Nucleic acid vaccines: research tool or commercial reality.

Polynucleotide immunization has captured the imagination of numerous researchers and commercial companies around the world as a novel approach for inducing immunity in animals. Clearly, the 'proof-of-principle' has been demonstrated both in rodents and various animal species. However, to date, no commercial veterinary vaccine has been developed, or to our knowledge, is in the licensing phase. The present review summarizes the types of pathogens and host species for which polynucleotide immunization has been tried. We have tried to identify possible barriers to commercialization of this technology and areas that need attention if this promising technology is ever to become a reality in the commercial arena.

[1]  B. Murphy,et al.  Enhanced pulmonary histopathology induced by respiratory syncytial virus (RSV) challenge of formalin-inactivated RSV-immunized BALB/c mice is abrogated by depletion of interleukin-4 (IL-4) and IL-10 , 1994, Journal of virology.

[2]  H. Mohri,et al.  Induction of Systemic and Mucosal Immune Responses to Human Immunodeficiency Virus Type 1 by a DNA Vaccine Formulated with QS-21 Saponin Adjuvant via Intramuscular and Intranasal Routes , 1998, Journal of Virology.

[3]  G. Volckaert,et al.  Turkeys are protected from infection with Chlamydia psittaci by plasmid DNA vaccination against the major outer membrane protein , 1999, Clinical and experimental immunology.

[4]  R. Tigelaar,et al.  Intracutaneous vaccination of rabbits with the cottontail rabbit papillomavirus (CRPV) L1 gene protects against virus challenge . , 1997, Vaccine.

[5]  J. Berzofsky,et al.  Induction of cytotoxic T lymphocytes and antitumor immunity with DNA vaccines expressing single T cell epitopes. , 1996, Journal of immunology.

[6]  F. Chisari,et al.  DNA vaccination with plasmids encoding the intracellular (HBcAg) or secreted (HBeAg) form of the core protein of hepatitis B virus primes T cell responses to two overlapping Kb- and Kd-restricted epitopes. , 1997, International immunology.

[7]  L. Babiuk,et al.  Immunization of neonates with DNA encoding a bovine herpesvirus glycoprotein is effective in the presence of maternal antibodies. , 1999, Viral immunology.

[8]  M. Suckow,et al.  Biodegradable alginate microspheres as a delivery system for naked DNA. , 1999, Canadian journal of veterinary research = Revue canadienne de recherche veterinaire.

[9]  N. Christensen,et al.  Protection of Rabbits from Viral Challenge by Gene Gun-Based Intracutaneous Vaccination with a Combination of Cottontail Rabbit Papillomavirus E1, E2, E6, and E7 Genes , 1999, Journal of Virology.

[10]  L. Babiuk,et al.  Intradermal immunization with a bovine herpesvirus-1 DNA vaccine induces protective immunity in cattle. , 1998, The Journal of general virology.

[11]  V. Gerdts,et al.  Potency of an experimental DNA vaccine against Aujeszky's disease in pigs. , 1999, Veterinary microbiology.

[12]  D A Lauffenburger,et al.  Optimization of Cell Surface Binding Enhances Efficiency and Specificity of Molecular Conjugate Gene Delivery* , 1998, The Journal of Biological Chemistry.

[13]  W. Ballou,et al.  Immune responses induced by intramuscular or gene gun injection of protective deoxyribonucleic acid vaccines that express the circumsporozoite protein from Plasmodium berghei malaria parasites. , 1997, Journal of immunology.

[14]  R. Webster,et al.  Different T helper cell types and antibody isotypes generated by saline and gene gun DNA immunization. , 1997, Journal of immunology.

[15]  A. Rosenberg,et al.  Contribution of cells at the site of DNA vaccination to the generation of antigen-specific immunity and memory. , 1998, Journal of immunology.

[16]  E. Tulman,et al.  Immunogenicity of Vector DNA Vaccine Constructs of Pseudorabies Virus Immediate Early Gene (IE180) in Mice and Swine a , 1998, Annals of the New York Academy of Sciences.

