Special Issue "Vaccine Vector"

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A special issue of Vaccines (ISSN 2076-393X).

Deadline for manuscript submissions: closed (31 May 2014)

Special Issue Editor

Guest Editor
Dr. Michael Barry (Website)

Mayo Clinic, Rochester, MN 55902, USA
Interests: gene therapy; gene-based vaccines; anti-cancer viruses

Special Issue Information

Dear Colleagues,

This issue is directed towards the state of art in using gene-based vaccines against infectious diseases and in other applications. Particular focus will be on more recent developments of viral and non-viral vectors, alternate methods of vaccination, and the impact of systemic and mucosal immunization for effective vaccination.

Dr. Michael Barry
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed Open Access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 300 CHF (Swiss Francs). English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.

Keywords

  • gene-based vaccines
  • viral vectors
  • non-viral vectors
  • gene gun
  • electroporation
  • replicating vectors
  • non-replicating vectors

Published Papers (7 papers)

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Research

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Open AccessArticle Enhancement of Mucosal Immunogenicity of Viral Vectored Vaccines by the NKT Cell Agonist Alpha-Galactosylceramide as Adjuvant
Vaccines 2014, 2(4), 686-706; doi:10.3390/vaccines2040686
Received: 23 May 2014 / Revised: 19 August 2014 / Accepted: 12 September 2014 / Published: 10 October 2014
Cited by 2 | PDF Full-text (641 KB) | HTML Full-text | XML Full-text
Abstract
Gene-based vaccination strategies, specifically viral vectors encoding vaccine immunogens are effective at priming strong immune responses. Mucosal routes offer practical advantages for vaccination by ease of needle-free administration, and immunogen delivery at readily accessible oral/nasal sites to efficiently induce immunity at distant [...] Read more.
Gene-based vaccination strategies, specifically viral vectors encoding vaccine immunogens are effective at priming strong immune responses. Mucosal routes offer practical advantages for vaccination by ease of needle-free administration, and immunogen delivery at readily accessible oral/nasal sites to efficiently induce immunity at distant gut and genital tissues. However, since mucosal tissues are inherently tolerant for induction of immune responses, incorporation of adjuvants for optimal mucosal vaccination strategies is important. We report here the effectiveness of alpha-galactosylceramide (α-GalCer), a synthetic glycolipid agonist of natural killer T (NKT) cells, as an adjuvant for enhancing immunogenicity of vaccine antigens delivered using viral vectors by mucosal routes in murine and nonhuman primate models. Significant improvement in adaptive immune responses in systemic and mucosal tissues was observed by including α-GalCer adjuvant for intranasal immunization of mice with vesicular stomatitis virus vector encoding the model antigen ovalbumin and adenoviral vectors expressing HIV env and Gag antigens. Activation of NKT cells in systemic and mucosal tissues along with significant increases in adaptive immune responses were observed in rhesus macaques immunized by intranasal and sublingual routes with protein or adenovirus vectored antigens when combined with α-GalCer adjuvant. These results support the utility of α-GalCer adjuvant for enhancing immunogenicity of mucosal vaccines delivered using viral vectors. Full article
(This article belongs to the Special Issue Vaccine Vector)
Open AccessArticle Gene Expression Driven by a Strong Viral Promoter in MVA Increases Vaccination Efficiency by Enhancing Antibody Responses and Unmasking CD8+ T Cell Epitopes
Vaccines 2014, 2(3), 581-600; doi:10.3390/vaccines2030581
Received: 31 March 2014 / Revised: 9 June 2014 / Accepted: 25 June 2014 / Published: 22 July 2014
Cited by 1 | PDF Full-text (1009 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Viral vectors are promising tools for vaccination strategies and immunotherapies. However, CD8+ T cell responses against pathogen-derived epitopes are usually limited to dominant epitopes and antibody responses to recombinant encoded antigens (Ags) are mostly weak. We have previously demonstrated that the [...] Read more.
Viral vectors are promising tools for vaccination strategies and immunotherapies. However, CD8+ T cell responses against pathogen-derived epitopes are usually limited to dominant epitopes and antibody responses to recombinant encoded antigens (Ags) are mostly weak. We have previously demonstrated that the timing of viral Ag expression in infected professional Ag-presenting cells strongly shapes the epitope immunodominance hierarchy. T cells recognizing determinants derived from late viral proteins have a clear disadvantage to proliferate during secondary responses. In this work we evaluate the effect of overexpressing the recombinant Ag using the modified vaccinia virus early/late promoter H5 (mPH5). Although the Ag-expression from the natural promoter 7.5 (P7.5) and the mPH5 seemed similar, detailed analysis showed that mPH5 not only induces higher expression levels than P7.5 during early phase of infection, but also Ag turnover is enhanced. The strong overexpression during the early phase leads to broader CD8 T cell responses, while preserving the priming efficiency of stable Ags. Moreover, the increase in Ag-secretion favors the induction of strong antibody responses. Our findings provide the rationale to develop new strategies for fine-tuning the responses elicited by recombinant modified vaccinia virus Ankara by using selected promoters to improve the performance of this viral vector. Full article
(This article belongs to the Special Issue Vaccine Vector)

