Plasmid DNA vaccines capable of preventing viral, bacterial, and parasitic infections are currently under development. Our labs have shown that a plasmid DNA vaccine encoding the circumsporozoite protein of the malaria parasite elicits protective immunity against live sporozoite challenge in adult BALB/c mice. We now find that the same DNA vaccine induces tolerance rather than immunity when administered to 2-5 d-old mice. Neonatally tolerized animals were unable to mount antibody, cytokine or cytotoxic responses when rechallenged with DNA vaccine in vitro or in vivo. Tolerance was specific for immunogenic epitopes expressed by the vaccine-encoded, endogenously produced antigen. Mice challenged with exogenous circumsporozoite protein produced antibodies against a different set of epitopes, and were not tolerized. These findings demonstrate important differences in the nature and specificity of the immune response elicited by DNA vaccines versus conventional protein immunogens.
G Mor, G Yamshchikov, M Sedegah, M Takeno, R Wang, R A Houghten, S Hoffman, D M Klinman
Title and authors | Publication | Year |
---|---|---|
From genetic code to global health: the impact of nucleic acid vaccines on disease prevention and treatment
Del Bene A, D'Aniello A, Mottola S, Mazzarella V, Cutolo R, Campagna E, Benedetti R, Altucci L, Cosconati S, Di Maro S, Messere A |
RSC Medicinal Chemistry | 2025 |
Recent Advances in In Vivo Somatic Cell Gene Modification in Newborn Pups.
Nakamura S, Morohoshi K, Inada E, Sato Y, Watanabe S, Saitoh I, Sato M |
International journal of molecular sciences | 2023 |
Rabies Control and Treatment: From Prophylaxis to Strategies with Curative Potential
S Zhu, C Guo |
Viruses | 2016 |
Diabetes tolerogenic vaccines targeting antigen-specific inflammation
S Geng, H Zhang, X Zhou, Y He, X Zhang, X Xie, C Li, Z He, Q Yu, Y Zhong, DB Lowrie, G Zheng, B Wang |
Human Vaccines & Immunotherapeutics | 2015 |
An Overview of Challenges Limiting the Design of Protective Mucosal Vaccines for Finfish
HM Munangandu, S Mutoloki, Ø Evensen |
Frontiers in immunology | 2015 |
Variable effects of the co-administration of a GM-CSF-expressing plasmid on the immune response to flavivirus DNA vaccines in mice
H Chen, N Gao, J Wu, X Zheng, J Li, D Fan, J An |
Immunology Letters | 2014 |
Biolistic DNA Delivery
S Sudowe, AB Reske-Kunz |
2012 | |
Biolistic DNA Delivery
S Sudowe, AB Reske-Kunz |
2012 | |
Biolistic DNA Delivery
S Sudowe, AB Reske-Kunz |
2012 | |
Biolistic DNA Delivery
S Sudowe, AB Reske-Kunz |
2012 | |
Adjuvant-like Effect of Vaccinia Virus 14K Protein: A Case Study with Malaria Vaccine Based on the Circumsporozoite Protein
A Vijayan, CE Gomez, DA Espinosa, AG Goodman, L Sanchez-Sampedro, CO Sorzano, F Zavala, M Esteban |
2012 | |
Technologies for enhanced efficacy of DNA vaccines
F Saade, N Petrovsky |
Expert Review of Vaccines | 2012 |
Advances in Parasitology
H Huang |
Chagas Disease, Part A | 2011 |
FDA guidance on prophylactic DNA vaccines: analysis and recommendations
DM Klinman, S Klaschik, D Tross, H Shirota, F Steinhagen |
Vaccine | 2010 |
Methods in Microbiology
V Tchikov, J Fritsch, D Kabelitz, S Schütze |
Methods in Microbiology | 2010 |
Vaccines for Pandemic Influenza
RW Compans, WA Orenstein |
2009 | |
Vaccines for Pandemic Influenza
RW Compans, WA Orenstein |
2009 | |
Vaccines for Pandemic Influenza
RW Compans, WA Orenstein |
2009 | |
Vaccines for Pandemic Influenza
RW Compans, WA Orenstein |
2009 | |
Vaccines for Pandemic Influenza
RW Compans, WA Orenstein |
