A subunit vaccine is a

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

that contains purified parts of the

pathogen In biology, a pathogen ( el, πάθος, "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 ...

that are antigenic, or necessary to elicit a protective

immune response An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...

. A "subunit" vaccine doesn't contain the whole pathogen, unlike live attenuated or

inactivated vaccine An inactivated vaccine (or killed vaccine) is a vaccine consisting of virus particles, bacteria, or other pathogens that have been grown in culture and then killed to destroy disease-producing capacity. In contrast, live vaccines use pathogens ...

, but contains only the antigenic parts such as proteins, polysaccharides or

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. ...

s. Because the vaccine doesn't contain "live" components of the pathogen, there is no risk of introducing the disease, and is safer and more stable than vaccine containing whole pathogens. Other advantages include being well-established technology and being suitable for

immunocompromised Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...

individuals. Disadvantages include being relatively complex to manufacture compared to some vaccines, possibly requiring

adjuvants In pharmacology, an adjuvant is a drug or other substance, or a combination of substances, that is used to increase the efficacy#Pharmacology, efficacy or Potency (pharmacology), potency of certain drugs. Specifically, the term can refer to: * Adju ...

and

booster shot A booster dose is an extra administration of a vaccine after an earlier ( primer) dose. After initial immunization, a booster provides a re-exposure to the immunizing antigen. It is intended to increase immunity against that antigen back to prote ...

s, and requiring time to examine which antigenic combinations may work best.

Mechanism

Subunit vaccines contain fragments of the pathogen, such as protein or polysaccharide, whose combinations are carefully selected to induce a strong and effective immune response. Because the immune system interacts with the pathogen in a limited way, the risk of

side effects In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

is minimal. An effective vaccine would elicit the immune response to the antigens and form

immunological memory Immunological memory is the ability of the immune system to quickly and specifically recognize an antigen that the body has previously encountered and initiate a corresponding immune response. Generally, these are secondary, tertiary and other subs ...

that allows quick recognition of the pathogens and quick response to future infections. A drawback is that the specific antigens used in a subunit vaccine may lack

pathogen-associated molecular pattern Pathogen-associated molecular patterns (PAMPs) are small molecular motifs conserved within a class of microbes. They are recognized by toll-like receptors (TLRs) and other pattern recognition receptors (PRRs) in both plants and animals. A vast arra ...

s which are common to a class of pathogen. These

molecular structure Molecular geometry is the three-dimensional arrangement of the atoms that constitute a molecule. It includes the general shape of the molecule as well as bond lengths, bond angles, torsional angles and any other geometrical parameters that deter ...

s may be used by

immune cell White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from multi ...

s for danger recognition, so without them, the immune response may be weaker. Another drawback is that the antigens do not infect cells, so the immune response to the subunit vaccines may only be antibody-mediated, not cell-mediated, and as a result, is weaker than those elicited by other types of vaccines. To increase immune response,

may be used with the subunit vaccines, or booster doses may be required.

Types

Protein subunit

A protein subunit is a

polypeptide chain Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. ...

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

molecule that assembles (or "''coassembles''") with other protein molecules to form a

protein complex A protein complex or multiprotein complex is a group of two or more associated polypeptide chains. Protein complexes are distinct from multienzyme complexes, in which multiple catalytic domains are found in a single polypeptide chain. Protein ...

. Large assemblies of proteins such as

viruses A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's ...

often use a small number of types of protein subunits as building blocks. A key step in creating a recombinant protein vaccine is the identification and isolation of a protein subunit from the pathogen which is likely to trigger a strong and effective immune response, without including the parts of the virus or bacterium that enable the pathogen to reproduce. Parts of the protein shell or

capsid A capsid is the protein shell of a virus, enclosing its genetic material. It consists of several oligomeric (repeating) structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or ma ...

of a virus are often suitable. The goal is for the protein subunit to prime the immune system response by mimicking the appearance but not the action of the pathogen. Another protein-based approach involves self‐assembly of multiple protein subunits into a

Virus-like particle Virus-like particles (VLPs) are molecules that closely resemble viruses, but are non-infectious because they contain no viral genetic material. They can be naturally occurring or synthesized through the individual expression of viral structural pro ...