[17]  T. Pugh,et al.  In vivo particle-mediated cytokine gene transfer into canine oral mucosa and epidermis. , 1996, Cancer gene therapy.

[18]  J. Clegg,et al.  Oral delivery of micro-encapsulated DNA vaccines. , 1998, Developments in biological standardization.

[19]  R. Webster,et al.  Protection against a lethal influenza virus challenge by immunization with a haemagglutinin-expressing plasmid DNA. , 1993, Vaccine.

[20]  V. Zurawski,et al.  Differential cellular and humoral immune responses to HCV core and HBV envelope proteins after genetic immunizations using chimeric constructs. , 1998, Vaccine.

[21]  P. Mason,et al.  Development of DNA vaccines for foot-and-mouth disease, evaluation of vaccines encoding replicating and non-replicating nucleic acids in swine. , 1999, Journal of biotechnology.

[22]  G. Keil,et al.  Immunization of cattle with a BHV1 vector vaccine or a DNA vaccine both coding for the G protein of BRSV. , 1997, Vaccine.

[23]  C R Howard,et al.  DNA is as effective as protein at inducing antibody in fish. , 1999, Vaccine.

[24]  G. Weiner,et al.  Immunostimulatory oligodeoxynucleotides containing the CpG motif are effective as immune adjuvants in tumor antigen immunization. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[25]  G. Rhodes,et al.  Self-replicating Semliki Forest virus RNA as recombinant vaccine. , 1994, Vaccine.

[26]  M. Chelbi-alix,et al.  Ability of insulin and DsRNA to induce interferon system and Hsp 70 in fibroblast and epithelial cells in relation to their effects on cell growth. , 1994, Experimental cell research.

[27]  L. Babiuk,et al.  Particle-mediated DNA immunization of cattle confers long-lasting immunity against bovine herpesvirus-1. , 1999, Virology.

[28]  G. Keil,et al.  Comparison of DNA application methods to reduce BRSV shedding in cattle. , 1998, Vaccine.

[29]  A. Lew,et al.  Targeting Improves the Efficacy of a DNA Vaccine against Corynebacterium pseudotuberculosis in Sheep , 1999, Infection and Immunity.

[30]  J. Ulmer,et al.  Priming of Cytotoxic T Lymphocytes by DNA Vaccines: Requirement for Professional Antigen Presenting Cells and Evidence for Antigen Transfer from Myocytes , 1997, Molecular medicine.

[31]  D. Tang,et al.  Genetic immunization is a simple method for eliciting an immune response , 1992, Nature.

[32]  R A Houghten,et al.  Immunogenicity. I. Use of peptide libraries to identify epitopes that activate clonotypic CD4+ T cells and induce T cell responses to native peptide ligands. , 1999, Journal of immunology.

[33]  J. Levy,et al.  Pathogenesis of human immunodeficiency virus infection. , 1993, Annals of the New York Academy of Sciences.

[34]  L. Babiuk,et al.  Altering the Cellular Location of an Antigen Expressed by a DNA-Based Vaccine Modulates the Immune Response , 1999, Journal of Virology.

[35]  H. Herweijer,et al.  A plasmid-based self-amplifying Sindbis virus vector. , 1995, Human gene therapy.

[36]  J. Mcghee,et al.  Mucosal immunization with DNA encoding influenza hemagglutinin. , 1997, Vaccine.

[37]  G. Volckaert,et al.  Protection of turkeys against Chlamydia psittaci challenge by gene gun-based DNA immunizations. , 1999, Vaccine.

[38]  N. Christensen,et al.  Intramuscular injection of plasmid DNA encoding cottontail rabbit papillomavirus E1, E2, E6 and E7 induces T cell-mediated but not humoral immune responses in rabbits. , 1999, Vaccine.

[39]  J. Northrop,et al.  Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[40]  S. Rosenberg,et al.  Cytokine enhancement of DNA immunization leads to effective treatment of established pulmonary metastases. , 1996, Journal of immunology.