2009 | |
Vaccines for Pandemic Influenza
RW Compans, WA Orenstein |
2009 | |
Vaccines for Pandemic Influenza
RW Compans, WA Orenstein |
2009 | |
Vaccines for Pandemic Influenza
RW Compans, WA Orenstein |
2009 | |
Neonatal immunity: faulty T-helpers and the shortcomings of dendritic cells
H Zaghouani, CM Hoeman, B Adkins |
Trends in Immunology | 2009 |
Induction of immune responses and protection in mice against rabies using a self-replicating RNA vaccine encoding rabies virus glycoprotein
S Saxena, AA Sonwane, SS Dahiya, CL Patel, M Saini, A Rai, PK Gupta |
Veterinary Microbiology | 2009 |
Use of Vaxfectin Adjuvant with DNA Vaccine Encoding the Measles Virus Hemagglutinin and Fusion Proteins Protects Juvenile and Infant Rhesus Macaques against Measles Virus
CH Pan, GS Jimenez, N Nair, Q Wei, RJ Adams, FP Polack, A Rolland, A Vilalta, DE Griffin |
Clinical and vaccine immunology : CVI | 2008 |
Strategies for induction of protective immunity to bovine herpesvirus-1 in newborn calves with maternal antibodies
SD Hurk, M Snider, P Thompson, L Latimer, LA Babiuk |
Vaccine | 2008 |
A DNA vaccine candidate for B. anthracis immunization, pcDNA3.1+PA plasmid, induce Th1/Th2 mixed responses and protection in mice
F Vahedi, J Kyd, GM Jula, M Afzalaghaeei, M Kianizadeh, M Mahmoudi |
World Journal of Microbiology and Biotechnology | 2008 |
A sindbis virus replicon-based DNA vaccine encoding the rabies virus glycoprotein elicits immune responses and complete protection in mice from lethal challenge
S Saxena, SS Dahiya, AA Sonwane, CL Patel, M Saini, A Rai, PK Gupta |
Vaccine | 2008 |
DNA vaccination in aquaculture — Expert judgments of impacts on environment and fish health
F Gillund, R Dalmo, TC Tonheim, T Seternes, AI Myhr |
Aquaculture | 2008 |
What happens to the DNA vaccine in fish? A review of current knowledge
TC Tonheim, J Bøgwald, RA Dalmo |
Fish & Shellfish Immunology | 2008 |
Genetic vaccine for tuberculosis (pVAXhsp65) primes neonate mice for a strong immune response at the adult stage
AC Pelizon, DR Martins, SF Zorzella, AP Trombone, JC Lorenzi, RF Carvalho, IT Brandão, AA Coelho-Castelo, CL Silva, A Sartori |
Genetic vaccines and therapy | 2007 |
Perspectives in Medical Virology
KD Mena |
Perspectives in Medical Virology | 2007 |
ApoE gene delivery inhibits severe hypercholesterolemia in newborn ApoE-KO mice
E Signori, M Rinaldi, D Fioretti, S Iurescia, D Seripa, G Perrone, GD Norata, AL Catapano, VM Fazio |
Biochemical and Biophysical Research Communications | 2007 |
Genetic vaccination approaches against malaria based on the circumsporozoite protein
S Scheiblhofer, R Weiss, J Thalhamer |
Wiener klinische Wochenschrift | 2006 |
Live bacterial vaccines--a review and identification of potential hazards
A Detmer, J Glenting |
Microbial cell factories | 2006 |
Evaluation of the persistence and gene expression of an anti-Chlamydophila psittaci DNA vaccine in turkey muscle
K Loots, B Vleugels, E Ons, D Vanrompay, BM Goddeeris |
BMC veterinary research | 2006 |
DNA vaccines for poultry: the jump from theory to practice
L Haygreen, F Davison, P Kaiser |
Expert Review of Vaccines | 2005 |
An RNA vaccine based on recombinant Semliki Forest virus particles expressing the Cu,Zn superoxide dismutase protein of Brucella abortus induces protective immunity in BALB/c mice
AA Oñate, G Donoso, G Moraga-Cid, H Folch, S Céspedes, E Andrews |
Infection and immunity | 2005 |
Mucosal Immunology
WR Brown |
Mucosal Immunology | 2005 |
Cell Engineering
M Al-Rubeai, M Fussenegger |
2005 | |
DNA vaccine.
