Expression and immunogenicity of Mycobacterium tuberculosis antigen 85 by DNA vaccination

Ulmer, Jeffrey B.; Liu, Margaret A.; Montgomery, Donna L.; Yawman, Anne M.; Deck, R. Randall; DeWitt, Corrille M.; Huygen, Kris

doi:10.1016/s0264-410x(96)00255-1

Cited by 59 publications

(30 citation statements)

References 11 publications

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“…This attenuation of BCG through laboratory passaging may have limited its clinical efficacy, making it necessary to optimize this vaccine. To this end, numerous groups attempted to either enhance the effectiveness of BCG or explore other vaccine strategies, such as plasmid DNA vaccination (11,14,15,22). With regard to DNA vaccination, while initial reports are promising, this approach has not proven to be more effective than BCG vaccination itself.…”

Section: Discussionmentioning

confidence: 99%

CpG Oligodeoxynucleotides and Interleukin-12 Improve the Efficacy ofMycobacterium bovisBCG Vaccination in Mice Challenged withM. tuberculosis

Freidag¹,

Melton²,

Collins³

et al. 2000

Infect Immun

103

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Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the only vaccine approved for prevention of tuberculosis. It has been postulated that serial passage of BCG over the years may have resulted in attenuation of its effectiveness. Because interleukin-12 (IL-12) and oligodeoxynucleotides (ODN) containing cytidine phosphate guanosine (CpG) motifs have been shown to enhance Th1 responses in vivo, they were chosen as adjuvants to increase the effectiveness of BCG vaccination. In this report, mice were vaccinated with BCG with or without IL-12 or CpG ODN and then challenged 6 weeks later via the aerosol route with the Erdman strain of M. tuberculosis. Mice vaccinated with BCG alone showed a 1-to 2-log reduction in bacterial load compared with control mice that did not receive any vaccination prior to M. tuberculosis challenge. Moreover, the bacterial loads of mice vaccinated with BCG plus IL-12 or CpG ODN were a further two-to fivefold lower than those of mice vaccinated with BCG alone. As an immune correlate, the antigen-specific production IFN-␥ and mRNA expression in spleen cells prior to challenge were evaluated. Mice vaccinated with BCG plus IL-12 or CpG ODN showed enhanced production of IFN-␥ compared with mice vaccinated with BCG alone. Finally, granulomas in BCG-vaccinated mice were smaller and more lymphocyte rich than those in unvaccinated mice; however, the addition of IL-12 or CpG ODN to BCG vaccination did not alter granuloma formation or result in added pulmonary damage. These observations support a role for immune adjuvants given with BCG vaccination to enhance its biologic efficacy.Mycobacterium tuberculosis infection is one of the most significant causes of mortality worldwide. Since the onset of the human immunodeficiency virus-AIDS epidemic, awareness of M. tuberculosis infection has resurfaced, as it is now a major cause of mortality for human immunodeficiency virus-infected individuals. Furthermore, the evolution of multidrug-resistant strains represents a significant health problem among normal, nonimmunocompromised individuals. The World Health Organization has recently declared the current situation to be a global emergency and has made it a priority to develop more effective vaccines against M. tuberculosis.The efficacy of M. bovis bacillus Calmette-Guérin (BCG) as a vaccine is dependent on many factors and determined clinically by its ability to prevent pulmonary or systemic disease following exposure to M. tuberculosis. Because the protective efficacy of BCG may range from 0 to 80% worldwide (18), it is necessary to determine the correlates of protection and exploit these issues in future vaccination attempts. For example, it was recently reported that the continued propagation of BCG over the past 60 years has lead to an evolution of BCG substrains marked by deletions in the parental M. bovis genome (1). Although the deletions do not include known bacterial virulence factors, the strain diversity may account for the attenuation or relative lack of efficacy against pulmonary disease. Ident...

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Section: Discussionmentioning

confidence: 99%

CpG Oligodeoxynucleotides and Interleukin-12 Improve the Efficacy ofMycobacterium bovisBCG Vaccination in Mice Challenged withM. tuberculosis

Freidag¹,

Melton²,

Collins³

et al. 2000

Infect Immun

103

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“…DNA vaccines use episomal vectors expressing antigens under eukaryotic promoters in the vaccinated host and therefore can elicit potent humoral and cellular immune responses comprising both CD4 and CD8 T cells (8,16). Several mycobacterial DNA vaccines have been shown to elicit protective immune responses in mice (7,10,21,23,31,35,(45)(46)(47)(48). However, considerable amounts of DNA are required, particularly in nonhuman primates and humans.…”

mentioning

confidence: 99%

Application of Mycobacterial Proteomics to Vaccine Design: Improved Protection by Mycobacterium bovis BCG Prime-Rv3407 DNA Boost Vaccination against Tuberculosis

