-2 RBD. The primary goal of the tetanus application was to elicit a stronger specific response in the individuals. However, conjugate vaccines have the potency to generate anticarrier antibodies in addition to the target antigen. Therefore, the present study aimed to evaluate the PastoCovac vaccine in the humoral immune induction against tetanus. Six groups of individuals, including those who received one, two, or three doses of the PastoCovac vaccine, Td vaccine, and also the controls who received other COVID-19 vaccines (except PastoCovac), were investigated. The anti-tetanus IgG was assessed by an ELISA assay in all vaccinated groups. The antibody persistency against tetanus in the group who received one dose of the PastoCovac vaccine was also assessed on day 60, 90, and 180 after the last injection. The anti-tetanus antibody titer in the three groups of PastoCovac recipients was positive, though additional doses of the vaccine led to a significant antibody rise (p = 0.003). Notably, the comparison of the mean antibody titer between the Td recipients and those who received one/two doses of PastoCovac showed that the mean rise in the antibody titer before and after the injection was not significant. Although the antibody titer on day 180 decreased to a lower level than on day 21, it was still estimated to be highly positive against tetanus. Eventually, none of the PastoCovac recipients presented vaccine side-effects during the follow-up. The current data indicate that the tetanus conjugate vaccine against COVID-19, PastoCovac, could induce immune responses against tetanus, which can persist for at least 6 months. Combination vaccine formulae containing TT and DT as carriers for conjugate vaccines could be considered instead of TT and/or DT boosters in adults if they are indicated.

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Genetically detoxified tetanus toxin as a vaccine and conjugate carrier protein

Cited by 9 publications

References 63 publications

Testing a Recombinant Form of Tetanus Toxoid as a Carrier Protein for Glycoconjugate Vaccines

Testing a Recombinant Form of Tetanus Toxoid as a Carrier Protein for Glycoconjugate Vaccines

Reported Bacterial Infectious Diseases in Saudi Arabia: Overview and Recent Advances

Potential Protectivity of a Conjugated COVID-19 Vaccine against Tetanus

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