Cui Z |
Advances in genetics | 2005 |
Use of CpG oligodeoxynucleotides as immune adjuvants
DM Klinman, D Currie, I Gursel, D Verthelyi |
Immunological Reviews | 2004 |
Partial protection against infectious bursal disease virus through DNA-mediated vaccination with the VP2 capsid protein and chicken IL-2 genes
DJ Hulse, CH Romero |
Vaccine | 2004 |
DNA vaccination in utero: a new approach to induce protective immunity in the newborn
V Gerdts, C Tsang, PJ Griebel, LA Babiuk |
Vaccine | 2004 |
CpG DNA as a vaccine adjuvant
DM Klinman |
Expert Review of Vaccines | 2003 |
DNA vaccination
G Ada, I Ramshaw |
Expert Opinion on Emerging Drugs | 2003 |
Beneficial Autoimmunity to Proinflammatory Mediators Restrains the Consequences of Self-Destructive Immunity
G Wildbaum, MA Nahir, N Karin |
Immunity | 2003 |
A New Potent Route of DNA Vaccine Inoculation: DNA-Liposome Complexes on Bare Skin Induce Antigen-Special Antibody Responses
R Liang, F Zhuang, Z Meng, M Deng, C Zheng, M Duan |
Molecules (Basel, Switzerland) | 2003 |
Mucosally Delivered E1-Deleted Adenoviral Vaccine Carriers Induce Transgene Product-Specific Antibody Responses in Neonatal Mice
Z Xiang, Y Li, G Gao, JM Wilson, HC Ertl |
Journal of immunology (Baltimore, Md. : 1950) | 2003 |
Genetic immunization of neonates
A Bot, C Bona |
Microbes and Infection | 2002 |
Fate of Plasmid DNA Encoding Infectious Bursal Disease Virus VP2 Capsid Protein Gene After Injection into the Pectoralis Muscle of the Chicken
DJ Hulse, CH Romero |
Poultry science | 2002 |
Oral DNA Vaccination In Utero Induces Mucosal Immunity and Immune Memory in the Neonate
V Gerdts, M Snider, R Brownlie, LA Babiuk, PJ Griebel |
Journal of immunology (Baltimore, Md. : 1950) | 2002 |
Neonatal and early life vaccinology
CA Siegrist |
Vaccine | 2001 |
Semliki Forest virus-based vaccines: persistence, distribution and pathological analysis in two animal systems
MM Morris-Downes, KV Phenix, J Smyth, BJ Sheahan, S Lileqvist, DA Mooney, P Liljeström, D Todd, GJ Atkins |
Vaccine | 2001 |
A recombinant Semliki Forest virus particle vaccine encoding the prME and NS1 proteins of louping ill virus is effective in a sheep challenge model
MM Morris-Downes, BJ Sheahan, MN Fleeton, P Liljeström, HW Reid, GJ Atkins |
Vaccine | 2001 |
Induction of immunological memory in baboons primed with DNA vaccine as neonates
A Bot, M Shearer, S Bot, M Avriette, A Garcia-Sastre, G White, C Woods, R Kennedy, C Bona |
Vaccine | 2001 |
The regulation of DNA vaccines
HA Smith, DM Klinman |
Current Opinion in Biotechnology | 2001 |
Vaccination strategies for mucosal immune responses
PL Ogra, H Faden, RC Welliver |
Clinical microbiology reviews | 2001 |
Immunity to viral haemorrhagic septicaemia (VHS) following DNA vaccination of rainbow trout at an early life-stage
N Lorenzen, E Lorenzen, K Einer-Jensen |
Fish & Shellfish Immunology | 2001 |
Plasmid DNA Vaccines: Immunology, Tolerance, and Autoimmunity
G Mor, M Eliza |
Molecular Biotechnology | 2001 |
Cellular Immune Responses in Neonates
S Fadel, M Sarzotti |
International Reviews of Immunology | 2000 |
DNA Vaccination and the Immune Responsiveness of Neonates
A Bot |
International Reviews of Immunology | 2000 |
DNA Vaccines: Immunology, Application, and Optimization*
S Gurunathan, DM Klinman, RA Seder |
Annual Review of Immunology | 2000 |
Early life humoral response of ducks to DNA immunization against hepadnavirus large envelope protein
C Rollier, C Charollois, C Jamard, C Trepo, L Cova |
Vaccine | 2000 |
Differences in epitope recognition, isotype and titer of antisera to Plasmodium falciparum merozoite surface protein 4 raised by different modes of DNA or protein immunization
L Wang, JG Menting, CG Black, A Stowers, DC Kaslow, SL Hoffman, RL Coppel |
Vaccine | 2000 |
Development of Neonatal Th1/Th2 Function
B Adkins |
International Reviews of Immunology | 2000 |
Immune responses following neonatal DNA vaccination are long-lived, abundant, and qualitatively similar to those induced by conventional immunization
DE Hassett, J Zhang, M Slifka, JL Whitton |
Journal of virology | 2000 |
Fetal immunization by a DNA vaccine delivered into the oral cavity
V Gerdts, LA Babiuk, DL Hurk, PJ Griebel |
Nature Medicine | 2000 |
Naked DNA vaccination differentially modulates autoimmune responses in experimental autoimmune encephalomyelitis
K Selmaj, C Kowal, A Walczak, J Nowicka, CS Raine |