[41]  Simon C Watkins,et al.  DNA–based immunization by in vivo transfection of dendritic cells , 1996, Nature Medicine.

[42]  H. Hauser,et al.  Polyvalent vaccination against hepatitis B surface and core antigen using a dicistronic expression plasmid. , 1998, Vaccine.

[43]  K. Heeg,et al.  Immunostimulatory DNA: Sequence‐dependent production of potentially harmful or useful cytokines , 1997, European journal of immunology.

[44]  C. Jallet,et al.  Immunization of dogs with a DNA vaccine induces protection against rabies virus. , 1999, Vaccine.

[45]  S. Chang,et al.  Sindbis virus DNA-based expression vectors: utility for in vitro and in vivo gene transfer , 1996, Journal of virology.

[46]  R. Germain,et al.  Predominant Role for Directly Transfected Dendritic Cells in Antigen Presentation to CD8+ T Cells after Gene Gun Immunization , 1998, The Journal of experimental medicine.

[47]  S. Hoffman,et al.  Strategy for development of a pre-erythrocytic Plasmodium falciparum DNA vaccine for human use. , 1997, Vaccine.

[48]  D. Hassett,et al.  Neonatal DNA immunization with a plasmid encoding an internal viral protein is effective in the presence of maternal antibodies and protects against subsequent viral challenge , 1997, Journal of virology.

[49]  L. Babiuk,et al.  Induction of immune responses to bovine herpesvirus type 1 gD in passively immune mice after immunization with a DNA-based vaccine. , 1999, The Journal of general virology.

[50]  S. Rosenberg,et al.  Developing recombinant and synthetic vaccines for the treatment of melanoma. , 1999, Current opinion in oncology.

[51]  V. Hinshaw,et al.  Immunization of Pigs with a Particle-Mediated DNA Vaccine to Influenza A Virus Protects against Challenge with Homologous Virus , 1998, Journal of Virology.

[52]  S. Johnston,et al.  Genetic to genomic vaccination. , 1997, Vaccine.

[53]  M. Eloit,et al.  Study of the delivery of the gD gene of pseudorabies virus to one-day-old piglets by adenovirus or plasmid DNA as ways to by-pass the inhibition of immune response by colostral antibodies. , 1997, Veterinary microbiology.

[54]  T. Banks,et al.  DNA Immunization against Herpes Simplex Virus: Enhanced Efficacy Using a Sindbis Virus-Based Vector , 1998, Journal of Virology.

[55]  G. Viljoen,et al.  Immune responses in a horse inoculated with the VP2 gene of African horsesickness virus. , 1999, The Onderstepoort journal of veterinary research.

[56]  E. Raz,et al.  Immunostimulatory DNA Sequences Necessary for Effective Intradermal Gene Immunization , 1996, Science.

[57]  C. Walker,et al.  Induction of cytotoxic T lymphocytes by intramuscular immunization with plasmid DNA is facilitated by bone marrow-derived cells. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[58]  James M. Wilson,et al.  Targeting genes: delivery and persistent expression of a foreign gene driven by mammalian regulatory elements in vivo. , 1989, The Journal of biological chemistry.

[59]  A. Krieg,et al.  The role of CpG dinucleotides in DNA vaccines. , 1998, Trends in microbiology.

[60]  Lars J. Brandén,et al.  A peptide nucleic acid–nuclear localization signal fusion that mediates nuclear transport of DNA , 1999, Nature Biotechnology.

[61]  A. Meyer,et al.  DNA vaccination using expression vectors carrying FIV structural genes induces immune response against feline immunodeficiency virus. , 1997, Vaccine.

[62]  I. Tubulekas,et al.  Alphavirus expression vectors and their use as recombinant vaccines: a minireview. , 1997, Gene.

[63]  A. Krieg,et al.  Lymphocyte activation by CpG dinucleotide motifs in prokaryotic DNA. , 1996, Trends in microbiology.

