Enhancing immune responses against SARS-CoV nucleocapsid DNA vaccine by co-inoculating interleukin-2 expressing vector in mice

Hu, Hui; Lei, Tao; Wang, Yabin; Chen, Liying; Yang, Jihong; Wang, Hanzhong

doi:10.1007/s10529-009-0061-y

Cited by 16 publications

(11 citation statements)

References 32 publications

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“…The N protein of human CoV is abundantly produced during infection and exhibits strong immunogenicity and conservancy, which can act as an ideal immunogen to elicit both cellular and humoral immune responses [50]. It is noteworthy that a large number of previous studies have shown the feasibility of the N protein as an immune target antigen or vaccine product [51][52][53][54][55][56][57][58][59][60]. Ma et al demonstrated that a SARS-CoV vaccine based on the N gene that was expressed by DNA plasmid and adenovirus vector could induce detectable antibody and IFN-γ [51].…”

Section: Discussionmentioning

confidence: 99%

“…Ma et al demonstrated that a SARS-CoV vaccine based on the N gene that was expressed by DNA plasmid and adenovirus vector could induce detectable antibody and IFN-γ [51]. Similar studies of the DNA vaccine based on the SARS-CoV N gene have shown potential inducing specific humoral and cellular immunity in BALB/c mice [52,53]. Moreover, multiple immunodominant B-cell epitopes, helper T-cell epitopes and CTL epitopes were mapped on the N protein of SARS-CoV [54][55][56][57][58].…”

Section: Discussionmentioning

confidence: 99%

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Epitope-Based Vaccine Target Screening against Highly Pathogenic MERS-CoV: An In Silico Approach Applied to Emerging Infectious Diseases

et al. 2015

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Middle East respiratory syndrome coronavirus (MERS-CoV) with pandemic potential is a major worldwide threat to public health. However, vaccine development for this pathogen lags behind as immunity associated with protection is currently largely unknown. In this study, an immunoinformatics-driven genome-wide screening strategy of vaccine targets was performed to thoroughly screen the vital and effective dominant immunogens against MERS-CoV. Conservancy and population coverage analysis of the epitopes were done by the Immune Epitope Database. The results showed that the nucleocapsid (N) protein of MERS-CoV might be a better protective immunogen with high conservancy and potential eliciting both neutralizing antibodies and T-cell responses compared with spike (S) protein. Further, the B-cell, helper T-cell and cytotoxic T lymphocyte (CTL) epitopes were screened and mapped to the N protein. A total of 15 linear and 10 conformal B-cell epitopes that may induce protective neutralizing antibodies were obtained. Additionally, a total of 71 peptides with 9-mer core sequence were identified as helper T-cell epitopes, and 34 peptides were identified as CTL epitopes. Based on the maximum HLA binding alleles, top 10 helper T-cell epitopes and CTL epitopes that may elicit protective cellular immune responses against MERS-CoV were selected as MERS vaccine candidates. Population coverage analysis showed that the putative helper T-cell epitopes and CTL epitopes could cover the vast majority of the population in 15 geographic regions considered where vaccine would be employed. The B- and T-cell stimulation potentials of the screened epitopes is to be further validated for their efficient use as vaccines against MERS-CoV. Collectively, this study provides novel vaccine target candidates and may prompt further development of vaccines against MERS-CoV and other emerging infectious diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Epitope-Based Vaccine Target Screening against Highly Pathogenic MERS-CoV: An In Silico Approach Applied to Emerging Infectious Diseases

et al. 2015

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“…vaccines, increased immune responses to hepatitis C core antigen [82], glycoprotein E2 of bovine diarrheal virus [83], and the S glycoprotein and nucleocapsid of SARS-coronavirus (SARS-CoV) [83,84]. Co-expression of IL-2 with genes encoding influenza A (H1N1 subtype) HA and neuraminidase in a bicistronic plasmid was more effective than coexpression of IL-12 or GM-CSF in protecting mice from lethal influenza infection [85].…”

Section: Il-2 Stimulates the Proliferation Of Both T And Nk Cells Andmentioning

confidence: 99%

Technologies for enhanced efficacy of DNA vaccines

Saade

Petrovsky

2012

Expert Review of Vaccines

272

225

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Despite many years of research, human DNA vaccines have yet to fulfill their early promise. Over the past 15 years, multiple generations of DNA vaccines have been developed and tested in preclinical models for prophylactic and therapeutic applications in the areas of infectious disease and cancer, but have failed in the clinic. Thus, while DNA vaccines have achieved successful licensure for veterinary applications, their poor immunogenicity in humans when compared with traditional protein-based vaccines has hindered their progress. Many strategies have been attempted to improve DNA vaccine potency including use of more efficient promoters and codon optimization, addition of traditional or genetic adjuvants, electroporation, intradermal delivery and various prime–boost strategies. This review summarizes these advances in DNA vaccine technologies and attempts to answer the question of when DNA vaccines might eventually be licensed for human use.

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“…Cytokine-encoding plasmids can be prepared along with the antigen-expressing plasmid and, local expression of cytokines at the injection site avoids the potential toxicity of systemically administered cytokines. Interleukin (IL)-2 induces the proliferation of T and NK cells, and has been extensively studied as a genetic adjuvant [73][74][75][76][77][78][79][80][81][82]. A fusion construct of Mycoplasma pneumoniae p1 gene carboxy terminal region with IL-2 resulted in enhanced vaccine responses in mice [83].…”

Section: Plasmid-encoded Cytokinesmentioning

confidence: 99%

Molecular mechanisms for enhanced DNA vaccine immunogenicity

Petrovsky

2015

Expert Review of Vaccines

262

252

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Summary In the two decades since their initial discovery, DNA vaccines technologies have come a long way. Unfortunately, when applied to human subjects inadequate immunogenicity is still the biggest challenge for practical DNA vaccine use. Many different strategies have been tested in preclinical models to address this problem, including novel plasmid vectors and codon optimization to enhance antigen expression, new gene transfection systems or electroporation to increase delivery efficiency, protein or live virus vector boosting regimens to maximise immune stimulation, and formulation of DNA vaccines with traditional or molecular adjuvants. Better understanding of the mechanisms of action of DNA vaccines has also enabled better use of the intrinsic host response to DNA to improve vaccine immunogenicity. This review summarizes recent advances in DNA vaccine technologies and related intracellular events and how these might impact on future directions of DNA vaccine development.

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Enhancing immune responses against SARS-CoV nucleocapsid DNA vaccine by co-inoculating interleukin-2 expressing vector in mice

Cited by 16 publications

References 32 publications

Epitope-Based Vaccine Target Screening against Highly Pathogenic MERS-CoV: An In Silico Approach Applied to Emerging Infectious Diseases

Epitope-Based Vaccine Target Screening against Highly Pathogenic MERS-CoV: An In Silico Approach Applied to Emerging Infectious Diseases

Technologies for enhanced efficacy of DNA vaccines

Molecular mechanisms for enhanced DNA vaccine immunogenicity

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