DNA vaccination protects against an influenza challenge in a double-blind randomised placebo-controlled phase 1b clinical trial

Jones, Suzanne; Evans, Kirsten; McElwaine-Johnn, Hilary; Sharpe, Michaela; Oxford, John; Lambkin‐Williams, Robert; Mant, Tim; Nolan, Andrew; Zambon, Maria; Ellis, Joanna; Beadle, John; Loudon, Peter T.

doi:10.1016/j.vaccine.2009.02.061

Cited by 130 publications

(93 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Several veterinarian DNA vaccines have been approved for routine use, including a West Nile virus vaccine for horses (Davis et al, 2001) and a vaccine for the treatment of advanced canine melanoma (Bergman et al, 2003). These, together with a recent study showing that plasmid DNA vaccination in humans results in protection against influenza challenge (Jones et al, 2009), clearly show the therapeutic potential of plasmid DNA vaccination.…”

Section: Introductionmentioning

confidence: 58%

Therapeutic efficacy of a DNA vaccine targeting the endothelial tip cell antigen delta-like ligand 4 in mammary carcinoma

et al. 2010

View full text Add to dashboard Cite

The Notch ligand delta-like ligand 4 (DLL4) is an essential component expressed by endothelial tip cells during angiogenic sprouting. We have described a conceptually novel therapeutic strategy for targeting tumor angiogenesis and endothelial tip cells based on DNA vaccination against DLL4. Immunization with DLL4-encoding plasmid DNA by in vivo electroporation severely retarded the growth of orthotopically implanted mammary carcinomas in mice by induction of a nonproductive angiogenic response. Mechanistically, vaccination brought about a break in tolerance against the self-antigen, DLL4, as evidenced by the production of inhibitory and inherently therapeutic antibodies against mouse DLL4. Importantly, no evidence for a delayed wound healing response, or for toxicity associated with pharmacological blockade of DLL4 signaling, was noted in mice immunized with the DLL4 vaccine. We have thus developed a well-tolerated DNA vaccination strategy targeting the endothelial tip cells and the antigen DLL4 with proven therapeutic efficacy in mouse models of mammary carcinoma; a disease that has been reported to dramatically induce the expression of DLL4. Conceivably, induction of immunity toward principal mediators of pathological angiogenesis could provide protection against recurrent malignant disease in the adjuvant setting.

show abstract

Section: Introductionmentioning

confidence: 58%

Therapeutic efficacy of a DNA vaccine targeting the endothelial tip cell antigen delta-like ligand 4 in mammary carcinoma

et al. 2010

View full text Add to dashboard Cite

show abstract

“…One approach is new DNA vaccines with improved immunogenicity in humans 6 , 7 , 25 providing cross‐reactive cellular and humoral immune responses 26 …”

Section: Discussionmentioning

confidence: 99%

“…The first generation of DNA vaccines produced good results against homologous virus infection in mice, but poorer results in higher mammals and humans 3 , 4 . However, the new generation DNA vaccines against influenza in humans have now been shown to be immunogenic, 6 and its efficiency have been evaluated in humans 7 . DNA vaccines, either alone or in combination with other vaccines, show great promise for future human vaccines 8 …”

Section: Introductionmentioning

confidence: 99%

Pandemic influenza 1918 H1N1 and 1968 H3N2 DNA vaccines induce cross-reactive immunity in ferrets against infection with viruses drifted for decades