[64]  S. Beaucage,et al.  CpG motifs present in bacteria DNA rapidly induce lymphocytes to secrete interleukin 6, interleukin 12, and interferon gamma. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[65]  M. Heller,et al.  Can Patents Deter Innovation? The Anticommons in Biomedical Research , 1998, Science.

[66]  A. Iwasaki,et al.  Enhanced CTL responses mediated by plasmid DNA immunogens encoding costimulatory molecules and cytokines. , 1997, Journal of immunology.

[67]  P. Bretscher A strategy to improve the efficacy of vaccination against tuberculosis and leprosy. , 1992, Immunology today.

[68]  J. V. van Oirschot,et al.  Advances in the development and evaluation of bovine herpesvirus 1 vaccines. , 1996, Veterinary microbiology.

[69]  D. Miller,et al.  Protective Efficacy of DNA Vaccines against Duck Hepatitis B Virus Infection , 1998, Journal of Virology.

[70]  G. Acsadi,et al.  Direct gene transfer into mouse muscle in vivo. , 1990, Science.

[71]  J. Clegg,et al.  Poly(DL-lactide-co-glycolide)-encapsulated plasmid DNA elicits systemic and mucosal antibody responses to encoded protein after oral administration. , 1997, Vaccine.

[72]  R. Steinman,et al.  Granulocyte/macrophage colony-stimulating factor is essential for the viability and function of cultured murine epidermal Langerhans cells , 1987, The Journal of experimental medicine.

[73]  N. Templeton,et al.  New directions in liposome gene delivery , 1999, Molecular biotechnology.

[74]  D. Tang,et al.  DNA-based non-invasive vaccination onto the skin. , 1999, Vaccine.

[75]  J. Ulmer,et al.  Heterologous protection against influenza by injection of DNA encoding a viral protein. , 1993, Science.

[76]  B. Haagmans,et al.  Effect of vaccination route and composition of DNA vaccine on the induction of protective immunity against pseudorabies infection in pigs. , 1998, Veterinary immunology and immunopathology.

[77]  S. Hoffman,et al.  Induction of antigen-specific cytotoxic T lymphocytes in humans by a malaria DNA vaccine. , 1998, Science.

[78]  S. Levy,et al.  DNA vaccination with cytokine fusion constructs biases the immune response to ovalbumin. , 1997, Vaccine.

[79]  S. Johnston,et al.  Biological features of genetic immunization. , 1997, Vaccine.

[80]  L. Babiuk,et al.  Bovine herpesvirus 1: immune responses in mice and cattle injected with plasmid DNA , 1993, Journal of virology.

[81]  A. Krieg,et al.  CpG DNA is a potent enhancer of specific immunity in mice immunized with recombinant hepatitis B surface antigen. , 1998, Journal of immunology.

[82]  D. Putnam,et al.  PLGA microspheres containing plasmid DNA: preservation of supercoiled DNA via cryopreparation and carbohydrate stabilization. , 1999, Journal of pharmaceutical sciences.

[83]  I. Tubulekas,et al.  Alphaviruses as vectors for gene delivery. , 1996, Trends in biotechnology.

[84]  H. Herweijer,et al.  High expression of naked plasmid DNA in muscles of young rodents. , 1997, Human molecular genetics.

[85]  C. Tomlinson,et al.  Immunization of dogs and cats with a DNA vaccine against rabies virus. , 1999, Vaccine.

[86]  D. Onions,et al.  DNA Vaccination Affords Significant Protection against Feline Immunodeficiency Virus Infection without Inducing Detectable Antiviral Antibodies , 1998, Journal of Virology.

[87]  C. Turnes,et al.  DNA inoculation with a plasmid vector carrying the faeG adhesin gene of Escherichia coli K88ab induced immune responses in mice and pigs. , 1999, Vaccine.

[88]  Melvin Cohn,et al.  A Theory of Self-Nonself Discrimination , 1970, Science.

