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DNA vaccines 2014 meeting: Highlights and overview a

Kenneth E. Ugen Guest Editors & David B. Weiner a

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University of South Florida Morsani College of Medicine; Tampa, FL USA

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University of Pennsylvania School of Medicine, Philadelphia, PA USA Accepted author version posted online: 09 Jul 2015.

Click for updates To cite this article: Kenneth E. Ugen Guest Editors & David B. Weiner (2015): DNA vaccines 2014 meeting: Highlights and overview, Human Vaccines & Immunotherapeutics, DOI: 10.1080/21645515.2015.1066947 To link to this article: http://dx.doi.org/10.1080/21645515.2015.1066947

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DNA vaccines 2014 meeting: Highlights and overview

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Guest Editors: Kenneth E. Ugen 1, and David B. Weiner2 1

University of South Florida Morsani College of Medicine; Tampa, FL USA 2 University of Pennsylvania School of Medicine, Philadelphia, PA USA

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As in prior DNA vaccine meetings prominent researchers in this field from throughout the world met in San Diego from July 21-23 at the Westin Gaslamp Quarter Hotel in the beautiful downtown area. The meeting once again was held under the auspices of the International Society of DNA Vaccines. The presentations highlighted the basic science as well as the applied aspects of nucleic acid vaccines and immunotherapies. In addition, exciting translational and clinical studies were also presented. We and the journal Human Vaccines and Immunotherapeutics (HVI), which is sponsoring this special issue highlighting the meeting, are very pleased to present 16 outstanding papers that encompass a wide range of topics and interests from the meeting. In this regard, on behalf of the society, we again thank Dr. Ronald Ellis, the editor-in-chief of HVI, for his invitation and other help to publish a special issue in this excellent journal. The work in this volume includes vaccine and immunotherapeutic studies targeting infectious diseases as well as malignancies. In addition, studies that examine methods to enhance the efficacy of DNA based immune intervention strategies, for the ultimate translation of these investigations to clinical trial evaluation and product approval and licensure is also presented. Importantly and appropriately papers are included from investigators from pharmaceutical/biotechnology companies as well as from academic institutions. One significant highlight of the meeting was the presentation by Inovio Pharmaceuticals of the results of a phase II randomized clinical trial using a DNA based HPV immunotherapy against cervical dysplasia, which indicated that the study met its primary and secondary endpoints. This provocative finding represents a significant advancement for the field and underscores the clinical utility of this vaccination/immunotherapeutic strategy. Papers in this special issue include a review article and several commentaries/min-reviews. The first review by Lee and colleagues entitled, “DNA vaccines, electroporation and their application in cancer research” summarizes the use of electroporation as a DNA delivery method, the strategies used to enhance immune responses, the cancer antigens tested as the escape mechanisms mounted by tumors1. All of these issues are presented in the review in the context of a focus on the progress of clinical trials using cancer DNA vaccines. The second paper is a commentary/mini-review by Pierce et. al. entitled “In-situ tumor vaccination: bringing the fight to the tumor” discusses the potential of this “local” therapy strategy which results in antigen release that drives antigen processing and presentation2. The commentary/mini-review entitled “Tuberculosis vaccine development: shifting focus amid increasing development challenges” by Graves and Hokey follows, which argues, based on recent failures in the testing of new tuberculosis vaccines, for a shift in emphasis from a product development strategy back to a research oriented approach3. The commentary/mini-review which follows, entitled “Opportunities for vaccine research in Europe” by Gancberg et. al., provides an excellent summary of the components of the European effort in vaccine research4. Finally, rounding out the group of reviews and commentaries is a paper 2

