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.[1][2] 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[1][2] 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 vaccine containing whole pathogens.[1] Other advantages include being well-established technology and being suitable for immunocompromised individuals.[2] Disadvantages include being relatively complex to manufacture compared to some vaccines (such as RNA vaccine), possibly requiring adjuvants and booster shots, and requiring time to examine which antigenic combinations may work best.[2]

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.[2] An effective vaccine would elicit the immune response to the antigens and form memory that allows quick recognition of the pathogens and quick response to future infections.[1]

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.[2]

Types

Summary of subunit vaccine types[1][2]
Types Description Examples
Protein subunit contains isolated proteins from pathogens (virus or bacteria) hepatitis B, acellular pertussis vaccines
Polysaccharide contains chains of polysaccharides (sugar molecules) found in the pathogen's capsule such as cell walls of some bacteria pneumococcal polysaccharide vaccine, meningococcal vaccine preventing diseases from Neisseria meningitidis group A, C, W-135, and Y
Conjugate contains polysaccharide chains bound to carrier proteins, such as diphtheria and tetanus toxoid, to boost the immune response pneumococcal conjugate vaccine, haemophilus influenzae type b conjugate vaccine, meningococcal conjugate vaccine

Protein subunit

A protein subunit is a single protein molecule that assembles (or "coassembles") with other protein molecules to form a protein complex.

One method of production of protein-based subunits involves isolation of a specific protein from a virus and administering this by itself. A weakness of this technique is that isolated proteins can be denatured. A second method of making a subunit vaccine involves putting an antigen's gene from the targeted virus or bacterium into another virus (virus vector), yeast (yeast vector), as in the case of the hepatitis B vaccine[3] or attenuated bacterium (bacterial vector) to make a recombinant virus or bacteria to serve as the important component of a recombinant vaccine (called a recombinant subunit vaccine). The recombinant vector that is genomically modified will express the antigen. The antigen (one or more subunits of protein) is extracted from the vector.[3] Just like the highly successful subunit vaccines, the recombinant-vector-produced antigen will be of little to no risk to the patient. This is the type of vaccine currently in use for hepatitis B,[3] and it is experimentally popular, being used to try to develop new vaccines for difficult-to-vaccinate-against viruses such as ebolavirus and HIV.[4]

Polysaccharide subunit

Vi capsular polysaccharide vaccine (ViCPS) against typhoid caused by the Typhi serotype of Salmonella enterica.[5] Instead of being a protein, the Vi antigen is a bacterial capsule polysacchide, made up of a long sugar chain linked to a lipid.[6] 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.[7]

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.

Virus-like particles

Virus-like particle (VLP) vaccines use VLPs, which are proteins that mimic real virus particles.[8] They generally consist of proteins assembled into the natural shape of the virus' outer shell (capsid).

Advantages and disadvantages

Advantages

  • Cannot revert to virulence meaning they cannot cause the disease they aim to protect against[9][10]
  • Safe for immunocompromised patients[11]
  • Can withstand changes in conditions (e.g. temperature, light exposure, humidity)[9]

Disadvantages

References

  1. 1 2 3 4 5 "Module 2 - Subunit vaccines". WHO Vaccine Safety Basics e-learning course. Archived from the original on 2021-08-08.
  2. 1 2 3 4 5 6 7 "What are protein subunit vaccines and how could they be used against COVID-19?". GAVI. Archived from the original on 2021-08-17.
  3. 1 2 3 "Recombivax". Retrieved May 5, 2013.
  4. ↑ Decker JM. "Vaccines". Immunology Course 419. Department of Veterinary Science & Microbiology at The University of Arizona. Archived from the original on 2003-06-10.
  5. ↑ Raffatellu M, Chessa D, Wilson RP, Dusold R, Rubino S, Bäumler AJ (June 2005). "The Vi capsular antigen of Salmonella enterica serotype Typhi reduces Toll-like receptor-dependent interleukin-8 expression in the intestinal mucosa". Infection and Immunity. 73 (6): 3367–74. doi:10.1128/IAI.73.6.3367-3374.2005. PMC 1111811. PMID 15908363.
  6. ↑ Hu X, Chen Z, Xiong K, Wang J, Rao X, Cong Y (August 2017). "Vi capsular polysaccharide: Synthesis, virulence, and application". Critical Reviews in Microbiology. 43 (4): 440–52. doi:10.1080/1040841X.2016.1249335. PMID 27869515. S2CID 205694206.
  7. ↑ Lin FY, Ho VA, Khiem HB, Trach DD, Bay PV, Thanh TC, et al. (April 2001). "The efficacy of a Salmonella typhi Vi conjugate vaccine in two-to-five-year-old children". The New England Journal of Medicine. 344 (17): 1263–69. doi:10.1056/nejm200104263441701. PMID 11320385.
  8. ↑ Noad R, Roy P (2003-09-01). "Virus-like particles as immunogens". Trends in Microbiology. 11 (9): 438–444. doi:10.1016/S0966-842X(03)00208-7. ISSN 0966-842X. PMID 13678860.
  9. 1 2 3 4 Baxter D (December 2007). "Active and passive immunity, vaccine types, excipients and licensing". Occupational Medicine. 57 (8): 552–56. doi:10.1093/occmed/kqm110. PMID 18045976.
  10. 1 2 3 4 Moyle PM, Toth I (March 2013). "Modern subunit vaccines: development, components, and research opportunities". ChemMedChem. 8 (3): 360–76. doi:10.1002/cmdc.201200487. PMID 23316023. S2CID 205647062.
  11. 1 2 3 Vartak A, Sucheck SJ (April 2016). "Recent Advances in Subunit Vaccine Carriers". Vaccines. 4 (2): 12. doi:10.3390/vaccines4020012. PMC 4931629. PMID 27104575.
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