[89]  A. Krieg,et al.  Reduction of antigen expression from DNA vaccines by coadministered oligodeoxynucleotides. , 1998, Antisense & nucleic acid drug development.

[90]  B. Dixon The Third Vaccine Revolution , 1995, Bio/Technology.

[91]  J. Hopkins,et al.  Analysis of reporter gene expression in ovine dermis and afferent lymph dendritic cells in vitro and in vivo. , 1999, Veterinary immunology and immunopathology.

[92]  M. Eloit,et al.  Effective priming of neonates born to immune dams against the immunogenic pseudorabies virus glycoprotein gD by replication-incompetent adenovirus-mediated gene transfer at birth. , 1997, The Journal of general virology.

[93]  X. Mo,et al.  Recombinant polyepitope vaccines for the delivery of multiple CD8 cytotoxic T cell epitopes. , 1996, Journal of immunology.

[94]  D. Kerr,et al.  Serum and colostrum antibody responses induced by jet-injection of sheep with DNA encoding a Cryptosporidium parvum antigen. , 1995, Vaccine.

[95]  M. Eloit,et al.  Genetic immunization of seronegative one-day-old piglets against pseudorabies induces neutralizing antibodies but not protection and is ineffective in piglets from immune dams. , 1996, Veterinary research.

[96]  D. Love,et al.  DNA-mediated immunization with glycoprotein D of equine herpesvirus 1 (EHV-1) in a murine model of EHV-1 respiratory infection. , 1999, Vaccine.

[97]  C. Olsen,et al.  Antibody responses to DNA vaccination of horses using the influenza virus hemagglutinin gene. , 1999, Vaccine.

[98]  H. Robinson,et al.  Immunization of the Female Genital Tract with a DNA-Based Vaccine , 1998, Infection and Immunity.

[99]  W. Lin,et al.  Development of Th1 and Th2 populations and the nature of immune responses to hepatitis B virus DNA vaccines can be modulated by codelivery of various cytokine genes. , 1998, Journal of immunology.

[100]  L. J. Swango,et al.  Nucleic acid immunization protects dogs against challenge with virulent canine parvovirus. , 1998, Vaccine.

[101]  Y. Wu,et al.  Gene transfer facilitated by a cellular targeting molecule, reovirus protein σ1 , 2000, Gene Therapy.

[102]  R. Hoffman,et al.  Depth-targeted efficient gene delivery and expression in the skin by pulsed electric fields: an approach to gene therapy of skin aging and other diseases. , 1996, Biochemical and biophysical research communications.

[103]  B. Talbot,et al.  Vaccination of cattle with a DNA plasmid encoding the bovine viral diarrhoea virus major glycoprotein E2. , 1999, The Journal of general virology.

[104]  E. Sandström,et al.  Cellular cytotoxic response induced by DNA vaccination in HIV-1-infected patients , 1998, The Lancet.

[105]  J. Haynes,et al.  Manipulation of HIV-1 gp120-specific immune responses elicited via gene gun-based DNA immunization. , 1997, Vaccine.

[106]  B. Rouse,et al.  Induction of mucosal immunity against herpes simplex virus by plasmid DNA immunization , 1997, Journal of virology.

[107]  G. Schuler,et al.  Granulocyte/macrophage colony-stimulating factor and interleukin 1 mediate the maturation of murine epidermal Langerhans cells into potent immunostimulatory dendritic cells , 1988, The Journal of experimental medicine.

[108]  S. Dea,et al.  Immune response in pigs vaccinated with plasmid DNA encoding ORF5 of porcine reproductive and respiratory syndrome virus. , 1998, The Journal of general virology.

[109]  M. Sakaguchi,et al.  Protection of chickens from Newcastle disease by vaccination with a linear plasmid DNA expressing the F protein of Newcastle disease virus. , 1996, Vaccine.

[110]  H L Robinson,et al.  DNA vaccines: protective immunizations by parenteral, mucosal, and gene-gun inoculations. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[111]  T. Kimman,et al.  Vaccination of pigs against pseudorabies virus with plasmid DNA encoding glycoprotein D. , 1999, Vaccine.

