DNA Vaccine
A DNA vaccine is a type of vaccine that uses genetically engineered DNA to stimulate an immune response against a specific pathogen. The DNA encoding the antigen is injected into the body, where it is taken up by cells and used to produce the antigen, triggering an immune response. This approach has the potential to be more stable and cost-effective than traditional vaccines.
7 Key excerpts on "DNA Vaccine"
eBook - ePubVaccinology
An Essential Guide
- Gregg N. Milligan, Alan D. T. Barrett, Gregg N. Milligan, Alan D. T. Barrett(Authors)
- 2014(Publication Date)
- Wiley-Blackwell(Publisher)
...Experimental DNA Vaccines, which encode the TNF-α gene under the control of a viral promoter, suggest that immunizing against a host-produced immune mediator can be effective in treating autoimmune diseases. This type of treatment strategy has potential pros and cons compared to treating with anti-TNF-α antibodies or soluble receptors. While the half-life of these proteins is short compared to the immunological memory produced by vaccination, could the short half-life be advantageous? What are the long-term effects of raising antibodies against an important immune regulator? As laboratory studies continue to define the basic immune mechanisms that underlie both the disease and the response, we will be better placed to answer these questions. Definition DNA Vaccine : A vaccine that is administered in the form of a DNA molecule that contains the gene encoding for the antigen under the control of appropriate promoter and regulatory sequences to allow the transcription and subsequent translation by the host cell after vaccine administration. The DNA molecule can be engineered to encode protein adjuvants such as cytokines and chemokines. The first licensed DNA Vaccine is an equine vaccine against West Nile virus; there are currently no DNA Vaccines licensed for human use. Immunology of Protection and Adjuvants As we continue to move forward with the rational design of novel vaccines, as opposed to attempting to attenuate live pathogens by serial passage, understanding the role of the various immune effectors in controlling the infection becomes increasingly relevant. In particular, the relative balance of cell-mediated immunity versus humoral mechanisms, such as antibodies, can be critically important in determining protection. With the emergence of DNA Vaccines, new strategies for enhancing immune responses are gaining importance...
eBook - ePub- Jiri Mestecky, Michael E. Lamm, Pearay L. Ogra, Warren Strober, John Bienenstock, Jerry R. McGhee, Lloyd Mayer(Authors)
- 2005(Publication Date)
- Academic Press(Publisher)
...Chapter 60 DNA Vaccines for Mucosal Immunity to Infectious Diseases John E. Herrmann Division of Infectious Diseases and Immunology, University of Massachusetts Medical, School, Worcester, Massachusetts Harriet L. Robinson Division of Microbiology and Immunology, Yerkes Primate Research Center of Emory, University, Atlanta, Georgia DNA Vaccines are plasmid DNAs encoding specific proteins that can be expressed in cells of an inoculated host. The plasmids used are eukaryotic expression vectors, which contain the necessary elements for expression in eukaryotic cells. Plasmid DNAs encoding α-galactosidase, luciferase, or acetylcholine transferase expressed these enzymes in muscle cells after injection of the plasmid into the quadriceps of mice (Wolff et al., 1990). Enzyme production in muscle tissue was detected up to 2 months after inoculation. Others have described production of antibodies to human growth hormone by gene gun immunization of DNA-coated gold microparticles, demonstrating that plasmid DNAs could be administered by this route and elicit antibody production (Tang et al., 1992). The first DNA Vaccines that demonstrated protective immunity in animal models were described in 1993 for plasmids encoding influenza hemagglutinin (Robinson et al., 1993 ; Fynan et al., 1993) and influenza nucleoprotein (Ulmer et al., 1993). Most studies to date have involved administration of DNA Vaccines by intramuscular, intravenous, or intradermal injection or by gene-gun delivery of DNA-coated particles into the epidermis. Of these methods, gene-gun delivery requires the least amount of DNA to induce immune responses (Fynan et al., 1993 ; Robinson et al., 1997). DNA Vaccines have inherent advantages over traditional inactivated whole microbial vaccines and subunit vaccines. For one, they do not require the use of purified proteins or viral vectors...
