DNA vaccines onward and upward! 20 years and counting! Highlights of the DNA Vaccines 2012 Meeting

Once again, from December 5 thru 7 of 2012 leading DNA vaccines researchers from around the world met at the beautiful Loews Coronado Bay Resort in San Diego, CA to present their latest research findings and exchange ideas on this vaccine strategy. The meeting, held under the auspices of the International Society of DNA Vaccines, highlighted the following theme: The 21st Century Vaccines Technology-Expanding Research Horizons and Pathways to Product Licensure. The meeting also celebrated the 20th anniversary of the first landmark and provocative presentations on DNA vaccines made at the 1992 Cold Spring Harbor Laboratory Annual Meeting on Vaccines. Since those initial reports 20 y ago, interest and enthusiasm in the DNA vaccine technology, including its clinical potential has waxed and waned. However, more recent interest in this vaccination strategy has resurged as evidenced by the large number of clinical trials evaluating its potential. As well, enthusiasm has increased due to interest in and positive results obtained with studies enhancing DNA vaccine efficacy through optimization strategies including the potentiation of delivery through various methods, including in vivo electroporation (EP).

We are excited to include in this volume 26 outstanding papers covering a wide range of interests and topics, including DNA vaccines against a number of infectious disease and cancers as well as papers describing methods to enhance the immune efficacy of the vaccines. As well, we are pleased to have the opportunity to publish these presentations in the outstanding journal Human Vaccines and Immunotherapeutics and thank the Editor-in-Chief, Dr Ronald Ellis, for the invitation.

From a historical standpoint two infectious agents targets that were initially evaluated with the DNA vaccine strategy, and presented at the seminal 1992 Cold Spring Harbor Vaccines Meeting, were influenza and the human immunodeficiency virus type 1 (HIV-1). As such, provocative research presentations, using naked DNA plasmid based vaccines were made at the 1992 meeting on influenza (Robinson group at University of Massachusetts and Liu group at Merck) and HIV-1 (Weiner group at University of Pennsylvania) targeting the nucleoprotein and envelope glycoprotein antigens respectively. To that end, it is fitting that among the excellent papers included in this monograph are reports on DNA vaccine strategies against influenza and HIV-1. In terms of targeting influenza, Kichaev et al.¹ of Inovio Pharmaceuticals presents a study using in vivo electroporation (EP) to deliver an influenza DNA vaccine to the mucosa. This work is summarized in their paper entitled “Electroporation mediated DNA vaccination directly to a mucosal surface results in improved immune responses.” Likewise, Almansour et.al.² presented a study examining cross sensitivity of serum antibody responses by DNA vaccines expressing hemagglutinin (HA) entitled “Cross reactivity of serum antibody responses elicited by DNA vaccines expression HA antigens from H1NI subtype influenza vaccines in the past 30 years.” As well on the influenza theme, Moise and colleagues³ presented a paper entitled “Immunization with cross-conserved H1N1 influenza CD4+ T cell epitopes lowers viral burden in HLA-DR3 transgenic mice. On the HIV front, Kulkarni presented 2 important papers on SIV DNA vaccines, one entitled “Vaccination with Vaxfectin^® adjuvanted SIV DNA induces long-lasting humoral immune responses able to reduce SIVmac251 Viremia”⁴ and the other titled “Comparison of intradermal and intramuscular delivery of followed by in vivo electroporation of SIV Env DNA macaques.”⁵ Wallace et al.⁶ presented a paper on how intracellular trafficking affects immunogenicity of a gag expressing DNA vaccine in “Post-translational intracellular trafficking determines the type of immune responses elicited by DNA vaccines expressing gag antigen of human immunodeficiency virus type-1 (HIV-1). As well, on an HIV-1 theme Nowroozalizadeh et al.⁷ presented a paper entitled “Short-term HIV-1 treatment interruption is associated with dysregulated TLR-stimuli responsiveness.” Rounding out the papers on an HIV target, Isaguliants and colleagues⁸ presented an important paper on the potential role of oxidative stress on efficacy of DNA vaccines entitled “Oxidative stress induces by HIV-1 reverse transcriptase modulates the enzyme’s performance on gene immunization.”

Papers on other viral vaccine targets included a presentation by Gil et. al.⁹ on human cytomegalovirus entitled “DNA vaccine prime followed by boost with live attenuated virus significantly improves antigen-specific T cell responses against human cytomegalovirus” as well as one by Wu et al.,¹⁰ targeting the hepatitis B virus entitled “Interleukin-22 as a molecular adjuvant facilitates IL-17 producing CD8⁺ T cell responses to HBV DNA vaccine in mice.” Several bacterial targets were also covered at the conference including a comprehensive review of the status of vaccines against tuberculosis, summarized in “The current state of tuberculosis vaccines,” authored by Hokey and Ginsberg.¹¹ As well, a paper targeting botulism toxin, authored by Burgain et al.¹² and entitled “DNA electroporation in rabbits as a method for generation of high-titer neutralizing antiserum,” was presented. Rounding out papers on bacterial pathogen targets was a study by Zhang and colleagues¹³ entitled “Potent monoclonal antibodies against Clostridium difficile toxin A elicited by DNA immunization,” which underscored the ability of the DNA vaccine technology to generate potentially efficacious monoclonal antibodies against bacterial, including this important cause of antibiotic induced diarrhea and gastroenteritis.