Review

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Open AccessReview Emerging Vaccine Technologies
Vaccines 2015, 3(2), 429-447; doi:10.3390/vaccines3020429
Received: 24 December 2014 / Revised: 5 May 2015 / Accepted: 18 May 2015 / Published: 26 May 2015
Cited by 2 | PDF Full-text (319 KB) | HTML Full-text | XML Full-text
Abstract
Vaccination has proven to be an invaluable means of preventing infectious diseases by reducing both incidence of disease and mortality. However, vaccines have not been effectively developed for many diseases including HIV-1, hepatitis C virus (HCV), tuberculosis and malaria, among others. The [...] Read more.
Vaccination has proven to be an invaluable means of preventing infectious diseases by reducing both incidence of disease and mortality. However, vaccines have not been effectively developed for many diseases including HIV-1, hepatitis C virus (HCV), tuberculosis and malaria, among others. The emergence of new technologies with a growing understanding of host-pathogen interactions and immunity may lead to efficacious vaccines against pathogens, previously thought impossible. Full article
(This article belongs to the Special Issue Vaccine Vector)
Open AccessReview Vaccinia Virus LC16m8∆ as a Vaccine Vector for Clinical Applications
Vaccines 2014, 2(4), 755-771; doi:10.3390/vaccines2040755
Received: 3 June 2014 / Revised: 16 September 2014 / Accepted: 28 September 2014 / Published: 17 October 2014
PDF Full-text (441 KB) | HTML Full-text | XML Full-text
Abstract
The LC16m8 strain of vaccinia virus, the active ingredient in the Japanese smallpox vaccine, was derived from the Lister/Elstree strain. LC16m8 is replication-competent and has been administered to over 100,000 infants and 3,000 adults with no serious adverse reactions. Despite this outstanding [...] Read more.
The LC16m8 strain of vaccinia virus, the active ingredient in the Japanese smallpox vaccine, was derived from the Lister/Elstree strain. LC16m8 is replication-competent and has been administered to over 100,000 infants and 3,000 adults with no serious adverse reactions. Despite this outstanding safety profile, the occurrence of spontaneously-generated large plaque-forming virulent LC16m8 revertants following passage in cell culture is a major drawback. We identified the gene responsible for the reversion and deleted the gene (B5R) from LC16m8 to derive LC16m8Δ. LC16m8∆ is non-pathogenic in immunodeficient severe combined immunodeficiency (SCID) mice, genetically-stable and does not reverse to a large-plaque phenotype upon passage in cell culture, even under conditions in which most LC16m8 populations are replaced by revertants. Moreover, LC16m8∆ is >500-fold more effective than the non-replicating vaccinia virus (VV), Modified Vaccinia Ankara (MVA), at inducing murine immune responses against pathogenic VV. LC16m8∆, which expresses the SIV gag gene, also induced anti-Gag CD8+ T-cells more efficiently than MVA and another non-replicating VV, Dairen I minute-pock variants (DIs). Moreover, LC16m8∆ expressing HIV-1 Env in combination with a Sendai virus vector induced the production of anti-Env antibodies and CD8+ T-cells. Thus, the safety and efficacy of LC16m8∆ mean that it represents an outstanding platform for the development of human vaccine vectors. Full article
(This article belongs to the Special Issue Vaccine Vector)
Open AccessReview Self-Amplifying Replicon RNA Vaccine Delivery to Dendritic Cells by Synthetic Nanoparticles
Vaccines 2014, 2(4), 735-754; doi:10.3390/vaccines2040735
Received: 3 June 2014 / Revised: 29 August 2014 / Accepted: 28 September 2014 / Published: 16 October 2014
Cited by 3 | PDF Full-text (499 KB) | HTML Full-text | XML Full-text
Abstract
Dendritic cells (DC) play essential roles determining efficacy of vaccine delivery with respect to immune defence development and regulation. This renders DCs important targets for vaccine delivery, particularly RNA vaccines. While delivery of interfering RNA oligonucleotides to the appropriate intracellular sites for [...] Read more.
Dendritic cells (DC) play essential roles determining efficacy of vaccine delivery with respect to immune defence development and regulation. This renders DCs important targets for vaccine delivery, particularly RNA vaccines. While delivery of interfering RNA oligonucleotides to the appropriate intracellular sites for RNA-interference has proven successful, the methodologies are identical for RNA vaccines, which require delivery to RNA translation sites. Delivery of mRNA has benefitted from application of cationic entities; these offer value following endocytosis of RNA, when cationic or amphipathic properties can promote endocytic vesicle membrane perturbation to facilitate cytosolic translocation. The present review presents how such advances are being applied to the delivery of a new form of RNA vaccine, replicons (RepRNA) carrying inserted foreign genes of interest encoding vaccine antigens. Approaches have been developed for delivery to DCs, leading to the translation of the RepRNA and encoded vaccine antigens both in vitro and in vivo. Potential mechanisms favouring efficient delivery leading to translation are discussed with respect to the DC endocytic machinery, showing the importance of cytosolic translocation from acidifying endocytic structures. The review relates the DC endocytic pathways to immune response induction, and the potential advantages for these self-replicating RNA vaccines in the near future. Full article
(This article belongs to the Special Issue Vaccine Vector)
Figures

