A novel DNA vaccine for protective immunity against virulent Mycobacterium bovis in mice

Liu, Siguo; Gong, Qianhong; Wang, Chunlai; Liu, Huifang; Wang, Yong; Guo, Sheping; Wang, Weili; Liu, Jiandong; Shao, Meili; Chi, Lei; Zhao, Kun; Wang, Zhenguo; Shi, Yan-Li; Huang, Ying; GuLi, Aman; Zhang, Chunsheng; Kong, Xiangang

doi:10.1016/j.imlet.2008.01.008

Cited by 10 publications

(7 citation statements)

References 65 publications

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“…Hence, in addition to measuring systemic‐level IFN‐γ responses in the present study, we also sought to identify any vaccine‐mediated pulmonary protection induced by the DNA immunization by challenging mice via aerosol exposure to virulent M. bovis . Previous studies have indicated that DNA‐based vaccines in rodents have the potential to confer measurable protection against M. bovis 10 , 11 , 27 . In these studies, one major measure of protection was to observe a post‐challenge reduction in pathogen burdens among vaccinees; the same measurement was used here as the means of assessing any vaccine‐mediated protection against M. bovis .…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have indicated that DNA-based vaccines in rodents have the potential to confer measurable protection against M. bovis. 10,11,27 In these studies, one major measure of protection was to observe a postchallenge reduction in pathogen burdens among vaccinees; the same measurement was used here as the means of assessing any vaccinemediated protection against M. bovis. However, in the present study, the only vaccine treatment that conferred significant protection against pulmonary M. bovis challenge was BCG immunization, indicating that the DNA vaccination regime used here is not, on its own, a suitable alternative to the current TB vaccine.…”

Section: Discussionmentioning

confidence: 99%

“…Partly owing to this variable efficacy, and in part because of the ongoing safety concerns regarding the use of a live attenuated bacillus as an injectable vaccine, recent research objectives have focussed on the development of alternative sub‐unit TB vaccines 6 . DNA‐based vaccines, alone or in combination with recombinant vector or protein or peptide immunization, have been reported to provide protection against M. tuberculosis or M. bovis challenge in animal models 7 , 8 , 9 , 10 . However, although reports have shown the induction of strong mycobacterial antigen‐inducible interferon‐gamma (IFN‐γ) responses via DNA vaccination, 10 , 11 no sub‐unit vaccination regime has yet surpassed the protective efficacy conferred by BCG‐based immunization.…”

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confidence: 99%

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Immunogenicity and protective efficacy of mycobacterial DNA vaccines incorporating plasmid‐encoded cytokines against Mycobacterium bovis

et al. 2010

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DNA-based vaccines, alone or in combination with other sub-unit vaccination regimes, represent an alternative to live mycobacterial vaccines for protective immunization against tuberculosis. Here, we have used a murine immunization or Mycobacteriam bovis aerosol challenge model to assess the immunogenicity and protective efficacy of mycobacterial DNA vaccines. Mice that received immunization with DNA constructs encoding M. bovis antigen 85A (Ag85-A) and arget(ESAT-6) produced measurable interferon-gamma (IFN-c) responses to CD4 + T-cell epitope-peptide recall antigens in vitro. The magnitude of these responses was enhanced by co-delivery of a construct encoding murine cytokines (macrophage inhibitory protein (MIP)-1a or interleukin(IL)-7), although they did not the match responses observed in mice that received Bacille CalmetteÀGuerin(BCG) immunisation. In contrast, DNA priming followed by boosting with modified vaccinia Ankara (MVA) vaccine (expressing M. tuberculosis Ag85-A) invoked higher IFN-c levels, with the most immunogenic regime of Ag85 or ESAT or IL-7 prime followed by MVA boost being of commensurate immunogenicity to BCG. Despite this, neither DNA alone nor DNA-prime or MVA boost regimes conferred measurable protection against aerosol challenge with virulent M. bovis. These data highlight both the promise and the shortcomings of new generation subunit tuberculosis vaccines, with particular emphasis on their potential as vaccines against M. bovis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Immunogenicity and protective efficacy of mycobacterial DNA vaccines incorporating plasmid‐encoded cytokines against Mycobacterium bovis

et al. 2010

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“…67 DNA expressing a fusion of MPB64/Ag85B/ESAT6 was superior to a mixture of plasmids expressing the separate antigens and gave protection equivalent to BCG. 68 The protective effect of DNA expressing hsp65 against BCG challenge was enhanced by incorporating epitopes of ESAT6, Ag85A/B and CFP10 within the hsp65 backbone. 32 The protective effect of hsp65 DNA against H37Rv challenge was increased by expression as a fusion with hIL-2, but did not surpass that of BCG.…”

Section: Tb Prophylaxismentioning

confidence: 99%

Tuberculosis vaccine research in China

Lowrie

2012

Emerging Microbes & Infections

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It is now privately acknowledged that there may be little if any perceptible impact of the national Bacille Calmette–Guerin (BCG) vaccination program on disease prevalence, despite the extensive coverage of the newborn infant population and likely benefit in the early years of life. A better preventive vaccine than BCG is now being sought by Chinese researchers. Urgency has been added to the control problem by the emergence of multidrug-resistant tuberculosis (TB). Furthermore, expensive second-line drugs seem unlikely to be made available by the government to treat drug-resistant cases, so attention in addition has turned to the potential of immunotherapy as an adjunct to chemotherapy. Research trends are summarized here.

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“…Ayrıca uygulama ve saklama koşullarının daha güvenli olduğu, modifikasyon ve geliştirilme potansiyelinin de bulunduğu belirtilmektedir. 46 Xu ve ark. (44) pGJA-P/VAX olarak bilinen çürüğe karşı DNA aşısını geliştirmişlerdir.…”

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