scholarly journals Pandemic Preparedness Against Influenza: DNA Vaccine for Rapid Relief

2021 ◽  
Vol 12 ◽  
Author(s):  
Tor Kristian Andersen ◽  
Johanna Bodin ◽  
Fredrik Oftung ◽  
Bjarne Bogen ◽  
Siri Mjaaland ◽  
...  
Keyword(s):  
Single Dose ◽  
T Cell ◽  
Dna Vaccine ◽  
Dna Vaccines ◽  
T Cell Responses ◽  
Cytotoxic T Cell ◽  
Pandemic Preparedness ◽  
Vaccine Platform ◽  
Naked Dna ◽  
Cell Responses

The 2009 “swine flu” pandemic outbreak demonstrated the limiting capacity for egg-based vaccines with respect to global vaccine supply within a timely fashion. New vaccine platforms that efficiently can quench pandemic influenza emergences are urgently needed. Since 2009, there has been a profound development of new vaccine platform technologies with respect to prophylactic use in the population, including DNA vaccines. These vaccines are particularly well suited for global pandemic responses as the DNA format is temperature stable and the production process is cheap and rapid. Here, we show that by targeting influenza antigens directly to antigen presenting cells (APC), DNA vaccine efficacy equals that of conventional technologies. A single dose of naked DNA encoding hemagglutinin (HA) from influenza/A/California/2009 (H1N1), linked to a targeting moiety directing the vaccine to major histocompatibility complex class II (MHCII) molecules, raised similar humoral immune responses as the adjuvanted split virion vaccine Pandemrix, widely administered in the 2009 pandemic. Both vaccine formats rapidly induced serum antibodies that could protect mice already 8 days after a single immunization, in contrast to the slower kinetics of a seasonal trivalent inactivated influenza vaccine (TIV). Importantly, the DNA vaccine also elicited cytotoxic T-cell responses that reduced morbidity after vaccination, in contrast to very limited T-cell responses seen after immunization with Pandemrix and TIV. These data demonstrate that DNA vaccines has the potential as a single dose platform vaccine, with rapid protective effects without the need for adjuvant, and confirms the relevance of naked DNA vaccines as candidates for pandemic preparedness.

scholarly journals Vaccination with a Shigella DNA Vaccine Vector Induces Antigen-Specific CD8+ T Cells and Antiviral Protective Immunity

2001 ◽  
Vol 75 (20) ◽  
pp. 9665-9670 ◽  
Author(s):  
Mohamed T. Shata ◽  
David M. Hone
Keyword(s):  
T Cell ◽  
Dna Vaccine ◽  
Protective Immunity ◽  
Dna Vaccines ◽  
T Cell Responses ◽  
T Cell Response ◽  
Vaccine Vector ◽  
Host Cells ◽  
Cell Responses ◽  
Hiv 1

ABSTRACT A prototype Shigella human immunodeficiency virus type 1 (HIV-1) gp120 DNA vaccine vector was constructed and evaluated for immunogenicity in a murine model. For comparative purposes, mice were also vaccinated with a vaccinia virus-env(vaccinia-env) vector or the gp120 DNA vaccine alone. Enumeration of the CD8+-T-cell responses to gp120 after vaccination using a gamma interferon enzyme-linked spot assay revealed that a single intranasal dose of the Shigella HIV-1 gp120 DNA vaccine vector elicited a CD8+ T-cell response to gp120, the magnitude of which was comparable to the sizes of the analogous responses to gp120 that developed in mice vaccinated intraperitoneally with the vaccinia-env vector or intramuscularly with the gp120 DNA vaccine. In addition, a single dose of the Shigella gp120 DNA vaccine vector afforded significant protection against a vaccinia-env challenge. Moreover, the number of vaccinia-env PFU recovered in mice vaccinated intranasally with the Shigella vector was about fivefold less than the number recovered from mice vaccinated intramuscularly with the gp120 DNA vaccine. Since theShigella vector did not express detectable levels of gp120, this report confirms that Shigella vectors are capable of delivering passenger DNA vaccines to host cells and inducing robust CD8+ T-cell responses to antigens expressed by the DNA vaccines. Furthermore, to our knowledge, this is the first documentation of antiviral protective immunity following vaccination with a live Shigella DNA vaccine vector.

scholarly journals A Novel DNA Vaccine Platform Enhances Neo-antigen-like T Cell Responses against WT1 to Break Tolerance and Induce Anti-tumor Immunity