In terms of targeting parasitic infections, one presentation included in this volume targeted the important malarial parasite Plasmodium falciparum through vaccination against the circumsporozite protein utilizing a DNA prime: adenovirus boost strategy. This paper, authored by Tamminga and collaborators¹⁴ was entitled “Human adenovirus 5-vectored Plasmodium falciparum NMRC-MeV-Ad-PfCA vaccine encoding CSP and AMA1 is safe, well-tolerated and immunogenic but does not protect against controlled human malaria infection.”

Papers on non-infectious topics and targets dealt with cancer. Whittmore and Sykes¹⁵ presented a report entitled “A microarray method for identifying tumor antigens by screening a tumor cDNA expression library” which entailed the discovery of novel potential cancer antigens by screening an appropriate cancer related cDNA library. Ligtenberg et al.¹⁶ presented an important study on the potential role of transcription factors in eliciting antitumor cellular immune responses entitled “NF-κB activation during intradermal DNA vaccination is essential for eliciting tumor protective antigen-specific CTL responses.” Rounding out the cancer target papers was a study by Liu et al.¹⁷ documenting a DNA vaccine against a novel cell regulator of cancer growth. That paper is entitled “A DNA vaccine targeting p42.3 induces protective antitumor immunity via eliciting cytotoxic CD8⁺ T lymphocytes in a murine melanoma model.”

The last set of studies presented in this special issue are primarily methodology themed even though some of them utilize specific pathogens/antigens in their proof-of-concept analysis. Efficient strategies for the generation and manufacturing of DNA vaccines is one important requirement for the production of appropriate clinical grade material. To that end, two papers are presented on this topic. The first is authored by Reschner and colleagues¹⁸ entitled “Use of Staby technology for development and production of DNA vaccines free of antibiotic resistance gene.” The second paper, “Antibiotic-free production of a herpes simple virus 2 DNA vaccine in a high yield cGMP process” is presented by Nelson et. al.¹⁹ Coban and colleagues²⁰ then presents an interesting opinion/review paper on the potential influence of how DNA is “sensed” in the cell on the efficacy of the plasmid based vaccine entitled “DNA vaccine: A simple DNA sensing matter.” Rosli et. al.²¹ follows with a study on the important issue of delivery of mucosal DNA vaccines in a paper entitled “Mucosal genetic immunization through microsphere-based oral carriers.” As well, a paper on the use imaging technology to assess effective DNA vaccine delivery is presented by Petkov and their colleagues²² in their manuscript entitled “Evaluation of immunogen delivery by DNA immunization using non-invasive bioluminescence imaging.” A presentation on a more immunological mechanistic study follows, presented on the potential role of DC-SIGN as a receptor for DNA and protein and its effects on signaling pathways. Their paper, “DNA and protein co-administration induces tolerogenic dendritic cells through DC-SIGN mediated negative signals” was presented by Li et. al.²³

A clinical trial paper entitled “Tolerability of intramuscular and intradermal delivery by CELLECTRA adaptive constant electroporation device in healthy volunteers” was presented by Diehl and colleagues²⁴ at Inovio Pharmaceuticals and further documents the safety profile of the EP based DNA plasmid vaccine delivery strategy.

The penultimate manuscript presented in this special issue was a study entitled “Optimized and enhanced DNA plasmid vector based in vivo construction of a neutralizing anti-HIV-1 envelope glycoprotein Fab” authored by Muthumani and colleagues.²⁵ This paper documents an alternative method for generating and delivering passive antibody immunotherapy through the direct in vivo production of biologically active monoclonal antibody Fabs, through EP mediated delivery, of the Fab expressing DNA plasmids. As such, this strategy could have technical, logistical and practical advantages over conventional methods of delivery and/or generation of biologically active monoclonal antibodies. Finally, Kallen and colleagues²⁶ present an exciting paper entitled “A novel, disruptive vaccination technology: self-adjuvanted RNA based vaccines.” Importantly, this paper supports the idea that RNA based vaccines may have a significant potential in the nucleic acid vaccine arena.

In sum, we are pleased to present these 26 exciting papers which highlight presentations made at this meeting. Again, we are pleased to have the opportunity to have these studies published in this prestigious journal. We look forward to seeing everyone again at the 2014 meeting!

10.4161/hv.26628