[112]  J. Scheerlinck,et al.  Bm86 antigen induces a protective immune response against Boophilus microplus following DNA and protein vaccination in sheep. , 1999, Veterinary immunology and immunopathology.

[113]  T. Braciale,et al.  Induction of Th-1 and Th-2 Responses by Respiratory Syncytial Virus Attachment Glycoprotein Is Epitope and Major Histocompatibility Complex Independent , 1999, Journal of Virology.

[114]  M. Parrington,et al.  Protection against Respiratory Syncytial Virus Infection by DNA Immunization , 1998, The Journal of experimental medicine.

[115]  Mönkkönen,et al.  Lipid fusion in oligonucleotide and gene delivery with cationic lipids. , 1998, Advanced drug delivery reviews.

[116]  J. Waterkeyn,et al.  Sequential nucleic acid and recombinant adenovirus vaccination induces host‐protective immune responses against Taenia ovis infection in sheep , 1997, Parasite immunology.

[117]  V. Gerdts,et al.  Protection of pigs against Aujeszky's disease by DNA vaccination. , 1997, The Journal of general virology.

[118]  H. Bielefeldt-Ohmann,et al.  Establishment of stable, cell-mediated immunity that makes "susceptible" mice resistant to Leishmania major. , 1992, Science.

[119]  A. Moraillon,et al.  Enhancement of feline immunodeficiency virus (FIV) infection after DNA vaccination with the FIV envelope , 1997, Journal of virology.

[120]  S. Fahrenkrug,et al.  Genetic immunization of rainbow trout (Oncorhynchus mykiss) against infectious hematopoietic necrosis virus. , 1996, Molecular marine biology and biotechnology.

[121]  Russell,et al.  Mammalian granulocyte–macrophage colony‐stimulating factor and some CpG motifs have an effect on the immunogenicity of DNA and subunit vaccines in fish , 1999, Immunology.

[122]  C. L. Wright,et al.  The adjuvant effects of mycoviral dsRNA and polyinosinic:polycytidylic acid on the murine immune response. , 1985, Biochemical and biophysical research communications.

[123]  J. Neil,et al.  Factors influencing cellular immune responses to feline immunodeficiency virus induced by DNA vaccination. , 2000, Vaccine.

[124]  F. Osorio,et al.  Antibody and cellular immune responses of swine following immunisation with plasmid DNA encoding the PRRS virus ORF's 4, 5, 6 and 7. , 1999, Research in veterinary science.

[125]  T. Kipps,et al.  DNA vaccines encoding full-length or truncated Neu induce protective immunity against Neu-expressing mammary tumors. , 1998, Cancer research.

[126]  P. Mason,et al.  Plasmid DNA encoding replicating foot-and-mouth disease virus genomes induces antiviral immune responses in swine , 1997, Journal of virology.

[127]  A. Chalian,et al.  Engineering of in vivo immune responses to DNA immunization via codelivery of costimulatory molecule genes , 1997, Nature Biotechnology.

[128]  L. Kwak,et al.  Genetic fusion of chemokines to a self tumor antigen induces protective, T-cell dependent antitumor immunity , 1999, Nature Biotechnology.

[129]  A. Osterhaus,et al.  Induction of protective immunity to Theileria annulata using two major merozoite surface antigens presented by different delivery systems. , 1997, Vaccine.

[130]  R. Spier International meeting on the nucleic acid vaccines for the prevention of infectious disease and regulating nucleic acid (DNA) vaccines. Natcher Conference Center NIH, Bethesda, MD 5-8 February, 1996. , 1996, Vaccine.

[131]  K. Timmis,et al.  Oral Somatic Transgene Vaccination Using Attenuated S. typhimurium , 1997, Cell.

[132]  A. Iwasaki,et al.  The dominant role of bone marrow-derived cells in CTL induction following plasmid DNA immunization at different sites. , 1997, Journal of immunology.