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entitled “Gene-based vaccines and immunotherapeutic strategies against neurodegenerative diseases: potential utility and limitations authored by Kudrna and Ugen which discusses the advantages, disadvantages and investigations, to date, of gene based immune interventions against this group of disorders, specifically targeting Alzheimer’s and Parkinson’s disease where specific antigens have been identified and targeted5. The subsequent two papers in the special issue are methodological in nature. The paper by Li and colleagues at the National Cancer Institute entitled “DNA is an efficient booster of dendritic cell-based vaccines” demonstrated that DC-based vaccine in combination with DNA in a heterologous DC prime: DNA boost strategy elicited polyfunctional T cells and robust antigen-specific central memory CD8+ T cells, suggesting that this method likely has considerable potential6. The other technique oriented paper, by Pirmoradi et. al. entitled “A microarray MEMS for biolistic delivery of vaccines and drug powders” demonstrates the ability of a microelectromechanical system (MEMS) to effectively deliver a broad range of particles formulated with either DNA for vaccination or with drugs 7 The following 8 research papers presented in this special issue utilize nucleic acid vaccine and immunotherapeutic strategies to target bacterial, viral and parasitic agents. The first 3 papers in this group target bacterial antigens. The study by Vijayachari and colleagues entitled “Immunogenicity of a novel enhanced consensus DNA vaccine encoding the leptospiral protein LipL-45” demonstrates the potential of an optimized consensus DNA vaccine against a lipoprotein antigen involved in infection by the causal agent of the serious bacterial zoonotic disease Leptospiriosis8. The study demonstrated the development of significant antibody and Th1 immune responses against the targeted antigen. Next Villareal and colleagues present a paper entitled “Alarmin IL-33 elicits potent TB-specific cell mediated responses”. In this study they report that co-administration of an interleukin-33 (IL-33) expressing plasmid was able to significantly enhance the generation of multifactorial CD4+ and CD8+ T cells against a DNA vaccine expressing a relevant Mycobacterium tuberculosis antigen9. This study underscores the utility of IL-33 as a vaccine adjuvant. In the next paper by Scott et. al. entitled “DNA vaccines targeting heavy chain C-terminal fragments of Clostridium botulism neurotoxin serotypes A,B and E induce potent humoral and cellular immunity and provide protection from lethal toxin challenge” the ability of an optimized DNA targeting the botulinum toxin and induce protective responses was demonstrated10 . Papers targeting viral antigens follow. The initial paper in this group by Scott and colleagues, entitled “Novel synthetic plasmid and DoggyboneTM DNA vaccines induce neutralizing antibodies and provide protection from lethal influenza challenge in mice”, demonstrated that a novel antigen expression cassette generating the influenza hemagglutinin antigen was able to induce potent antigen specific immune responses that were able to protect mice form lethal challenge with influenza11. Another paper targeting an influenza antigen is then presented. This paper by Borggren et. al. entitled “Vector optimization and needle-free intradermal application of a broadly protective polyvalent influenza A DNA vaccine for pigs and humans” demonstrated that delivery of an influenza antigen gene by a novel vector strategy coupled with a needle-free administration was able to stimulate antigen 3

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specific antibody responses to a level similar to those attained by electroporation mediated delivery12. The papers then shift to a study on the immune control of serious hemorrhagic filovirus infections, i.e. Ebola and Marburg virus. In the interesting study by Grant-Klein entitled “Codon-optimized filovirus DNA vaccines delivered by intramuscular electroporation protect cynomologous macaques from lethal Ebola and Marburg virus challenges” demonstrates considerable protection from infection by Ebola and Marburg virus challenge in monkeys which were vaccinated by electroporation mediated delivery, with plasmids expressing the glycoprotein antigens from these two filoviruses13. In the paper by Valentin et. al. entitled “Dose-dependent inhibition of gag cellular immunity by Env in SIV/HIV DNA vaccinated macaques” the investigators demonstrate that DNA vaccines mediating a balanced ratio of two critical HIV/SIV vaccine components, Gag and Env were important for overcoming immunological interference and resulted in the generation of maximal antigen specific antibody responses14. The final paper of the group targeting antigens form infectious agents is a study by Sedegah et.al. entitled “Controlled human malaria infection (CHMI) differentially affects cell-mediated and antibody responses to CSP and AMA1 induced by adenovirus with and without DNA priming”. In this study the investigators demonstrated important differences in cellular responses elicited by DNA-prime: adenovirus-5 boost compared to adenovirus-5 alone vaccines, both of which target relevant malarial antigens 15. The final paper in this special issue summarizes a cancer study. In this report entitled “MC32 tumor cells acquire Ag-specific CTL resistance through the loss of CEA in a colon cancer model” Lee and Sin demonstrated that MC32 (murine colon adenocarcinoma) cells likely were able to acquire resistance to CEA specific CTLs, generated by a DNA vaccine, through antigen loss16. This finding indicated that this process might have an overall general role in resistance of cancers to DNA as well as conventional immune based therapies. In sum, we are pleased to present these 16 excellent research papers and reviews, which capture some of the excitement and spirit of the presentations discussions at this meeting. As well, we are again excited to have the opportunity to publish a number of the studies in a special issue of the prestigious HVI journal. It has been an honor to work with all of you who contribute so much to the meeting and assisted with making the special issue a success. We look forward to seeing everyone again at the next DNA vaccines meeting!