(VLP) or nanoparticle. The purpose of increasing the vaccine's surface similarity to a whole virus particle (but not its ability to spread) is to trigger a stronger immune response. Protein subunit vaccines are generally made through

protein production Protein production is the biotechnological process of generating a specific protein. It is typically achieved by the manipulation of gene expression in an organism such that it expresses large amounts of a recombinant gene. This includes the t ...

, manipulating the gene expression of an organism so that it

expresses Expression may refer to: Linguistics * Expression (linguistics), a word, phrase, or sentence * Fixed expression, a form of words with a specific meaning * Idiom, a type of fixed expression * Metaphorical expression, a particular word, phrase, ...

large amounts of a

recombinant gene Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be fou ...

. A variety of approaches can be used for development depending on the vaccine involved.

Yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constit ...

baculovirus ''Baculoviridae'' is a family of viruses. Arthropods, among the most studied being Lepidoptera, Hymenoptera and Diptera, serve as natural hosts. Currently, 85 species are placed in this family, assigned to four genera. Baculoviruses are known ...

, or

mammalian Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur o ...

cell cultures can be used to produce large amounts of proteins in vitro. Protein-based vaccines are currently in use for

hepatitis B Hepatitis B is an infectious disease caused by the '' Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. ...

and for

human papillomavirus Human papillomavirus infection (HPV infection) is caused by a DNA virus from the ''Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and res ...

(HPV). The approach is being used to try to develop vaccines for difficult-to-vaccinate-against viruses such as

ebolavirus The genus ''Ebolavirus'' (- or ; - or ) is a virological taxon included in the family '' Filoviridae'' (filament-shaped viruses), order ''Mononegavirales''. The members of this genus are called ebolaviruses, and encode their genome in the for ...

and

HIV The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...

. Protein-based vaccines for COVID-19 tend to target either its spike protein or its receptor binding domain. As of 2021, the most researched vaccine platform for COVID-19 worldwide was reported to be recombinant protein subunit vaccines.

Polysaccharide subunit

Vi capsular polysaccharide vaccine (ViCPS) against

typhoid Typhoid fever, also known as typhoid, is a disease caused by ''Salmonella'' serotype Typhi bacteria. Symptoms vary from mild to severe, and usually begin six to 30 days after exposure. Often there is a gradual onset of a high fever over several d ...

caused by the Typhi serotype of ''Salmonella enterica''. Instead of being a protein, the Vi antigen is a

bacterial capsule The bacteria capsule is a large structure common to many bacteria. It is a polysaccharide layer that lies outside the cell envelope, and is thus deemed part of the outer envelope of a bacterial cell. It is a well-organized layer, not easily was ...

polysacchide, made up of a long sugar chain linked to a lipid. Capsular vaccines like ViCPS tend to be weak at eliciting immune responses in children. Making a

conjugate vaccine A conjugate vaccine is a type of subunit vaccine which combines a weak antigen with a strong antigen as a carrier so that the immune system has a stronger response to the weak antigen. Vaccines are used to prevent diseases by invoking an immune ...

by linking the polysacchide with a

toxoid A toxoid is an inactivated toxin (usually an exotoxin) whose toxicity has been suppressed either by chemical (formalin) or heat treatment, while other properties, typically immunogenicity, are maintained. Toxins are secreted by bacteria, whereas ...

increases the efficacy.

Conjugate vaccine

is a type of

which combines a weak

antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respons ...

with a strong antigen as a carrier so that the

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splint ...

has a stronger response to the weak antigen.

Peptide subunit

A peptide-based subunit vaccine employs a

instead of a full

Advantages and disadvantages

Advantages

* Cannot revert to

virulence Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ...

meaning they cannot cause the disease they aim to protect against * Safe for

patients * Can withstand changes in conditions (e.g. temperature, light exposure, humidity)

Disadvantages

* Reduced

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 injectio ...

compared to

attenuated vaccine An attenuated vaccine (or a live attenuated vaccine, LAV) is a vaccine created by reducing the virulence of a pathogen, but still keeping it viable (or "live"). Attenuation takes an infectious agent and alters it so that it becomes harmless or less ...

s ** Require

to improve immunogenicity ** Often require multiple doses ( "booster" doses) to provide long-term immunity * Can be difficult to isolate the specific antigen(s) which will invoke the necessary

References

{{Vaccines