Mollenkopf

Grode²,

Mattow

et al. 2004

Infect Immun

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Information from comparative proteome analysis of Mycobacterium tuberculosis and Mycobacterium bovis bacillus Calmette-Guérin (BCG) principally allows prediction of potential vaccine candidates. Thirty-six M. tuberculosis DNA vaccine candidates identified by comparative proteome analysis were evaluated in the mouse model for protection against low-dose aerosol M. tuberculosis infection. We identified the DNA vaccine candidate Rv3407 as a protective antigen and analyzed putative major histocompatibility complex class I epitopes by computational predictions and gamma interferon Elispot assays. Importantly, we discovered that the DNA vaccine Rv3407 improved the efficacy of BCG vaccination in a heterologous prime-boost vaccination protocol. Our data demonstrate the rationale of a combination of proteomics, epitope prediction, and broad screening of putative antigens for identification of novel DNA vaccine candidates. Furthermore, our experiments show that heterologous prime-boost vaccination with a defined antigen boost "on top" of a BCG primer provides superior protection against tuberculosis over vaccination with BCG alone.Together with AIDS and malaria, tuberculosis remains a major health threat, particularly in developing countries (50). Frequently, chemotherapy with at least three drugs over a period of several months is hampered by insufficient compliance, resulting in dramatically increasing incidences of multidrug-resistant strains of Mycobacterium tuberculosis (9). The currently available vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), is the most widely used viable vaccine worldwide (2,11,12,43). BCG apparently fails to protect against the most common form of the disease, pulmonary tuberculosis in adults, but it prevents miliary tuberculosis in newborns and toddlers (11,25). This raises two issues: first, novel tuberculosis vaccine candidates, which protect against adulthood tuberculosis, are urgently needed (25, 38); second, BCG vaccination of newborns should be continued and not be given up prematurely. A solution which fulfills both requirements can be offered by heterologous prime-boost vaccination strategies comprised of priming with BCG and boosting with a novel vaccine candidate (4, 14).In preclinical trials, genetic immunization with naked DNA has proven to be a powerful antigen discovery tool and vaccination protocol (8, 16). DNA vaccines use episomal vectors expressing antigens under eukaryotic promoters in the vaccinated host and therefore can elicit potent humoral and cellular immune responses comprising both CD4 and CD8 T cells (8,16). Several mycobacterial DNA vaccines have been shown to elicit protective immune responses in mice (7,10,21,23,31,35,(45)(46)(47)(48). However, considerable amounts of DNA are required, particularly in nonhuman primates and humans. In clinical trials, multiple high doses of DNA were required for the induction of immune responses (5, 27, 49).Elucidation of the complete genome of M. tuberculosis has provided a blueprint for the search for novel vaccine ...

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“…These include: (i) subunit vaccines consisting of mycobacterial preparations (32)(33)(34), culture filtrates (CF) or secreted molecules (35)(36)(37)(38)(39), proteins (40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53), lipoglycoproteins (54), and glycolipids (55-57); (ii) DNA vaccines (58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72); (iii) live, attenuated, nonpathogenic/auxotrophic or recombinant bacteria (73)(74)(75)(76)(77)(78)(79)(80)(81); and (iv) attenuated, nonmycobacterial vectors such as Salmonella or Vaccinia virus (77,…”

Section: Introductionmentioning

confidence: 99%

Vaccines Against Mycobacterium tuberculosis: An Overview from Preclinical Animal Studies to the Clinic

Coler¹,

Baldwin²,

Reed³

2012

Understanding Tuberculosis - Analyzing the Origin of Mycobacterium Tuberculosis Pathogenicity

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Expression and immunogenicity of Mycobacterium tuberculosis antigen 85 by DNA vaccination

Cited by 59 publications

References 11 publications

CpG Oligodeoxynucleotides and Interleukin-12 Improve the Efficacy ofMycobacterium bovisBCG Vaccination in Mice Challenged withM. tuberculosis

CpG Oligodeoxynucleotides and Interleukin-12 Improve the Efficacy ofMycobacterium bovisBCG Vaccination in Mice Challenged withM. tuberculosis

Application of Mycobacterial Proteomics to Vaccine Design: Improved Protection by Mycobacterium bovis BCG Prime-Rv3407 DNA Boost Vaccination against Tuberculosis

Vaccines Against Mycobacterium tuberculosis: An Overview from Preclinical Animal Studies to the Clinic

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