Extended immunization intervals enhance the immunogenicity and protective efficacy of plasmid DNA vaccines

2007 ◽  
Vol 9 (12-13) ◽  
pp. 1439-1446 ◽  
Author(s):  
Gary T. Brice ◽  
Carlota Dobaño ◽  
Martha Sedegah ◽  
Maureen Stefaniak ◽  
Norma L. Graber ◽  
...  
Keyword(s):  
Plasmid Dna ◽  
Dna Vaccines ◽  
Protective Efficacy

scholarly journals Induction of mucosal and systemic immune response by single-dose oral immunization with biodegradable microparticles containing DNA encoding HBsAg

2005 ◽  
Vol 86 (3) ◽  
pp. 601-610 ◽  
Author(s):  
Xiao-Wen He ◽  
Fang Wang ◽  
Lei Jiang ◽  
Jun Li ◽  
Shan-kui Liu ◽  
...  
Keyword(s):  
Single Dose ◽  
Plasmid Dna ◽  
Dna Vaccines ◽  
Oral Immunization ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Pcr Analysis ◽  
Target Antigen ◽  
Dna Encoding ◽  
Plga Microparticles

The purpose of this work was to assess the ability of plasmid DNA encoding hepatitis B virus (HBV) HBsAg encapsulated in poly(dl-lactide-co-glycolic acid) (PLGA) microparticles to induce local and systemic HBsAg-specific immunity following a single dose of oral immunization. RT-PCR analysis demonstrated prolonged transcription of plasmid DNA, consistent with the sustained expression and presentation of target antigen observed by confocal laser scanning microscopy, in gut-associated lymphocyte tissue (GALT) from mice immunized orally with plasmid DNA encapsulated into PLGA microparticles. Oral administration of PLGA-DNA microparticles induced a long-lasting and stable antigen-specific antibody response, both serum total antibody and intestinal IgA, in BALB/c mice. Mice immunized orally exhibited antigen-specific gamma interferon production and cytotoxic T lymphocyte responses in spleen and GALT after restimulation in vitro with HBsAg or tumour cells stably expressing HBsAg. In contrast, naked DNA vaccines given by intramuscular injection induced only systemic cellular and humoral responses to HBsAg, which were much lower than the responses elicited by oral DNA encapsulated in PLGA microparticles at equivalent doses. The results are encouraging with regard to obtaining good compliance and vaccination coverage with candidate plasmid DNA vaccines, especially in developing countries.

scholarly journals Improved Tuberculosis DNA Vaccines by Formulation in Cationic Lipids

2002 ◽  
Vol 70 (7) ◽  
pp. 3681-3688 ◽  
Author(s):  
S. D'Souza ◽  
V. Rosseels ◽  
O. Denis ◽  
A. Tanghe ◽  
N. De Smet ◽  
...  
Keyword(s):  
Dna Vaccines ◽  
Protective Efficacy ◽  
Interleukin 2 ◽  
Cationic Lipids ◽  
Relative Light Unit ◽  
Phosphate Binding ◽  
Cytolytic T Lymphocyte ◽  
Igg Isotypes ◽  
Phosphate Binding Protein ◽  
Lymphocyte Responses

