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.[3] 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, possibly requiring adjuvants and booster shots, and requiring time to examine which antigenic combinations may work best.[2]

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.[4]

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 immunological 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 polypeptide chain or protein molecule that assembles (or "coassembles") with other protein molecules to form a protein complex.[5][6][7] Large assemblies of proteins such as viruses often use a small number of types of protein subunits as building blocks.[8] 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.[9] Another protein-based approach involves self‐assembly of multiple protein subunits into a Virus-like particle (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.[10][9][11]

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.[9][12] A variety of approaches can be used for development depending on the vaccine involved.[10] Yeast, baculovirus, or mammalian cell cultures can be used to produce large amounts of proteins in vitro.[9][12][13]

Protein-based vaccines are currently in use for hepatitis B and for human papillomavirus (HPV).[10][9] The approach is being used to try to develop vaccines for difficult-to-vaccinate-against viruses such as ebolavirus and HIV.[14] Protein-based vaccines for COVID-19 tend to target either its spike protein or its receptor binding domain.[10] As of 2021, the most researched vaccine platform for COVID-19 worldwide was reported to be recombinant protein subunit vaccines.[9]

Polysaccharide subunit

Vi capsular polysaccharide vaccine (ViCPS) against typhoid caused by the Typhi serotype of Salmonella enterica.[15] Instead of being a protein, the Vi antigen is a bacterial capsule polysacchide, made up of a long sugar chain linked to a lipid.[16] 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.[17]

Conjugate vaccine

Main article: 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.[18]

Peptide subunit

A peptide-based subunit vaccine employs a peptide instead of a full protein.[19] 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.[20] Three steps occur leading to creation of peptide subunit vaccine;[21]

  1. Epitope recognition
  2. Epitope optimization
  3. Peptide immunity improvement

Advantages and disadvantages

Advantages

  • Cannot revert to virulence meaning they cannot cause the disease they aim to protect against[22][23]
  • Safe for immunocompromised patients[24]
  • Can withstand changes in conditions (e.g. temperature, light exposure, humidity)[22]

Disadvantages

Future directions

Along with technology development, investigators are now able to reach a great control and supervision over parameters of multiple variations to decrease toxicity, to improve immunogenicity and stability of antigen. Furthermore, subunit vaccines are not only considered effective for SARS-COV-2, also candidates for evolving immunizations against Malaria, Tetanus, Salmonella Enterica and many other diseases in the future.[4]

References

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  2. ^ a b c d e f g "What are protein subunit vaccines and how could they be used against COVID-19?". GAVI. Archived from the original on 2021-08-17.
  3. ^ Lidder P, Sonnino A (2012). "Biotechnologies for the management of genetic resources for food and agriculture". Advances in Genetics. Elsevier. 78: 1–167. doi:10.1016/B978-0-12-394394-1.00001-8. PMID 22980921.
  4. ^ a b Cuffari B (2022). "What is a Subunit Vaccine?". News medical lifesciences.
  5. ^ Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002). The Shape and Structure of Proteins. New York: Garland Science. Retrieved 15 April 2022.
  6. ^ Stoker HS (1 January 2015). General, Organic, and Biological Chemistry (7th ed.). Boston, MA: Cengage Learning. pp. 709–710. ISBN 978-1-305-68618-2. Retrieved 15 April 2022.
  7. ^ Smith MB (27 April 2020). Biochemistry: An Organic Chemistry Approach. Boca Raton: CRC Press. p. 269-270. ISBN 978-1-351-25807-4. Retrieved 15 April 2022.
  8. ^ Vijayan M, Yathindra N, Kolaskar AS (1999). "Multi-protein assemblies with point group symmetry". In Vijayan M, Yathindra N, Kolaskar AS (eds.). Perspectives in Structural Biology: A Volume in Honour of G.N. Ramachandran. Hyderabad, India: Universities Press. pp. 449–466. ISBN 978-81-7371-254-8. Retrieved 15 April 2022.
  9. ^ a b c d e f Plummer EM, Manchester M (2011). "Viral nanoparticles and virus-like particles: platforms for contemporary vaccine design". Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology. 3 (2): 174–196. doi:10.1002/wnan.119. PMC 7169818. PMID 20872839.
  10. ^ a b c d Hotez PJ, Bottazzi ME (January 2022). "Whole Inactivated Virus and Protein-Based COVID-19 Vaccines". Annual Review of Medicine. 73 (1): 55–64. doi:10.1146/annurev-med-042420-113212. PMID 34637324. S2CID 238747462.
  11. ^ Noad R, Roy P (September 2003). "Virus-like particles as immunogens". Trends in Microbiology. 11 (9): 438–444. doi:10.1016/S0966-842X(03)00208-7. PMID 13678860.
  12. ^ a b Wang M, Jiang S, Wang Y (April 2016). "Recent advances in the production of recombinant subunit vaccines in Pichia pastoris". Bioengineered. 7 (3): 155–165. doi:10.1080/21655979.2016.1191707. PMC 4927204. PMID 27246656.
  13. ^ Bill RM (March 2015). "Recombinant protein subunit vaccine synthesis in microbes: a role for yeast?". The Journal of Pharmacy and Pharmacology. 67 (3): 319–328. doi:10.1111/jphp.12353. PMID 25556638. S2CID 22339760.
  14. ^ Decker JM. "Vaccines". Immunology Course 419. Department of Veterinary Science & Microbiology at The University of Arizona. Archived from the original on 2003-06-10.
  15. ^ 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): 3367–3374. doi:10.1128/IAI.73.6.3367-3374.2005. PMC 1111811. PMID 15908363.
  16. ^ 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): 440–452. doi:10.1080/1040841X.2016.1249335. PMID 27869515. S2CID 205694206.
  17. ^ 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): 1263–1269. doi:10.1056/nejm200104263441701. PMID 11320385.
  18. ^ Pollard A. "Types of vaccine". Oxford vaccine group 2020. University of Oxford.
  19. ^ Malonis RJ, Lai JR, Vergnolle O (March 2020). "Peptide-Based Vaccines: Current Progress and Future Challenges". Chemical Reviews. PubMed Central. 120 (6): 3210–3229. doi:10.1021/acs.chemrev.9b00472. PMC 7094793. PMID 31804810.
  20. ^ Skwarczynski M, Toth I (May 2011). "Peptide-based subunit nanovaccines". Current Drug Delivery. 8 (3): 282–289. doi:10.2174/156720111795256192. PMID 21291373.
  21. ^ Kalita P, Tripathi T (May 2022). "Methodological advances in the design of peptide-based vaccines". Drug Discovery Today. Elsevier. 27 (5): 1367–1380. doi:10.1016/j.drudis.2022.03.004. PMID 35278703.
  22. ^ a b c d Baxter D (December 2007). "Active and passive immunity, vaccine types, excipients and licensing". Occupational Medicine. 57 (8): 552–556. doi:10.1093/occmed/kqm110. PMID 18045976.
  23. ^ a b c d Moyle PM, Toth I (March 2013). "Modern subunit vaccines: development, components, and research opportunities". ChemMedChem. 8 (3): 360–376. doi:10.1002/cmdc.201200487. PMID 23316023. S2CID 205647062.
  24. ^ a b c d Vartak A, Sucheck SJ (April 2016). "Recent Advances in Subunit Vaccine Carriers". Vaccines. 4 (2): 12. doi:10.3390/vaccines4020012. PMC 4931629. PMID 27104575.