eBook - ePubVaccines for Cancer Immunotherapy
An Evidence-Based Review on Current Status and Future Perspectives
- Nima Rezaei, Mahsa Keshavarz-Fathi(Authors)
- 2018(Publication Date)
- Academic Press(Publisher)
...Alternatively, RNA vaccines can be developed for the efficient production and secretion of extracellular antigens to trigger B cell responses and production of antigen-specific antibody. In addition, the effectiveness of RNA vaccines may be associated with the fact that RNA is known to be a potent stimulator of innate immunity. It has been demonstrated that mRNA activates dendritic cells and monocytes in vitro in a MyD88-dependent fashion involving signaling via TLR. 16, 17 In vivo studies have shown that an mRNA vaccine resulted in the upregulation of different genes involved in cell activation and chemotaxis 18 and also induced TLR7-dependent CD4+ and CD8+ T cell responses, as well as antitumor immunity. 19 DNA Vaccine DNA Vaccines are modalities that are expressed within the host cells, but they are not capable of replication. They can be produced to imitate the safety and specificity of subunit vaccines. DNA Vaccines can trigger immune responses as similar to live-attenuated vaccine types while resulting in no pathogenic infection in vivo. Administering DNA Vaccines directly into the host lead to expression of the antigenic protein from the host cells. This process induces both antigen-specific antibody and cellular responses. 20 – 22 Also, applications of DNA Vaccines are thought to show safety, stability, and cost-effectiveness, and are simply and rapidly engineered by recent technologies of recombinant DNA. 23 To deliver DNA Vaccines to the target, different approaches including vectors such as viral vectors, naked DNA, liposome and polymer complex; and physical techniques of delivery such as electroporation, ultrasound, and particle-mediated epidermal delivery have been developed. 24 Most of the DNA Vaccine studies have used skin or muscle as a target of immunization to deliver DNA Vaccines. DNA Vaccines are collected and expressed by muscle cells and local APCs in intramuscular injection...
eBook - ePubBiologics and Biosimilars
Drug Discovery and Clinical Applications
- Xiaodong Feng, Hong-Guang Xie, Ashim Malhotra, Catherine F. Yang, Xiaodong Feng, Hong-Guang Xie, Ashim Malhotra, Catherine F. Yang(Authors)
- 2022(Publication Date)
- CRC Press(Publisher)
...These motifs can act as pathogen-associated molecular patterns (PAMPs), which activate the innate immune system via PRRs and eventually induce adaptive immune responses such as the release of Th1 cytokines [26]. In practice, DNA Vaccines are effective when vaccinating small animals [53], but have struggled when used to vaccinate humans. Though DNA Vaccines are easier to store than their mRNA counterparts due to their stability and succeed in generating both cell-mediated and humoral immune responses, they tend to require large bolus doses since they do not elicit an adequate antibody response [53]. Additionally, they carry risks of vaccine-induced thrombotic thrombocytopenia (VITT), as seen during the trials of the Oxford-AstraZeneca COVID-19 vaccine [ 54 ]. 4.5.4.2 mRNA vaccines Within the central dogma of molecular biology, DNA gets transcribed into mRNA, which then gets translated into protein [52]. The transition from DNA to mature mRNA requires different regulatory processes and splicing mechanisms. Unlike DNA Vaccine strategies, mRNA vaccines are already in a processed form, thus preventing any uncontrolled splicing by the host cell. In practice, mRNA vaccines utilize host translational machinery to produce the target antigen, which will subsequently initiate an adaptive immune response. After inoculation, the mRNA vaccine is internalized by resident nonimmune cells at the injection site. The mRNA is then expressed, which stimulates select PRRs of the innate immune system, such as RIG-1 and MDA5. This stimulation starts a domino effect which leads to the upregulation of signaling molecules, like cytokines and chemokines, that recruit immune cells. This process leads to the activation of cytotoxic T cells through MHC-I and helper T cells and B cells through MHC-II...
eBook - ePub- Phoebe Lostroh(Author)
- 2019(Publication Date)
- Garland Science(Publisher)
...There is, however, a veterinary DNA Vaccine that protects horses from West Nile virus (WNV, a flavivirus; see Chapter 5). The DNA encodes the WNV matrix and envelope proteins. DNA Vaccines usually are produced by cloning DNA-encoding immunogenic proteins under the control of a viral promoter that will result in strong expression once the DNA enters the nucleus of a human cell. These antigens will then be displayed as endogenous foreign antigens in MHC-I, prompting the development of an adaptive immune response. Another variation of subunit vaccination is the use of viruslike particles (VLPs), which are assembled from one or more viral capsomeres but do not contain any genetic material (Figure 16.6). VLPs are more immunogenic than the same capsomeres if they are not first assembled into a VLP. The current prophylactic HPV vaccines are composed of VLPs that contain capsomeres L1 and L2 (see Chapter 8). Figure 16.6 Viruslike particles. VLPs are assembled from viral capsomeres but do not contain any genetic material. 16.5 Although seasonal influenza vaccines are useful, a universal flu vaccine is highly sought after Influenza A virus (IAV) is a major pathogen that causes millions of serious infections and 250,000–500,000 deaths every year. As an RNA virus, IAV has an RNA-dependent RNA polymerase with a high intrinsic misincorporation rate, so IAV exhibits high rates of antigenic variation (see Chapters 5, 15, and 17). Furthermore, IAV has a segmented genome in which major antigenic proteins are encoded by different segments (Figure 16.7). This genome configuration makes it possible for two different influenza viruses to co-infect the same cell and have recombinant offspring with a new combination of genome segments, which is the origin of most pandemic influenza strains (see Chapter 17). Both of these forms of genetic variation are problematic for vaccine development...
