DNA Immunization for Influenza Virus: Studies Using Hemagglutinin‐ and Nucleoprotein‐Expressing DNAs

Robinson, Harriet L.; Boyle, Christine Margaret; Feltquate, David; Morin, Merribeth J.; Santoro, Joseph C.; Webster, Robert G.

doi:10.1086/514176

Cited by 100 publications

(44 citation statements)

References 6 publications

(5 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…immunization with 100 g of DNA; doses delivered by i.m. at higher concentrations do not increase the immune response significantly beyond this level (27). Differences in the immune responses elicited by the DNA vaccines used in this study may be missed because of saturating immune responses induced by all four constructs at high dosage.…”

Section: Improved Humoral Responses With Pcag-ha-wpre Vaccinationsmentioning

confidence: 65%

“…Clearly, there is a need to enhance the potency of these vaccines. To amplify the immune response, DNA vaccine-primed animals must be boosted, whether it be by further DNA vaccinations (27) or by a live recombinant virus boost (28,34,35). Booster immunizations are required to raise immune responses to levels sufficient to protect against live pathogen challenge (as reviewed in Ref.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The Hybrid Cytomegalovirus Enhancer/Chicken β-Actin Promoter along with Woodchuck Hepatitis Virus Posttranscriptional Regulatory Element Enhances the Protective Efficacy of DNA Vaccines

Garg

Oran

Hon

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

DNA vaccines represent a novel and powerful alternative to conventional vaccine approaches. They are extremely stable and can be produced en masse at low cost; more importantly, DNA vaccines against emerging pathogens or bioterrorism threats can be quickly constructed based solely upon the pathogen’s genetic code. The main drawback of DNA vaccines is that they often induce lower immune responses than traditional vaccines, particularly in nonrodent species. Thus, improving the efficacy of DNA vaccines is a critical issue in vaccine development. In this study we have enhanced the efficacy of DNA vaccines by adopting strategies that increase gene expression. We generated influenza-hemagglutinin (HA)-encoding DNA vaccines that contain the hybrid CMV enhancer/chicken β-actin (CAG) promoter and/or the mRNA-stabilizing post-transcriptional regulatory element from the woodchuck hepatitis virus (WPRE). Mice were immunized with these DNA vaccines, and the influenza-HA-specific cellular and humoral immune responses were compared with a conventional, HA-encoding DNA vaccine whose gene expression was driven by the CMV immediate-early promoter (pCMV-HA). CAG promoter-driven DNA vaccines elicited significantly higher humoral and cellular immune responses compared with the pCMV-HA vaccine. DNA vaccines consisting of both CAG and WPRE elements (pCAG-HA-WPRE) induced the highest level of protective immunity, such that immunization with 10-fold lower DNA doses prevented death in 100% of the mice upon lethal viral challenge, whereas all mice immunized with the conventional pCMV-HA vaccine succumbed to influenza infection.

show abstract

Section: Improved Humoral Responses With Pcag-ha-wpre Vaccinationsmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

The Hybrid Cytomegalovirus Enhancer/Chicken β-Actin Promoter along with Woodchuck Hepatitis Virus Posttranscriptional Regulatory Element Enhances the Protective Efficacy of DNA Vaccines

Garg

Oran

Hon

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…AdV has been modified to express influenza A virus antigens; however, the recent failure of an AdV-based HIV vaccine candidate in a clinical trial has dampened enthusiasm for this viral vector (37). Recombinant DNA vaccines expressing influenza antigens have been tested in animal models and shown to induce protective antibody and T cell responses (38)(39)(40)(41). However, the need for repeated administration of DNA can be a hurdle for using the DNA-based vaccine for rapidly spreading influenza virus infection or general immunization compliance (i.e., ensuring individuals receive the full vaccination schedule).…”

Section: Discussionmentioning

confidence: 99%

Recombinant Parainfluenza Virus 5 Expressing Hemagglutinin of Influenza A Virus H5N1 Protected Mice against Lethal Highly Pathogenic Avian Influenza Virus H5N1 Challenge