Open AccessReview DNA Virus Vectors for Vaccine Production in Plants: Spotlight on Geminiviruses
Vaccines 2014, 2(3), 642-653; doi:10.3390/vaccines2030642
Received: 5 June 2014 / Revised: 24 July 2014 / Accepted: 25 July 2014 / Published: 5 August 2014
Cited by 4 | PDF Full-text (408 KB) | HTML Full-text | XML Full-text
Abstract
Plants represent a safe, efficacious and inexpensive production platform by which to provide vaccines and other therapeutic proteins to the world’s poor. Plant virus expression vector technology has rapidly become one of the most popular methods to express pharmaceutical proteins in plants. [...] Read more.
Plants represent a safe, efficacious and inexpensive production platform by which to provide vaccines and other therapeutic proteins to the world’s poor. Plant virus expression vector technology has rapidly become one of the most popular methods to express pharmaceutical proteins in plants. This review discusses several of the state-of-the-art plant expression systems based upon geminiviruses that have been engineered for vaccine production. An overview of the advantages of these small, single-stranded DNA viruses is provided and comparisons are made with other virus expression systems. Advances in the design of several different geminivirus vectors are presented in this review, and examples of vaccines and other biologics generated from each are described. Full article
(This article belongs to the Special Issue Vaccine Vector)
Figures

Open AccessReview Developments in Viral Vector-Based Vaccines
Vaccines 2014, 2(3), 624-641; doi:10.3390/vaccines2030624
Received: 22 April 2014 / Revised: 18 June 2014 / Accepted: 30 June 2014 / Published: 29 July 2014
Cited by 15 | PDF Full-text (497 KB) | HTML Full-text | XML Full-text
Abstract
Viral vectors are promising tools for gene therapy and vaccines. Viral vector-based vaccines can enhance immunogenicity without an adjuvant and induce a robust cytotoxic T lymphocyte (CTL) response to eliminate virus-infected cells. During the last several decades, many types of viruses have [...] Read more.
Viral vectors are promising tools for gene therapy and vaccines. Viral vector-based vaccines can enhance immunogenicity without an adjuvant and induce a robust cytotoxic T lymphocyte (CTL) response to eliminate virus-infected cells. During the last several decades, many types of viruses have been developed as vaccine vectors. Each has unique features and parental virus-related risks. In addition, genetically altered vectors have been developed to improve efficacy and safety, reduce administration dose, and enable large-scale manufacturing. To date, both successful and unsuccessful results have been reported in clinical trials. These trials provide important information on factors such as toxicity, administration dose tolerated, and optimized vaccination strategy. This review highlights major viral vectors that are the best candidates for clinical use. Full article
(This article belongs to the Special Issue Vaccine Vector)

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