A genetic vaccine (also ''gene-based vaccine'') is a

vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifi ...

that contains

nucleic acids Nucleic acids are large biomolecules that are crucial in all cells and viruses. They are composed of nucleotides, which are the monomer components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main classes of nucleic a ...

such as

DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...

RNA Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...

that lead to

protein biosynthesis Protein biosynthesis, or protein synthesis, is a core biological process, occurring inside Cell (biology), cells, homeostasis, balancing the loss of cellular proteins (via Proteolysis, degradation or Protein targeting, export) through the produc ...

antigen In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

s within a cell. Genetic vaccines thus include DNA vaccines, RNA vaccines and

viral vector vaccine A viral vector vaccine is a vaccine that uses a viral vector to deliver genetic material (DNA) that can be transcribed by the recipient's host cells as mRNA coding for a desired protein, or antigen, to elicit an immune response. , six viral vector ...

Properties

Most vaccines other than live attenuated vaccines and genetic vaccines are not taken up by MHC-I-presenting cells, but act outside of these cells, producing only a strong

humoral immune response Humoral immunity is the aspect of immunity that is mediated by macromolecules – including secreted antibodies, complement proteins, and certain antimicrobial peptides – located in extracellular fluids. Humoral immunity is named so because ...

via

antibodies An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...

. In the case of intracellular pathogens, an exclusive humoral immune response is ineffective.Eckhart Buddecke: ''Molekulare Medizin.'' ecomed-Storck GmbH, 2002, ISBN 3609160918. S. 162. Genetic vaccines are based on the principle of uptake of a nucleic acid into cells, whereupon a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

is produced according to the nucleic acid template. This protein is usually the immunodominant antigen of the

pathogen In biology, a pathogen (, "suffering", "passion" and , "producer of"), in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a Germ theory of d ...

or a surface protein that enables the formation of neutralizing antibodies that inhibit the infection of cells. Subsequently, the protein is broken down at the

proteasome Proteasomes are essential protein complexes responsible for the degradation of proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases. Proteasomes are found inside all e ...

into short fragments (

peptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty am ...

s) that are imported into the

endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...

via the

transporter associated with antigen processing Transporter associated with antigen processing (TAP) protein complex belongs to the ATP-binding-cassette transporter family. It delivers cytosolic peptides into the endoplasmic reticulum (ER), where they bind to nascent MHC class I molecules. T ...

, allowing them to bind to MHCI-molecules that are subsequently secreted to the cell surface. The presentation of the peptides on MHC-I complexes on the cell surface is necessary for a cellular immune response. As a result, genetic vaccines and live vaccines generate

cytotoxic T-cell A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular p ...

s in addition to antibodies in the vaccinated individual. In contrast to live vaccines, only parts of the pathogen are used, which means that a reversion to an infectious pathogen cannot occur as it happened during the polio vaccinations with the Sabin vaccine.Wolfram Gerlich: ''Medizinische Virologie.'' Georg Thieme Verlag, 2010, ISBN 3131139625. S. 466.

Administration

Genetic vaccines are most commonly administered by

injection Injection or injected may refer to: Science and technology * Injective function, a mathematical function mapping distinct arguments to distinct values * Injection (medicine), insertion of liquid into the body with a syringe * Injection, in broadca ...

(intramuscular or subcutaneous) or

infusion Infusion is the process of extracting chemical compounds or flavors from plant material in a solvent such as water, oil or alcohol, by allowing the material to remain suspended in the solvent over time (a process often called steeping). An inf ...

, and less commonly and for DNA, by

gene gun In genetic engineering, a gene gun or biolistic particle delivery system is a device used to deliver exogenous DNA (transgenes), RNA, or protein to cells. By coating particles of a heavy metal with a gene of interest and firing these micro-projec ...

electroporation Electroporation, also known as electropermeabilization, is a microbiological and biotechnological technique in which an electric field is applied to cells to briefly increase the permeability of the cell membrane. The application of a high-vo ...

. While viral vectors have their own mechanisms to be taken up into cells, DNA and RNA must be introduced into cells via a method of

transfection Transfection is the process of deliberately introducing naked or purified nucleic acids into eukaryotic cells. It may also refer to other methods and cell types, although other terms are often preferred: " transformation" is typically used to des ...