2017 ◽  
Vol 25 (4) ◽  
pp. 976-988 ◽  
Author(s):  
Jewell N. Walters ◽  
Bernadette Ferraro ◽  
Elizabeth K. Duperret ◽  
Kimberly A. Kraynyak ◽  
Jaemi Chu ◽  
...  
Keyword(s):  
T Cell ◽  
Dna Vaccine ◽  
Tumor Immunity ◽  
T Cell Responses ◽  
Vaccine Platform ◽  
Cell Responses

scholarly journals An all-in-one adjuvanted therapeutic cancer vaccine targeting dendritic cell cytosol induces long-lived tumor suppression through NLRC4 inflammasome activation

2021 ◽  
Author(s):  
Sao Puth ◽  
Vivek Verma ◽  
Seol Hee Hong ◽  
Wenzhi Tan ◽  
Shee Eun Lee ◽  
...  
Keyword(s):  
T Cell ◽  
Cancer Vaccine ◽  
Tumor Antigen ◽  
T Cell Responses ◽  
Cytotoxic T Cell ◽  
Inflammasome Activation ◽  
Vaccine Platform ◽  
Term Survival ◽  
Cell Responses

Abstract Therapeutic cancer vaccines (TCVs) should induce robust tumor-specific T cell responses. To achieve this, TCVs incorporate T cell epitopes and strong adjuvants. Here, we report an all-in-one adjuvanted cancer vaccine platform, which targets intracellular compartment of antigen presenting cells and subsequently induces effective cytotoxic T cell responses. We screened a novel peptide (DCpep6) that specifically binds and tranmits into CD11c+ cells through in vivo phage biopanning. We then engineered a protein-based TCV (DEF) consisting of DCpep6 (D), an optimized HPV E7 tumor antigen (E), and a built-in flagellin adjuvant (F) as a single molecule. DEF was stably expressed and each component was functional. In vivo administered DEF rapidly biodistributed in draining LNs and internalized into CD11c+ cells. DEF immunization elicited strong anti-tumor T cell responses and provided long-term survival of TC-1 tumor implanted mice. The DEF-mediated anti-tumor effect was abolished in NLRC4−/− mice. Taken together, we propose a protein-based all-in-one TCV platform that intracellularly co-delivers tumor antigen and inflammasome activator to DCs to induce long-lasting anti-tumor T cell responses.

scholarly journals A single dose of HIV DNA vaccine induces long lasting potent HIV-specific T cell responses in Rhesus macaques

Retrovirology ◽  
2009 ◽  
Vol 6 (Suppl 2) ◽  
pp. P21
Author(s):  
Géraldine Arrode-Brusés ◽  
Darlene Sheffer ◽  
Ramakrishna Hegde ◽  
Zhengian Liu ◽  
Francois Villenger ◽  
...  
Keyword(s):  
Single Dose ◽  
T Cell ◽  
Dna Vaccine ◽  
Rhesus Macaques ◽  
T Cell Responses ◽  
Cell Responses ◽  
Hiv Dna

scholarly journals Combined Administration with DNA Encoding Vesicular Stomatitis Virus G Protein Enhances DNA Vaccine Potency

2009 ◽  
Vol 84 (5) ◽  
pp. 2331-2339 ◽  
Author(s):  
Chih-Ping Mao ◽  
Chien-Fu Hung ◽  
Tae Heung Kang ◽  
Liangmei He ◽  
Ya-Chea Tsai ◽  
...  
Keyword(s):  
T Cell ◽  
Dna Vaccine ◽  
Vesicular Stomatitis Virus ◽  
Viral Infections ◽  
Dna Vaccines ◽  
T Cell Responses ◽  
Dna Encoding ◽  
Cell Responses ◽  
Prevention And Treatment ◽  
Vesicular Stomatitis

ABSTRACT DNA vaccines have recently emerged at the forefront of approaches to harness the immune system in the prevention and treatment of viral infections, as well as the prevention and treatment of cancers. However, these vaccines suffer from limited efficacy since they often fail to produce significant antigen-specific CD8+ T-cell responses. We report here a novel concept for DNA vaccine design that exploits the unique and powerful ability of viral fusogenic membrane glycoproteins (FMGs) to couple concentrated antigen transfer to dendritic cells (DCs) with local induction of the acute inflammatory response. Intramuscular administration into mice by electroporation technology of a plasmid containing the FMG gene from vesicular stomatitis virus (VSV-G)—together with DNA encoding the E7 protein of human papillomavirus type 16, a model cervical cancer antigen—elicited robust E7-specific CD8+ T-cell responses, as well as therapeutic control of E7-expressing tumors. This effect could potentially be mediated through the immunogenic form of cellular fusion and necrosis induced by VSV-G, which in a concerted fashion provokes leukocyte infiltration into the inoculation site, enhances cross-presentation of antigen to DCs, and stimulates them to mature efficiently. Thus, the incorporation of FMGs into DNA vaccines holds promise for the successful control of viral infections and cancers in the clinic.

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