eBook - ePubIntroductory Immunology
Basic Concepts for Interdisciplinary Applications
- Jeffrey K. Actor(Author)
- 2019(Publication Date)
- Academic Press(Publisher)
...Major advances in vaccine design are taking place. Improvements in methodologies to produce nonvirulent antigenic substances for use as vaccine antigens will dictate future successes in the immunization arena. These include novel ways to manufacture toxoids and synthetic peptides, improvements in recombinant DNA technology to allow live, avirulent (nondisease-causing) viral and bacterial agents to express other pathogen genes, development of DNA-based vaccines, and new methods of conjugation to achieve superior immunogenicity for both polysaccharide and protein antigens. Table 9.1 Vaccine Classes and Their Targets Type of vaccine Components Examples Live, attenuated Viral or bacterial organism with reduced pathogenicity Oral polio, varicella, measles-mumps-rubella (MMR), bacillus Calmette-Guerin (BCG) Killed-inactivated Whole killed organism Inactivated polio, typhoid Subunit Recombinant subunit Inactivated or modified toxins, purified components Gene-derived proteins produced in another organism Diphtheria, tetanus, influenza Hepatitis B toxoid, human papillomavirus (HPV) Conjugate/polyvalent Combined components isolated or genetically modified from multiple strains Haemophilus influenzae type B, Streptococcus pneumonia, Neisseria meningitidis Basic Concepts of Protective Immunization The objective of immunization is to generate high levels of memory cells using vaccination methods (Fig. 9.1). The term primary immune response refers to a lymphocyte activation event following first recognition of foreign material, following which a memory response is generated. Immunological memory represents a pool of circulating, long-lived cells that remain present and available for action long after the initial response activities wane. If the antigen is reencountered at a later time, a secondary immune response occurs, in which memory cells are engaged and activated. This secondary response is faster, more focused, and more effective than the original encounter. Fig...
eBook - ePub- Julius M. Cruse, Robert E. Lewis(Authors)
- 2009(Publication Date)
- CRC Press(Publisher)
...V V28 An orphan chemokine receptor expressed in neural and lymphoid tissue and on the THP-1 cell line. The tissue sources are peripheral blood mononuclear cells. vaccinable Capable of being vaccinated successfully. vaccinate To inoculate with a vaccine to induce immunity against a disease. vaccination Immunization against infectious disease through the administration of vaccines that produce active (protective) immunity in humans and other animals. It may be induced with killed, attenuated, or nonpathogenic forms of a pathogenic agent or its antigens to generate protective adaptive immune responses characterized by antigen-specific memory T cells and memory B cells specific for the pathogen. Subsequent exposure to the pathogen will then induce a secondary or anamnestic response. vaccine Live attenuated or killed microorganisms, or their parts or products containing antigens, that stimulate a specific immune response consisting of protective antibodies and T cell immunity. A vaccine should stimulate a sufficient number of memory T and B lymphocytes to yield effector T cells and antibody-producing B cells. It should also be able to stimulate high titers of neutralizing antibodies. Injection of a vaccine into a nonimmune subject induces active immunity against the modified pathogen. Other than macromolecular components, a vaccine may consist of a plasmid that contains a cDNA encoding an antigen of a microorganism. Other vaccines include anti-insect vector vaccines, fertility control vaccines, peptide-based preparations, anti-idiotype preparations, and DNA Vaccines. No antiparasite vaccine manufactured by conventional technology is in use at present. Vaccines may be prepared from weakened or killed microorganisms, inactivated toxins, toxoids derived from microorganisms, or immunologically active surface markers of microorganisms. They can be administered intramuscularly, subcutaneously, intradermally, orally, or intranasally, as single agents or in combination...
