Immunogenicity and protective efficacy of DMT liposome-adjuvanted tuberculosis subunit CTT3H vaccine

Teng, Xiaochun; Tian, Man; Lǐ, Jiànróng; Tan, Songwei; Yuan, Xuefeng; Qi, Yu; Jing, Yukai; Zhang, Zhiping; Yue, Tingting; Zhou, Lei; Fan, Xionglin

doi:10.1080/21645515.2015.1037057

Cited by 15 publications

(24 citation statements)

References 61 publications

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“…We selected vaccine targets from this potential antigenic reservoir, based on the high recognition frequencies of T cells from LTBIs and ATBs. CTT3H was constructed based on low molecular-weight proteins like CFP-10 and TB10.4, which are the main species secreted by M. tuberculosis and presented in the early culture supernatant in vitro ( Teng et al, 2015 ). Currently, one-stage vaccine candidates, such as the fusion subunits Ag85B-ESAT-6 and Ag85B-TB10.4, are being evaluated in clinical trials ( Kaufmann, 2014 , Reither et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

“…Each dose of the vaccine containing 20 μg/100 μL of protein emulsified in 100 μL of the DMT adjuvant was prepared as previously described ( Teng et al, 2015 ). Specific-pathogen-free, 6-week-old, female C57BL/6 mice (Huafukang Biological Science, Beijing, China) were maintained in a Biosafety level 3 laboratory and fed standard laboratory chow.…”

Section: Methodsmentioning

confidence: 99%

“…A multistage fusion protein subunit, CMFO (Rv2875-Rv3044-Rv2073c-Rv0577), based on these four antigens was constructed. DMT was used as the adjuvant because of its ability as a strong inducer of Th1-type immunity ( Teng et al, 2015 ). The protective efficacy of DMT adjuvant and CMFO was compared with that of the subunits of single-stage CTT3H (CFP10-TB10.4-TB8.4-Rv3615c-HBHA) ( Teng et al, 2015 ) and two-stage A1D4 (Rv1813-Rv2660c-Ag85B-Rv2623-HspX) ( Wang et al, 2015 ) in immunized mice against primary infection, latent infection, and reactivation, respectively.…”

Section: Introductionmentioning

confidence: 99%

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A Multistage Subunit Vaccine Effectively Protects Mice Against Primary Progressive Tuberculosis, Latency and Reactivation

Teng

Wang

et al. 2017

EBioMedicine

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Adult tuberculosis (TB) is the main cause of TB epidemic and death. The infection results mainly by endogenous reactivation of latent TB infection and secondarily transmitted by exogenous infection. There is no vaccine for adult TB. To this end, we first chose antigens from a potential antigenic reservoir. The antigens strongly recognized T cells from latent and active TB infections that responded to antigens expressed by Mycobacterium tuberculosis cultured under different metabolic states. Fusions of single-stage polyprotein CTT3H, two-stage polyprotein A1D4, and multistage CMFO were constructed. C57BL/6 mice vaccinated with DMT adjuvant ed CMFO (CMFO-DMT) were protected more significantly than by CTT3H-DMT, and efficacy was similar to that of the only licensed vaccine, Bacillus Calmette–Guérin (BCG) and A1D4-DMT in the M. tuberculosis primary infection model. In the setting of BCG priming and latent TB infection, M. tuberculosis in the lung and spleen was eliminated more effectively in mice boosted with CMFO-DMT rather than with BCG, A1D4-DMT, or CTT3H-DMT. In particular, sterile immunity was only conferred by CMFO-DMT, which was associated with expedited homing of interferon-gamma+ CD4+ TEM and interleukin-2+ TCM cells from the spleen to the infected lung. CMFO-DMT represents a promising candidate to prevent the occurrence of adult TB through both prophylactic and therapeutic methods, and warrants assessment in preclinical and clinical trials.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Multistage Subunit Vaccine Effectively Protects Mice Against Primary Progressive Tuberculosis, Latency and Reactivation

