Subunit vaccine


A subunit vaccine is a vaccine that contains purified parts of the pathogen that are antigenic, or necessary to elicit a protective immune response. Subunit vaccine can be made from dissembled viral particles in cell culture or recombinant DNA expression, in which case it is a recombinant subunit vaccine.
A "subunit" vaccine doesn't contain the whole pathogen, unlike live attenuated or inactivated vaccine, but contains only the antigenic parts such as proteins, polysaccharides or peptides. 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 vaccines containing whole pathogens.
Other advantages include being well-established technology and being suitable for immunocompromised individuals. Disadvantages include being relatively complex to manufacture compared to some vaccines, possibly requiring adjuvants and booster shots, and requiring time to examine which antigenic combinations may work best.
The first recombinant subunit vaccine was produced in the mid-1980s to protect people from Hepatitis B. Other recombinant subunit vaccines licensed include Engerix-B, Gardasil 9, Flublok, Shingrix and Nuvaxovid.
After injection, antigens trigger the production of antigen-specific antibodies, which are responsible for recognising and neutralising foreign substances. Basic components of recombinant subunit vaccines include recombinant subunits, adjuvants and carriers. Additionally, recombinant subunit vaccines are popular candidates for the development of vaccines against infectious diseases.
Recombinant subunit vaccines are considered to be safe for injection. The chances of adverse effects vary depending on the specific type of vaccine being administered. Minor side effects include injection site pain, fever, and fatigue, and serious adverse effects consist of anaphylaxis and potentially fatal allergic reaction. The contraindications are also vaccine-specific; they are generally not recommended for people with the previous history of anaphylaxis to any component of the vaccines. Advice from medical professionals should be sought before receiving any vaccination.

Discovery

The first certified subunit vaccine by clinical trials on humans is the hepatitis B vaccine, containing the surface antigens of the hepatitis B virus itself from infected patients and adjusted by newly developed technology aiming to enhance the vaccine safety and eliminate possible contamination through individuals plasma.

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 is minimal.
An effective vaccine would elicit the immune response to the antigens and form immunological memory 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 patterns which are common to a class of pathogen. These molecular structures may be used by immune cells 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, adjuvants may be used with the subunit vaccines, or booster doses may be required.

Types

Protein subunit

A protein subunit is a polypeptide chain or protein molecule that assembles with other protein molecules to form a protein complex. Large assemblies of proteins such as viruses 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 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 or nanoparticle. The purpose of increasing the vaccine's surface similarity to a whole virus particle is to trigger a stronger immune response.
Protein subunit vaccines are generally made through protein production, manipulating the gene expression of an organism so that it expresses large amounts of a recombinant gene. A variety of approaches can be used for development depending on the vaccine involved. Yeast, baculovirus, or mammalian cell cultures can be used to produce large amounts of proteins in vitro.
Protein-based vaccines are being used for hepatitis B and for human papillomavirus. The approach is being used to try to develop vaccines for difficult-to-vaccinate-against viruses such as ebolavirus and HIV. 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

against typhoid caused by the Typhi serotype of Salmonella enterica. Instead of being a protein, the Vi antigen is a bacterial capsule 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 by linking the polysacchide with a toxoid increases the efficacy.

Conjugate vaccine

A conjugate vaccine is a type of 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.

Peptide subunit

A peptide-based subunit vaccine employs a peptide instead of a full protein. Peptide-based subunit vaccine mostly used due to many reasons,such as, it is easy and affordable for massive production. Adding to that, its greatest stability, purity and exposed composition. Three steps occur leading to creation of peptide subunit vaccine;
  1. Epitope recognition
  2. Epitope optimization
  3. Peptide immunity improvement

    Features

When compared with conventional attenuated vaccines and inactivated vaccines, recombinant subunit vaccines have the following special characteristics:
  • They contain clearly identified compositions which greatly reduces the possibility of presence of undesired materials within the vaccine.
  • Their pathogenicities are minimized as only fragments of the pathogen are present in the vaccine which cannot invade and multiply within the human body.
  • They have better safety profiles and are suitable to be administered to immunocompromised patients.
  • They are suitable for mass production due to the use of recombinant technologies.
  • They have high stability so they can withstand environmental changes and are more convenient to be used in community settings.
However, there are also some drawbacks regarding recombinant subunit vaccines:
  • Addition of adjuvants is necessary during manufacturing to increase the efficacy of these vaccines.
  • Patients will have to receive booster doses to maintain long-term immunity.
  • Selection of appropriate cell lines for the cultivation of subunits is time-consuming because microbial proteins can be incompatible to certain expression systems.

    Pharmacology

is a potent way to protect individuals against infectious diseases.
Active immunity can be acquired artificially by vaccination as a result of the body's own defense mechanism being triggered by the exposure of a small, controlled amount of pathogenic substances to produce its own antibodies and memory cells without being infected by the real pathogen.
The processes involved in primary immune response are as follows:
  1. Pre-exposure to the antigens present in vaccines elicits a primary response. After injection, antigens will be ingested by antigen-presenting cells, such as dendritic cells and macrophages, via phagocytosis.
  2. The APCs will travel to lymph nodes, where immature B cells and T cells are present.
  3. Following antigen processes by APCs, antigens will bind to either MHC class I receptors or MHC class II receptors on the cell surface of the cells based on their compositional and structural features to form complexes.
  4. Antigen presentation occurs, in which T cell receptors attach to the antigen-MHC complexes, initiating clonal expansion and differentiation, and hence the conversion of naive T cells to cytotoxic T cells or helper T cells.
  5. Cytotoxic CD8+ cells can directly destroy the infected cells containing the antigens that were presented to them by the APCs by releasing lytic molecules, while helper CD4+ cells are responsible for the secretion of cytokines that activates B cells and cytotoxic T cells.
  6. B cells can undergo activation in the absence of T cells via the B cell receptor signalling pathway.
  7. After dendritic cells capture the immunogen present in the vaccine, they can present the substances to naive B cells, causing the proliferation of plasma cells for antibody production. Isotype switching can take place during B cell development for the formation of different antibodies, including IgG, IgE and IgA.
  8. Memory B cells and T cells are formed post-infection. The antigens are memorised by these cells so that subsequent exposure to the same type of antigens will stimulate a secondary response, in which a higher concentration of antibodies specific for the antigens are reproduced rapidly and efficiently in a short time for the elimination of the pathogen.
Under specific circumstances, low doses of vaccines are given initially, followed by additional doses named booster doses. Boosters can effectively maintain the level of memory cells in the human body, hence extending a person's immunity.