RNA gene profile variation in peripheral blood mononuclear cells from rhesus macaques immunized with Hib conjugate vaccine, Hib capsular polysaccharide and TT carrier protein

Tang, Jing; Zhang, Ying; Zhang, Xiaolong; Liao, Yun; Wang, Yongrong; Ouyang, Shengjie; Che, Yanchun; Xu, Miao; Pu, Jing; Shen, Qi; He, Zhanlong; Q, Ye; Li, Qihan

doi:10.1186/s12865-018-0240-5

Cited by 3 publications

(2 citation statements)

References 71 publications

(66 reference statements)

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“…CITT is also one of the primary conjugate vaccine carriers for polysaccharide antigens, including Haemophilus influenzae type b capsular antigen and the serogroup polysaccharides ( 16 – 19 ). Polysaccharide antigens require a protein conjugate to effectively elicit a T-cell-dependent immune response ( 20 , 21 ). To expand the use of conjugate vaccine applications, other platforms are being developed, including the recombinant diphtheria toxin derivative CRM-197 ( 22 – 24 ).…”

Section: Introductionmentioning

confidence: 99%

A Novel High-Potency Tetanus Vaccine

Przedpelski

Tepp

Pellett

et al. 2020

mBio

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Chemically inactivated tetanus toxoid (CITT) is clinically effective and widely used. However, CITT is a crude nonmalleable vaccine that contains hundreds of Clostridium tetani proteins, and the active component is present in variable and sometimes minor percentages of vaccine mass. Recombinant production of a genetically inactivated tetanus vaccine offers an opportunity to replace and improve the current tetanus vaccine. Previous studies showed the feasibility of engineering full-length tetanus toxin (TT) in Escherichia coli. In the present study, full-length TT was engineered with eight individual amino acid mutations (8MTT) to inactivate catalysis, translocation, and host receptor-binding functions, retaining 99.4% amino acid identity to native tetanus toxin. 8MTT purified as a 150-kDa single-chain protein, which trypsin nicked to a 100-kDa heavy chain and 50-kDa light chain. The 8MTT was not toxic for outbred mice and was >50 million-fold less toxic than native TT. Relative to CITT, 8MTT vaccination elicited a strong immune response and showed good vaccine potency against TT challenge. The strength of the immune response to both vaccines varied among individual outbred mice. These data support 8MTT as a candidate vaccine against tetanus and a malleable candidate conjugate vaccine platform to enhance the immune response to polysaccharides and other macromolecular molecules to facilitate a rapid response to emerging microbial pathogens. IMPORTANCE Chemical inactivation is a clinically effective mechanism to detoxify protein toxins to produce vaccines against microbial infections and to serve as a platform for production of conjugate polysaccharide vaccines. This method is widely used for the production of protein toxin vaccines, including tetanus toxoid. However, chemical modification alters the protein structure with unknown effects on antigenicity. Here, a recombinant full-length tetanus toxin (TT) is engineered with 8 mutations (8MTT) that inactivate three toxin functions: catalysis, translocation, and receptor binding. 8MTT is nontoxic and elicits a potent immune response in outbred mice. 8MTT also represents a malleable platform for the production of conjugate vaccines, which can facilitate a rapid vaccine response against emerging microbial pathogens.

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Section: Introductionmentioning

confidence: 99%

A Novel High-Potency Tetanus Vaccine

Przedpelski

Tepp

Pellett

et al. 2020

mBio

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“…Vaccines include live-attenuated and non-live composite ones ( Supplementary Table S4 ). There is no evidence of cell death associated with rotavirus vaccine (a live attenuated vaccine) or non-live Hib conjugate vaccine containing no aluminum adjuvant [ 48 ]. BCG vaccine induces the local cell death (apoptosis) of macrophages; however, BCG substrain Tokyo must have the minimum effect since it is considered the safest BCG vaccine [ 49 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

Kawasaki Disease and Vaccination: Prospective Case-Control and Case-Crossover Studies among Infants in Japan

et al. 2021

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The causal effects of vaccines on Kawasaki disease (KD) remain elusive. We aimed to examine the association between vaccines administered during infancy and the development of KD in Japan. We conducted a multicenter prospective case-control study using questionnaires and compared the vaccination status of infants (age: 6 weeks to 9 months) who developed KD (KD group; n = 102) and those who did not develop KD (non-KD group; n = 139). Next, we performed a case-crossover study of 98 cases in the KD group and compared the status of vaccinations between the case and control periods. We also compared the incidence of KD in children for each 5-year period before and after the addition of new vaccines (2012–2013) using data from the Nationwide Survey of KD. In the case-control study, the vaccination status of the KD and control groups did not differ to a statistically significant extent. Multivariable analysis of the vaccination status and patient backgrounds showed no significant association between vaccination and KD development. In the case-crossover study, the status of vaccinations during the case and control periods did not differ to a statistically significant extent. In the analysis of data from the Nationwide Survey of KD, the incidence of KD in children of ages subject to frequent vaccination showed no significant increases in the latter five years, 2014–2018. Based on these prospective analyses, we confirmed that vaccination in early infancy did not affect the risk of KD.

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Elicitation of integrated immunity in mice by a novel pneumococcal polysaccharide vaccine conjugated with HBV surface antigen

Wen

Huang²,

Chen³

et al. 2020

Sci Rep

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Pneumonia type 33 F capsular polysaccharide (Pn33Fps). The Streptococcus pneumoniae 33F strain (CMCC, National Center for Medical Culture Collection, Beijing, China) was cultured in tryptic soy broth (TSB; containing 15 g of tryptic soy broth, 5 g of soybean peptone, and 5 g of NaCl per liter) medium at 37 °C for 24 hours. The supernatant containing capsular polysaccharide was harvested through centrifugal fermentation (8000 rpm, 15 minutes). The polysaccharide was purified by 20% (V/V) ethanol precipitation (30 minutes, 2-8 °C) followed by ultrafiltration (50 KD, 30 minutes, 2-8 °C) to remove bacterial nucleic acids and proteins. Finally, capsular polysaccharides (Pn33Fps) were purified by Sepharose 4FF (GE, USA) 28. Conjugated vaccine (Pn33Fps_HBs). Pn33Fps were activated by incubation with cyanogen bromide (5 mg/mL; Fluke, USA) at 2-8 °C for 20 minutes. Adipic hydrazide solution (pH 8.0 ± 0.5; Sigma, USA) was then added to an equal volume of the abovementioned solution and incubated at 2-8 °C for 30 minutes. The residual cyanogen bromide was removed by ultrafiltration (0.25 MPa, 30 minutes) to obtain the polysaccharide derivatives, and the resulting polysaccharide derivatives were mixed with HBsAg at 1:0.5 (V:V). DEPC-carbodiimide (EDAC) was then added, and the mixture was incubated at 2-8 °C for 2-4 hours. This solution was purified by column chromatography to obtain a conjugated solution (Pn33Fps_HBs). Ethics. The experiments using mice (Charles River Laboratories Co., Ltd., Beijing, China) were designed based

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RNA gene profile variation in peripheral blood mononuclear cells from rhesus macaques immunized with Hib conjugate vaccine, Hib capsular polysaccharide and TT carrier protein

Cited by 3 publications

References 71 publications

A Novel High-Potency Tetanus Vaccine

A Novel High-Potency Tetanus Vaccine

Kawasaki Disease and Vaccination: Prospective Case-Control and Case-Crossover Studies among Infants in Japan

Elicitation of integrated immunity in mice by a novel pneumococcal polysaccharide vaccine conjugated with HBV surface antigen

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