Teng

Wang

et al. 2017

EBioMedicine

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“…Therefore, keeping in view the above findings, we chose CFA as adjuvant because of its wide spread use in the peptide immunization for increasing humoral and cellular immunity [ 85 – 87 ]. For peptide formulations in humans, the adjuvant like DMT-liposome can be highly useful, which is a cocktail of dimethyl di-octa-decyl ammonium bromide (DDA), monophosphoryl lipid-A (MPL) and trehalose dicoryno-mycolate (TDM) as it has been successfully tested for tuberculosis subunit vaccine [ 88 ]. We have also reported the cellular immune response in this study.…”

Section: Discussionmentioning

confidence: 99%

In silico analysis to identify vaccine candidates common to multiple serotypes of Shigella and evaluation of their immunogenicity

et al. 2017

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Shigellosis or bacillary dysentery is an important cause of diarrhea, with the majority of the cases occurring in developing countries. Considering the high disease burden, increasing antibiotic resistance, serotype-specific immunity and the post-infectious sequelae associated with shigellosis, there is a pressing need of an effective vaccine against multiple serotypes of the pathogen. In the present study, we used bio-informatics approach to identify antigens shared among multiple serotypes of Shigella spp. This approach led to the identification of many immunogenic peptides. The five most promising peptides based on MHC binding efficiency were a putative lipoprotein (EL PGI I), a putative heat shock protein (EL PGI II), Spa32 (EL PGI III), IcsB (EL PGI IV) and a hypothetical protein (EL PGI V). These peptides were synthesized and the immunogenicity was evaluated in BALB/c mice by ELISA and cytokine assays. The putative heat shock protein (HSP) and the hypothetical protein elicited good humoral response, whereas putative lipoprotein, Spa32 and IcsB elicited good T-cell response as revealed by increased IFN-γ and TNF-α cytokine levels. The patient sera from confirmed cases of shigellosis were also evaluated for the presence of peptide specific antibodies with significant IgG and IgA antibodies against the HSP and the hypothetical protein, bestowing them as potential future vaccine candidates. The antigens reported in this study are novel and have not been tested as vaccine candidates against Shigella. This study offers time and cost-effective way of identifying unprecedented immunogenic antigens to be used as potential vaccine candidates. Moreover, this approach should easily be extendable to find new potential vaccine candidates for other pathogenic bacteria.

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“…Modularization with surface attached antigens often elicit superior immune responses in comparison to encapsulated antigens perhaps owing to intracellular processing which is possible for the latter [67]. Despite this, encapsulation protects antigens from protease degradation, facilitates longer circulation time and can generate effective immune responses [68][69][70]. Low encapsulation efficiency is common due to antigen loss from the vesicle during the manufacturing process which involves film extrusion and high sheer methods [71].…”

Section: Antigenic Module Platform Base Modular Vaccinementioning

confidence: 99%

Platform technologies for modern vaccine manufacturing

Hume

Lua

2017

Vaccine

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Improved understanding of antigenic components and their interaction with the immune system, as supported by computational tools, permits a sophisticated approach to modern vaccine design. Vaccine platforms provide an effective tool by which strategically designed peptide and protein antigens are modularized to enhance their immunogenicity. These modular vaccine platforms can overcome issues faced by traditional vaccine manufacturing and have the potential to generate safe vaccines, rapidly and at a low cost. This review introduces two promising platforms based on virus-like particle and liposome, and discusses the methodologies and challenges.

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Immunogenicity and protective efficacy of DMT liposome-adjuvanted tuberculosis subunit CTT3H vaccine

Cited by 15 publications

References 61 publications

A Multistage Subunit Vaccine Effectively Protects Mice Against Primary Progressive Tuberculosis, Latency and Reactivation

A Multistage Subunit Vaccine Effectively Protects Mice Against Primary Progressive Tuberculosis, Latency and Reactivation

In silico analysis to identify vaccine candidates common to multiple serotypes of Shigella and evaluation of their immunogenicity

Platform technologies for modern vaccine manufacturing

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