. In humans, the cationic

lipid Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include storing ...

s SM-102, ALC-0159 and ALC-0315 are used in conjunction with electrically neutral helper lipids. This allows the nucleic acid to be taken up by endocytosis and then released into the cytosol.

Applications

Examples of genetic vaccines approved for use in humans include the RNA vaccines tozinameran and

mRNA-1273 The Moderna COVID19 vaccine, sold under the brand name Spikevax, is a COVID-19 vaccine developed by the American company Moderna, the United States National Institute of Allergy and Infectious Diseases (NIAID), and the Biomedical Advance ...

, the DNA vaccine ZyCoV-D as well as the viral vectors AZD1222, Ad26.COV2.S, Ad5-nCoV, and Sputnik V. In addition, genetic vaccines are being investigated against proteins of various infectious agents, protein-based

toxin A toxin is a naturally occurring poison produced by metabolic activities of living cells or organisms. They occur especially as proteins, often conjugated. The term was first used by organic chemist Ludwig Brieger (1849–1919), derived ...

s, as

cancer vaccine A cancer vaccine, or oncovaccine, is a vaccine that either treats existing cancer or prevents development of cancer. Vaccines that treat existing cancer are known as ''therapeutic'' cancer vaccines or tumor antigen vaccines. Some of the vaccines ...

s,Freda K. Stevenson, Gianfranco di Genova, Christian H. Ottensmeier, Natalia Savelyeva: ''Cancer Immunotherapy.'' Elsevier Inc., 2013, ISBN 0128059117. Kapitel IX: ''Clinical Trials of DNA vaccines''. and as tolerogenic vaccines for hyposensitization of type I

allergies Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include Allergic rhinitis, hay fever, Food allergy, food al ...

History

The first use of a viral vector for vaccination – a Modified Vaccinia Ankara Virus expressing

HBsAg HBsAg (also known as the Australia antigen) is the surface antigen of the hepatitis B virus (HBV). Its presence in blood indicates existing hepatitis B infection. Structure and function The viral envelope of an enveloped virus has different su ...

– was published by Bernard Moss and colleagues. DNA was used as a vaccine by Jeffrey Ulmer and colleagues in 1993. The first use of RNA for vaccination purposes was described in 1993 by Frédéric Martinon, Pierre Meulien and colleaguesRein Verbeke, Ine Lentacker, Stefaan C. De Smedt, Heleen Dewitte
''Three decades of messenger RNA vaccine development.''
In: ''Nano Today.'' 28, 2019, S. 100766, . and in 1994 by X. Zhou, Peter Liljeström, and colleagues in mice. Martinon demonstrated that a cellular immune response was induced by vaccination with an RNA vaccine. In 1995, Robert Conry and colleagues described that a humoral immune response was also elicited after vaccination with an RNA vaccine. While DNA vaccines were more frequently researched in the early years due to their ease of production, low cost, and high stability to degrading enzymes, but sometimes produced low vaccine responses despite containing immunostimulatory

CpG site The CpG sites or CG sites are regions of DNA where a cytosine nucleotide is followed by a guanine nucleotide in the linear sequence of bases along its 5' → 3' direction. CpG sites occur with high frequency in genomic regions called CpG isl ...

s,L. Li, N. Petrovsky: ''Molecular mechanisms for enhanced DNA vaccine immunogenicity.'' In: ''Expert review of vaccines.'' Band 15, Nummer 3, 2016, S. 313–329, , PMID 26707950, {{PMC, 4955855. more research was later conducted on RNA vaccines, whose

immunogenicity Immunogenicity is the ability of a foreign substance, such as an antigen, to provoke an immune response in the body of a human or other animal. It may be wanted or unwanted: * Wanted immunogenicity typically relates to vaccines, where the injecti ...

was often better due to inherent adjuvants and which, unlike DNA vaccines,Matthias Giese: ''Molecular Vaccines.'' Springer Science & Business Media, 2013, ISBN 3319009788. S. 497. cannot insert into the genome of the vaccinated. Accordingly, the first RNA- and DNA-based vaccines approved for humans were RNA and DNA vaccines used as COVID vaccines. Viral vectors had previously been approved as

ebola vaccine Ebola vaccines are vaccines either approved or in development to prevent Ebola. As of 2022, there are only vaccines against the Zaire ebolavirus. The first vaccine to be approved in the United States was rVSV-ZEBOV in December 2019. It had ...

References

Vaccines Nucleic acid vaccines Gene delivery