ABSTRACT Mice were vaccinated with plasmid DNA (pDNA) encoding antigen 85A (Ag85A), Ag85B, or PstS-3 from Mycobacterium tuberculosis either in saline or formulated for intramuscular injections in VC1052:DPyPE (aminopropyl-dimethyl-myristoleyloxy-propanaminium bromide-diphytanoylphosphatidyl-ethanolamine) (Vaxfectin; Vical, Inc., San Diego, Calif.) or for intranasal instillations in GAP-DLRIE:DOPE (aminopropyl-dimethyl-bis-dodecyloxy-propanaminium bromide-dioleoylphosphatidyl-ethanolamine). These two novel cationic and neutral colipid formulations were previously reported to be effective adjuvants for pDNA-induced antibody responses. The levels of Ag85-specific total immunoglobulin G (IgG) and IgG isotypes were all increased 3- to 10-fold by formulation of pDNA in Vaxfectin. The level of production of splenic T-cell-derived Th1-type cytokines (interleukin-2 and gamma interferon) in response to purified Ag85 and to synthetic peptides spanning the entire Ag85A protein was also significantly higher in animals vaccinated with pDNA formulated in Vaxfectin. Cytolytic T-lymphocyte responses generated by pDNA encoding phosphate-binding protein PstS-3 in Vaxfectin were better sustained over time than were those generated by PstS-3 DNA in saline. Intranasal immunization with Ag85A DNA in saline was completely ineffective, whereas administration in GAP-DLRIE:DOPE induced a positive Th1-type cytokine response; however, the extent of the latter response was clearly lower than that obtained following intramuscular immunization with the same DNA dose. Combined intramuscular and intranasal administrations in cationic lipids resulted in stronger immune responses in the spleen and, more importantly, in the lungs as well. Finally, formulation in Vaxfectin increased the protective efficacy of the Ag85B DNA vaccine, as measured by reduced relative light unit counts and CFU counts in the spleen and lungs from mice challenged with bioluminescent M. tuberculosis H37Rv. These results may be of importance for future clinical use of DNA vaccines in humans.

scholarly journals A Comparison of Plasmid DNA and mRNA as Vaccine Technologies

Vaccines ◽  
2019 ◽  
Vol 7 (2) ◽  
pp. 37 ◽  
Author(s):  
Liu
Keyword(s):  
Clinical Trials ◽  
Dna Vaccine ◽  
Plasmid Dna ◽  
Dna Vaccines ◽  
Delivery Systems ◽  
Potential Toxicity ◽  
Vaccine Candidates ◽  
The Status ◽  
Experimental Findings ◽  
Theoretical Issues

This review provides a comparison of the theoretical issues and experimental findings for plasmid DNA and mRNA vaccine technologies. While both have been under development since the 1990s, in recent years, significant excitement has turned to mRNA despite the licensure of several veterinary DNA vaccines. Both have required efforts to increase their potency either via manipulating the plasmid DNA and the mRNA directly or through the addition of adjuvants or immunomodulators as well as delivery systems and formulations. The greater inherent inflammatory nature of the mRNA vaccines is discussed for both its potential immunological utility for vaccines and for the potential toxicity. The status of the clinical trials of mRNA vaccines is described along with a comparison to DNA vaccines, specifically the immunogenicity of both licensed veterinary DNA vaccines and select DNA vaccine candidates in human clinical trials.

Plasmid DNA encoding influenza virus haemagglutinin induces Th1 cells and protection against respiratory infection despite its limited ability to generate antibody responses

Microbiology ◽  
2000 ◽  
Vol 81 (7) ◽  
pp. 1737-1745 ◽  
Author(s):  
Patricia A. Johnson ◽  
Margaret A. Conway ◽  
Janet Daly ◽  
Carolyn Nicolson ◽  
James Robertson ◽  
...  
Keyword(s):  
Influenza Virus ◽  
T Cell ◽  
Immune Responses ◽  
Plasmid Dna ◽  
Dna Vaccines ◽  
Dose Range ◽  
Th1 Cells ◽  
Dna Encoding ◽  
Live Virus ◽  
Limited Ability

Direct intramuscular injection of plasmid DNA can generate immune responses against encoded antigens. However, the relative ability of DNA vaccines to induce cellular and humoral immunity after a single or booster immunization and the persistence of this response have not been fully elucidated. In this study, induction and maintenance of antibody and T cell subtypes with different doses of naked DNA encoding the haemagglutinin (HA) gene of influenza virus were examined and compared to the immune responses and protection induced by respiratory tract infection and immunization with a killed virus vaccine. Like natural infection, immunization with HA DNA induced potent Th1 responses. Spleen cells from mice immunized once with HA DNA in the dose range 10 ng to 100 μg secreted significant levels of IFN-γ, but low or undetectable IL-5, in response to influenza virus in vitro. Furthermore, CD4+ HA-specific Th1 clones were generated from spleens of immunized mice. Although T cell responses waned 12 weeks after a single immunization, antigen-specific Th1 cells persisted in the spleen for at least 6 months after two booster immunizations. In contrast, influenza virus-specific ELISA IgG titres were low after a single immunization and required two booster immunizations to reach significant levels. Furthermore, haemagglutination inhibition (HI) antibodies were weak or undetectable after two immunizations. Nevertheless, two doses of HA DNA conferred almost complete protection against respiratory challenge with live virus. Thus, despite the limited ability to induce antibodies, DNA vaccines confer protective immunity against influenza virus infection, which appears to be mediated by Th1 cells.

