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 Targeting Murine Immune Responses to Selected T Cell- or Antibody-Defined Determinants of the Hepatitis B Surface Antigen by Plasmid DNA Vaccines Encoding Chimeric Antigen

2001 ◽  
Vol 166 (2) ◽  
pp. 1405-1413 ◽  
Author(s):  
Reinhold Schirmbeck ◽  
Xin Zheng ◽  
Michael Roggendorf ◽  
Michael Geissler ◽  
Francis V. Chisari ◽  
...  
Keyword(s):  
T Cell ◽  
Hepatitis B ◽  
Immune Responses ◽  
Surface Antigen ◽  
Plasmid Dna ◽  
Dna Vaccines ◽  
Hepatitis B Surface Antigen

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 Modulation of Immunity against Herpes Simplex Virus Infection via Mucosal Genetic Transfer of Plasmid DNA Encoding Chemokines

2001 ◽  
Vol 75 (2) ◽  
pp. 569-578 ◽  
Author(s):  
Seong Kug Eo ◽  
Sujin Lee ◽  
Sangjun Chun ◽  
Barry T. Rouse
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Immune Responses ◽  
Adaptive Immunity ◽  
Plasmid Dna ◽  
Interleukin 4 ◽  
Dna Encoding ◽  
Type Pattern ◽  
Cc Chemokines ◽  
Simplex Virus

ABSTRACT In this study, we examined the effects of murine chemokine DNA, as genetic adjuvants given mucosally, on the systemic and distal mucosal immune responses to plasmid DNA encoding gB of herpes simplex virus (HSV) by using the mouse model. The CC chemokines macrophage inflammatory protein 1β (MIP-1β) and monocyte chemotactic protein 1 (MCP-1) biased the immunity to the Th2-type pattern as judged by the ratio of immunoglobulin isotypes and interleukin-4 cytokine levels produced by CD4+ T cells. The CXC chemokine MIP-2 and the CC chemokine MIP-1α, however, mounted immune responses of the Th1-type pattern, and such a response rendered recipients more resistant to HSV vaginal infection. In addition, MIP-1α appeared to act via the upregulation of antigen-presenting cell (APC) function and the expression of costimulatory molecules (B7-1 and B7-2), whereas MIP-2 enhanced Th1-type CD4+ T-cell-mediated adaptive immunity by increasing gamma interferon secretion from activated NK cells. Our results emphasize the value of using the mucosal route to administer DNA modulators such as chemokines that function as adjuvants by regulating the activity of innate immunity. Our findings provide new insight into the value of CXC and CC chemokines, which act on different innate cellular components as the linkage signals between innate and adaptive immunity in mucosal DNA vaccination.

scholarly journals Neonates Mount Robust and Protective Adult-Like CD8+-T-Cell Responses to DNA Vaccines

2002 ◽  
Vol 76 (23) ◽  
pp. 11911-11919 ◽  
Author(s):  
Jie Zhang ◽  
Nicole Silvestri ◽  
J. Lindsay Whitton ◽  
Daniel E. Hassett
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Viral Infections ◽  
Dna Vaccines ◽  
Neonatal Period ◽  
Cytotoxic T Cells ◽  
Lymphocytic Choriomeningitis ◽  
Cell Responses ◽  
Rapid Induction

ABSTRACT Neonates are thought to mount less vigorous adaptive immune responses than adults to antigens and infectious agents. This concept has led to a delay in the administration of many currently available vaccines until late infancy or early childhood. It has recently been shown that vaccines composed of plasmid DNA can induce both humoral and cell-mediated antimicrobial immunity when administered within hours of birth. In most of these studies, immune responses were measured weeks or months after the initial vaccination, and it is therefore questionable whether the observed responses were actually the result of priming of splenocytes within the neonatal period. Here we show that DNA vaccination at birth results in the rapid induction of antigen-specific CD8+ T cells within neonatal life. Analyses of T-cell effector functions critical for the resolution of many viral infections revealed that neonatal and adult CD8+ T cells produce similar arrays of cytokines. Furthermore, the avidities of neonatal and adult CD8+ T cells for peptide and the rapidity with which they upregulate cytokine production after recall encounters with antigen are similar. Protective immunity against the arenavirus lymphocytic choriomeningitis virus, which is mediated by CD8+ cytotoxic T cells, is also rapidly acquired within the neonatal period. Collectively these data imply that, at least in the case of CD8+ T cells, neonates are not as immunodeficient as previously supposed and that DNA vaccines may be an effective and safe means of providing critical cell-mediated antiviral immunity extremely early in life.

scholarly journals Dendritic Cell Mediated Delivery of Plasmid DNA Encoding LAMP/HIV-1 Gag Fusion Immunogen Enhances T Cell Epitope Responses in HLA DR4 Transgenic Mice

PLoS ONE ◽  
2010 ◽  
Vol 5 (1) ◽  
pp. e8574 ◽  
Author(s):  
Gregory G. Simon ◽  
Yongli Hu ◽  
Asif M. Khan ◽  
Jingshi Zhou ◽  
Jerome Salmon ◽  
...  
Keyword(s):  
T Cell ◽  
Dendritic Cell ◽  
Transgenic Mice ◽  
Plasmid Dna ◽  
Cell Epitope ◽  
T Cell Epitope ◽  
Dna Encoding ◽  
Hiv 1

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.

Sign in / Sign up

Export Citation Format

Share Document