Mooney

Gabbard

et al. 2013

J Virol

View full text Add to dashboard Cite

A safe and effective vaccine is the best way to prevent large-scale highly pathogenic avian influenza virus (HPAI) H5N1 outbreaks in the human population. The current FDA-approved H5N1 vaccine has serious limitations. A more efficacious H5N1 vaccine is urgently needed. Parainfluenza virus 5 (PIV5), a paramyxovirus, is not known to cause any illness in humans. PIV5 is an attractive vaccine vector. In our studies, a single dose of a live recombinant PIV5 expressing a hemagglutinin (HA) gene of H5N1 (rPIV5-H5) from the H5N1 subtype provided sterilizing immunity against lethal doses of HPAI H5N1 infection in mice. Furthermore, we have examined the effect of insertion of H5N1 HA at different locations within the PIV5 genome on the efficacy of a PIV5-based vaccine. Interestingly, insertion of H5N1 HA between the leader sequence, the de facto promoter of PIV5, and the first viral gene, nucleoprotein (NP), did not lead to a viable virus. Insertion of H5N1 HA between NP and the next gene, V/phosphorprotein (V/P), led to a virus that was defective in growth. We have found that insertion of H5N1 HA at the junction between the small hydrophobic (SH) gene and the hemagglutinin-neuraminidase (HN) gene gave the best immunity against HPAI H5N1 challenge: a dose as low as 1,000 PFU was sufficient to protect against lethal HPAI H5N1 challenge in mice. The work suggests that recombinant PIV5 expressing H5N1 HA has great potential as an HPAI H5N1 vaccine.

show abstract

“…1). Influenza virus A/PR/8/34 (H1N1) HA and NP were amplified from pJW4303/H1 (30) and pCMV/NP (27). Murine IRF-1 was obtained from pCDM8/mIRF-1 provided by T. Taniguchi (University of Tokyo, Tokyo, Japan).…”

Section: Methodsmentioning

confidence: 99%

Regulation of DNA-Raised Immune Responses by Cotransfected Interferon Regulatory Factors

Sasaki

Amara

Yeow

et al. 2002

J Virol

Self Cite

View full text Add to dashboard Cite

type 2 were stronger for immunizations with IRF-3 as an adjuvant than for immunizations with IRF-7 as an adjuvant. Moderate adjuvant effects for antibody were observed. The isotypes of the antibody responses reflected the method of DNA delivery; intramuscular deliveries of DNA predominantly raised immunoglobulin G2a (IgG2a), whereas gene gun deliveries of DNA predominantly raised IgG1. These biases were enhanced by the codelivered IRFs. Overall, under the conditions of our experiments, IRF-3 had good activity for T cells, IRF-7 had good activity for both antibody and T cells, and IRF-1 had good activity for antibody.A central challenge for DNA-based immunization is producing sufficient antigen (Ag) and the correct inflammatory signals to achieve strong immune responses. DNA-based immunizations are like viral infections in producing immunizing proteins within the cells of the host. Unmethylated CpG motifs in plasmids provide adjuvant activity for the expressed Ags by stimulating the Toll 9 receptor (11). Codelivered genes for lymphokines, chemokines, and costimulatory molecules can provide additional adjuvant activity for DNA vaccines (for reviews, see references 4 and 31). Most genetic adjuvants have had only two-to threefold effects. In this study, we examine the adjuvant activity of codelivered interferon regulatory factor (IRF) genes for DNA vaccines. IRFs are transcription factors that serve as mediators for the activation of early inflammatory responses to viral infections. The hypothesis for the study was that DNA vaccines would raise stronger immune responses if transfected cells expressed the early inflammatory factors expressed by virus-infected cells.

show abstract

DNA Immunization for Influenza Virus: Studies Using Hemagglutinin‐ and Nucleoprotein‐Expressing DNAs

Cited by 100 publications

References 6 publications

The Hybrid Cytomegalovirus Enhancer/Chicken β-Actin Promoter along with Woodchuck Hepatitis Virus Posttranscriptional Regulatory Element Enhances the Protective Efficacy of DNA Vaccines

The Hybrid Cytomegalovirus Enhancer/Chicken β-Actin Promoter along with Woodchuck Hepatitis Virus Posttranscriptional Regulatory Element Enhances the Protective Efficacy of DNA Vaccines

Recombinant Parainfluenza Virus 5 Expressing Hemagglutinin of Influenza A Virus H5N1 Protected Mice against Lethal Highly Pathogenic Avian Influenza Virus H5N1 Challenge

Regulation of DNA-Raised Immune Responses by Cotransfected Interferon Regulatory Factors

Contact Info

Product

Resources

About