Bragstad

Martel

Thomsen

et al. 2010

Influenza and Other Respiratory Viruses

View full text Add to dashboard Cite

Please cite this paper as: Bragstad et al. (2010) Pandemic influenza 1918 H1N1 and 1968 H3N2 DNA vaccines induce cross‐reactive immunity in ferrets against infection with viruses drifted for decades. Influenza and Other Respiratory Viruses 5(1), 13–23. Background Alternative influenza vaccines and vaccine production forms are needed as the conventional protein vaccines do not induce broad cross‐reactivity against drifted strains. Furthermore, fast vaccine production is especially important in a pandemic situation, and broader vaccine reactivity would diminish the need for frequent change in the vaccine formulations. Objective In this study, we compared the ability of pandemic influenza DNA vaccines to induce immunity against distantly related strains within a subtype with the immunity induced by conventional trivalent protein vaccines against homologous virus challenge. Methods Ferrets were immunised by particle‐mediated epidermal delivery (gene gun) with DNA vaccines based on the haemagglutinin (HA) and neuraminidase (NA) and/or the matrix (M) and nucleoprotein genes of the 1918 H1N1 Spanish influenza pandemic virus or the 1968 H3N2 Hong Kong influenza pandemic virus. The animals were challenged with contemporary H1N1 or H3N2 viruses. Results We demonstrated that DNA vaccines encoding proteins of the original 1918 H1N1 pandemic virus induced protective cross‐reactive immune responses in ferrets against infection with a 1947 H1N1 virus and a recent 1999 H1N1 virus. Similarly, a DNA vaccine, based on the HA and NA of the 1968 H3N2 pandemic virus, induced cross‐reactive immune responses against a recent 2005 H3N2 virus challenge. Conclusions DNA vaccines based on pandemic or recent seasonal influenza genes induced cross‐reactive immunity against contemporary virus challenge as good as or superior to contemporary conventional trivalent protein vaccines. This suggests a unique ability of influenza DNA to induce cross‐protective immunity against both contemporary and long‐time drifted viruses.

show abstract

“…DNA vaccines rely on the delivery of antigen-coding DNA to the nucleus of cells, but due to the large molecular weight, anionic charge and susceptibility of DNA to enzymatic degradation physical injection of DNA often results in very low transfection efficacies. 3 Physical methods of disrupting the cell membrane such as electroporation 4 and ballistic delivery 5 have been demonstrated to enhance gene expression levels significantly in vivo. However these devices are associated with pain, 6,7 and require the use of expensive specialist equipment, making them less acceptable to patients and unsuitable for mass vaccination.…”

Section: Introductionmentioning

confidence: 99%

Dissolving microneedles for DNA vaccination: Improving functionality via polymer characterization and RALA complexation

Cole

McCaffrey

Ali

et al. 2016

Human Vaccines & Immunotherapeutics

View full text Add to dashboard Cite

DNA vaccination holds the potential to treat or prevent nearly any immunogenic disease, including cancer. To date, these vaccines have demonstrated limited immunogenicity in vivo due to the absence of a suitable delivery system which can protect DNA from degradation and improve transfection efficiencies in vivo. Recently, microneedles have been described as a novel physical delivery technology to enhance DNA vaccine immunogenicity. Of these devices, dissolvable microneedles promise a safe, pain-free delivery system which may simultaneously improve DNA stability within a solid matrix and increase DNA delivery compared to solid arrays. However, to date little work has directly compared the suitability of different dissolvable matrices for formulation of DNA-loaded microneedles. Therefore, the current study examined the ability of 4 polymers to formulate mechanically robust, functional DNA loaded dissolvable microneedles. Additionally, complexation of DNA to a cationic delivery peptide, RALA, prior to incorporation into the dissolvable matrix was explored as a means to improve transfection efficacies following release from the polymer matrix. Our data demonstrates that DNA is degraded following incorporation into PVP, but not PVA matrices. The complexation of DNA to RALA prior to incorporation into polymers resulted in higher recovery from dissolvable matrices, and increased transfection efficiencies in vitro. Additionally, RALA/DNA nanoparticles released from dissolvable PVA matrices demonstrated up to 10-fold higher transfection efficiencies than the corresponding complexes released from PVP matrices, indicating that PVA is a superior polymer for this microneedle application.

show abstract

DNA vaccination protects against an influenza challenge in a double-blind randomised placebo-controlled phase 1b clinical trial

Cited by 130 publications

References 15 publications

Therapeutic efficacy of a DNA vaccine targeting the endothelial tip cell antigen delta-like ligand 4 in mammary carcinoma

Therapeutic efficacy of a DNA vaccine targeting the endothelial tip cell antigen delta-like ligand 4 in mammary carcinoma

Pandemic influenza 1918 H1N1 and 1968 H3N2 DNA vaccines induce cross-reactive immunity in ferrets against infection with viruses drifted for decades

Dissolving microneedles for DNA vaccination: Improving functionality via polymer characterization and RALA complexation

Contact Info

Product

Resources

About