Journal of Neuroimmunology | 2000 |
Immunotherapy of Immune-Mediated Diabetes: Present and Future
N Maclaren |
Clinical Reviews in Allergy & Immunology | 2000 |
Prevention of neonatal tolerance by a plasmid encoding granulocyte-macrophage colony stimulating factor
KJ Ishii, WR Weiss, DM Klinman |
Vaccine | 1999 |
CpG motifs as immune adjuvants
DM Klinman, KM Barnhart, J Conover |
Vaccine | 1999 |
Immunization of Neonates with DNA Encoding a Bovine Herpesvirus Glycoprotein Is Effective in the Presence of Maternal Antibodies*
SV Hurk, R Braun, P Lewis, B Karvonen, L Babiuk, P Griebel |
Viral Immunology | 1999 |
Apoptosis of Murine Neonatal T Cells
B Adkins, M Nassiri |
International Reviews of Immunology | 1999 |
GENETIC VACCINES
JR Haynes |
Infectious Disease Clinics of North America | 1999 |
Studies on Antibody Responses Following Neonatal Immunization with Influenza Hemagglutinin DNA or Protein
TM Pertmer, HL Robinson |
Virology | 1999 |
Potential for plasmid DNAs as vaccines for the new millennium
KE Shroff, LR Smith, Y Baine, TJ Higgins |
Pharmaceutical Science & Technology Today | 1999 |
Propelling novel vaccines directed against tuberculosis through the regulatory process
MJ Brennan, FM Collins, SL Morris |
Tubercle and Lung Disease | 1999 |
Induction of immune responses to bovine herpesvirus type 1 gD in passively immune mice after immunization with a DNA-based vaccine
PJ Lewis, SD Hurk, LA Babiuk |
Journal of General Virology | 1999 |
Progress on Nucleic Acid-Based Vaccines for the Control of Human and Animal Diseases
TS Kanellos, AG Ambali, PH Russell |
OUTLOOK AGR | 1999 |
Immunogenicity of DNA Vaccines Expressing Tuberculosis Proteins Fused to Tissue Plasminogen Activator Signal Sequences
SH Kaufmann, Z Li, A Howard, C Kelley, G Delogu, F Collins, S Morris |
Infection and immunity | 1999 |
Optimization of vaccine responses in early life: The role of delivery systems and immunomodulators
J Kovarik, CA Siegrist |
Immunology and Cell Biology | 1998 |
DNA immunization of infants: potential and limitations
C Butts, I Zubkoff, DS Robbins, S Cao, M Sarzotti |
Vaccine | 1998 |
Enhancing immune responses using suicidal DNA vaccines
P Berglund, C Smerdou, MN Fleeton, Tubulekas, P Liljeström |
Nature Biotechnology | 1998 |
Plasmid DNA: A New Era in Vaccinology
G Mor |
Biochemical Pharmacology | 1998 |
Therapeutic Applications of CpG-Containing Oligodeoxynucleotides
DM Klinman |
Antisense and Nucleic Acid Drug Development | 1998 |
CpG DNA can induce strong Th1 humoral and cell-mediated immune responses against hepatitis B surface antigen in young mice
CL Millan, R Weeratna, AM Krieg, CA Siegrist, HL Davis |
Proceedings of the National Academy of Sciences | 1998 |
Medical Applications of Liposomes
T Daemen, AD Haan, A Arkema, J Wilschut |
Medical Applications of Liposomes | 1998 |
Gene vaccination: plasmid DNA is more than just a blueprint
H Tighe, M Corr, M Roman, E Raz |
Immunology Today | 1998 |
Gene Vaccination: Theory and Practice
E Raz |
1998 | |
Symposium in Immunology VII
MM Eibl, C Huber, HH Peter, U Wahn |
1998 | |
DNA immunization of neonates induces immunity despite the presence of maternal antibody
E Manickan, Z Yu, BT Rouse |
Journal of Clinical Investigation | 1997 |
DNA Vaccines
DL Montgomery, JB Ulmer, JJ Donnelly, MA Liu |
Pharmacology & Therapeutics | 1997 |
DNA immunization
AJ Ramsay, IA Ramshaw, GL Ada |
Immunology and Cell Biology | 1997 |
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
DE Hassett, J Zhang, JL Whitton |
Journal of virology | 1997 |
DNA immunization circumvents deficient induction of T helper type 1 and cytotoxic T lymphocyte responses in neonates and during early life
X Martinez, C Brandt, F Saddallah, C Tougne, C Barrios, F Wild, G Dougan, PH Lambert, CA Siegrist |
Proceedings of the National Academy of Sciences | 1997 |
Immunization with DNA vaccines in early life: Advantages and limitations as compared to conventional vaccines
CA Siegrist, PH Lambert |
Springer Seminars in Immunopathology | 1997 |
Genetic vaccines ? a revolution in vaccinology?
ZQ Xiang, S Pasquini, Z He, H Deng, Y Wang, MA Blaszczyk-Thurin, HC Ertl |
Springer Seminars in Immunopathology | 1997 |
Advances in Genetics
BH Bowman, F Yang, GS Adrian |
Advances in genetics | 1988 |
Advances in Virus Research
LA Babiuk, MJ Lawman, HB Ohmann |
Advances in virus research | 1988 |