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References 1. Lee S-H, Danishmalik SN, Sin J-I. DNA vaccines:electroporation and their applications in cancer treatment. Hum Vaccin Immunother 2015. 2. Pierce RH, Campbell JS, Pai SI, Brody JD, Kohrt HEK. In-situ tumor vaccination:bringing the fight to the tumor. Hum Vaccin Immunother 2015. 3. Graves A, J., Hokey DA. Tuberculosis vaccine development: shifting focus amid increasing development challenge. Hum Vaccin Immunother 2015. 4. Gancberg D, Hoeveler A, Martini A, Draghia-Akli R. Opportunities for vaccine research in europe. Hum Vaccin Immunother 2015. 5. Kudrna JJ, Ugen KE. Gene-based vaccines and immunotherapeutic strategies against neurodegenerative diseases: potential utility and limitations. Hum Vaccin Immunother 2015. 6. Li J, Valentin A, Beach RK, Alicea C, Felber BK, Pavlakis GN. DNA is an efficient booster of dendritic cell-based vaccine. Hum Vaccin Immunother 2015. 7. Pirmoradi FN, Pattekar AV, Linn F, Recht MI, Volkel AR, Wang Q, Anderson GB, Veiseh M, Kjono S, Peeters E, et al. A microarray MEMS device for biolistic delivery of vacine and drug powders. Hum Vaccin Immunother 2015. 8. Vijayachari P, Vedhagiri K, Mallilankaraman K, Mathus PP, Ugen KE, Sardesai NY, Weiner DB, Muthumani K. Immunogenicity of a novel enhances consensus DNA vaccine encoding the leptospiral protein LipL45. Hum Vaccin Immunother 2015. 9. Villareal DO, Siefert RJ, Weiner DB. Alarmin IL-33 elicits potent TB-specific cell mediated responses. Hum Vaccin Immunother 2015. 10. Scott VL, Villarreal DO, Hutnick NA, Walters JN, Ragwan E, Bdeir K, Yan J, Sardesai NY, Finnefrock AC, Weiner DB. DNA vaccines targeting heavy chain Cterminla frgaments of Clostridium botulinum neurotoxin serotypes A,B and E induce potent humoral and cellular immunity and provide protection from lethal toxin challenge. Hum Vaccin Immunother 2015. 11. Scott VL, Patel A, Villareal DO, Hensley SE, Ragwan E, Yan J, Sardesai NY, Rothwell PJ, Extance JP, Caproni LJ, et al. Novel synthetic plasmid and Doggybone DNA vaccines induce neutralizing antibodies and provide protection from lethal influenza challenge in mice. Hum Vaccin Immunother 2015. 12. Borggren M, Nielsen J, Bragstad K, Karlsson I, Krog JS, Williams JA, Fomsgaard A. Vector optimization and needle-free intradermal application of a broadly protective influenza A DNA vaccine for pigs and humans. Hum Vaccin Immunother 2015. 13. Grant-Klein RJ, Altamura LA, Badger CV, Bounds CE, Van Deusen NM, Kwilas SA, Vu HA, Warfield KL, Hooper JW, Hannaman D, et al. Codon-optimized filovirus DNA vaccines delivered by intramuscular electroporation protect cynomologus macaques from lethal Ebola and Marburg virus challenges. Hum Vaccin Immunother 2015. 14. Valentin A, Li J, Rosati M, Kulkarni V, Patel V, Jalah R, Alicca C, Reed S, Sardesai NY, Berkower I, et al. Dose-dependent inhibition of Gag cellualr immunity by Env in SIV/HIV DNA vaccinated macaques. Hum Vaccin Immunother 2015.

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15. Sedegah M, Hollingdale MR, Farooq F, Ganeshan H, Belmonte M, Huang J, Abot E, Limbach K, Chuang I, Tamminga C, et al. Controlled human malaria infection (CHMI) differentially affects cell-mediated and antibody responses to CSP and AMA1 induced by adenovirus vaccines with and without DNA-priming. Hum Vaccin Immunother 2015. 16. Lee SY, Sin JI. MC32 tumor cells acquire Ag-specifc CTL resistance through the loss of CEA in a colon cancer model. Hum Vaccin Immunother 2015.

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DNA vaccines 2014 meeting: Highlights and overview.

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