scholarly journals Engineered Nanodelivery Systems to Improve DNA Vaccine Technologies

Pharmaceutics ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 30 ◽  
Author(s):  
Michael Lim ◽  
Abu Zayed Md Badruddoza ◽  
Jannatul Firdous ◽  
Mohammad Azad ◽  
Adnan Mannan ◽  
...  
Keyword(s):  
Immune Responses ◽  
Clinical Application ◽  
Dna Vaccine ◽  
Immune Cells ◽  
Plasmid Dna ◽  
Dna Vaccines ◽  
Immunological Response ◽  
Main Challenge ◽  
Human Immunodeficiency Viruses ◽  
Stimulation Of

DNA vaccines offer a flexible and versatile platform to treat innumerable diseases due to the ease of manipulating vaccine targets simply by altering the gene sequences encoded in the plasmid DNA delivered. The DNA vaccines elicit potent humoral and cell-mediated responses and provide a promising method for treating rapidly mutating and evasive diseases such as cancer and human immunodeficiency viruses. Although this vaccine technology has been available for decades, there is no DNA vaccine that has been used in bed-side application to date. The main challenge that hinders the progress of DNA vaccines and limits their clinical application is the delivery hurdles to targeted immune cells, which obstructs the stimulation of robust antigen-specific immune responses in humans. In this updated review, we discuss various nanodelivery systems that improve DNA vaccine technologies to enhance the immunological response against target diseases. We also provide possible perspectives on how we can bring this exciting vaccine technology to bedside applications.

scholarly journals Influences of Glycosylation on Antigenicity, Immunogenicity, and Protective Efficacy of Ebola Virus GP DNA Vaccines

2006 ◽  
Vol 81 (4) ◽  
pp. 1821-1837 ◽  
Author(s):  
William Dowling ◽  
Elizabeth Thompson ◽  
Catherine Badger ◽  
Jenny L. Mellquist ◽  
Aura R. Garrison ◽  
...  
Keyword(s):  
T Cell ◽  
Protective Immunity ◽  
Ebola Virus ◽  
Dna Vaccines ◽  
Protective Efficacy ◽  
T Cell Epitopes ◽  
Glycosylation Sites ◽  
Membrane Bound ◽  
Antibody Epitopes

ABSTRACT The Ebola virus (EBOV) envelope glycoprotein (GP) is the primary target of protective immunity. Mature GP consists of two disulfide-linked subunits, GP1 and membrane-bound GP2. GP is highly glycosylated with both N- and O-linked carbohydrates. We measured the influences of GP glycosylation on antigenicity, immunogenicity, and protection by testing DNA vaccines comprised of GP genes with deleted N-linked glycosylation sites or with deletions in the central hypervariable mucin region. We showed that mutation of one of the two N-linked GP2 glycosylation sites was highly detrimental to the antigenicity and immunogenicity of GP. Our data indicate that this is likely due to the inability of GP2 and GP1 to dimerize at the cell surface and suggest that glycosylation at this site is required for achieving the conformational integrity of GP2 and GP1. In contrast, mutation of two N-linked sites on GP1, which flank previously defined protective antibody epitopes on GP, may enhance immunogenicity, possibly by unmasking epitopes. We further showed that although deleting the mucin region apparently had no effect on antigenicity in vitro, it negatively impacted the elicitation of protective immunity in mice. In addition, we confirmed the presence of previously identified B-cell and T-cell epitopes in GP but show that when analyzed individually none of them were neither absolutely required nor sufficient for protective immunity to EBOV. Finally, we identified other potential regions of GP that may contain relevant antibody or T-cell epitopes.

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