subunit vaccine

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.{{cite news |vauthors=Cuffari B |title=What is a Subunit Vaccine? |url=https://www.news-medical.net/health/What-is-a-Subunit-Vaccine.aspx |publisher=News medical lifesciences |date=2022 |access-date=2023-01-12 |archive-date=2022-05-25 |archive-url=https://web.archive.org/web/20220525050646/https://www.news-medical.net/health/What-is-a-Subunit-Vaccine.aspx |url-status=live }}

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.

{{anchor | Protein}}

A protein subunit is a polypeptide chain or protein molecule that assembles (or "coassembles") with other protein molecules to form a protein complex.{{cite book |vauthors=Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P |title=The Shape and Structure of Proteins |date=2002 |publisher=Garland Science |location=New York |url=https://www.ncbi.nlm.nih.gov/books/NBK26830/ |access-date=15 April 2022 |language=en |archive-date=26 March 2020 |archive-url=https://web.archive.org/web/20200326072955/https://www.ncbi.nlm.nih.gov/books/NBK26830/ |url-status=live }}{{cite book |vauthors=Stoker HS |title=General, Organic, and Biological Chemistry |date=1 January 2015 |publisher=Cengage Learning |location=Boston, MA |isbn=978-1-305-68618-2 |pages=709–710 |edition=7th |url=https://books.google.com/books?id=IBGdBQAAQBAJ&pg=PA709 |access-date=15 April 2022 |language=en |archive-date=5 September 2023 |archive-url=https://web.archive.org/web/20230905200413/https://books.google.com/books?id=IBGdBQAAQBAJ&pg=PA709 |url-status=live }}{{cite book |vauthors=Smith MB |title=Biochemistry: An Organic Chemistry Approach |date=27 April 2020 |publisher=CRC Press |location=Boca Raton |isbn=978-1-351-25807-4 |pages=269–270 |url=https://books.google.com/books?id=0TXfDwAAQBAJ&pg=PA269 |access-date=15 April 2022 |language=en |archive-date=5 September 2023 |archive-url=https://web.archive.org/web/20230905200447/https://books.google.com/books?id=0TXfDwAAQBAJ&pg=PA269 |url-status=live }} Large assemblies of proteins such as viruses often use a small number of types of protein subunits as building blocks.{{cite book |vauthors=Vijayan M, Yathindra N, Kolaskar AS |chapter=Multi-protein assemblies with point group symmetry |veditors=Vijayan M, Yathindra N, Kolaskar AS |title=Perspectives in Structural Biology: A Volume in Honour of G.N. Ramachandran |date=1999 |publisher=Universities Press |location=Hyderabad, India |isbn=978-81-7371-254-8 |pages=449–466 |chapter-url=https://books.google.com/books?id=xTy_M3B5sf4C&pg=PA462 |access-date=15 April 2022 |language=en |archive-date=8 November 2023 |archive-url=https://web.archive.org/web/20231108052454/https://books.google.com/books?id=xTy_M3B5sf4C&pg=PA462#v=onepage&q&f=false |url-status=live }} 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.{{cite journal | vauthors = Plummer EM, Manchester M | title = Viral nanoparticles and virus-like particles: platforms for contemporary vaccine design | journal = Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology | volume = 3 | issue = 2 | pages = 174–196 | date = 2011 | pmid = 20872839 | pmc = 7169818 | doi = 10.1002/wnan.119 }} 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.{{cite journal | vauthors = Noad R, Roy P | title = Virus-like particles as immunogens | journal = Trends in Microbiology | volume = 11 | issue = 9 | pages = 438–444 | date = September 2003 | pmid = 13678860 | doi = 10.1016/S0966-842X(03)00208-7 }}

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.{{cite journal | vauthors = Wang M, Jiang S, Wang Y | title = Recent advances in the production of recombinant subunit vaccines in Pichia pastoris | journal = Bioengineered | volume = 7 | issue = 3 | pages = 155–165 | date = April 2016 | pmid = 27246656 | pmc = 4927204 | doi = 10.1080/21655979.2016.1191707 }}{{cite journal | vauthors = Bill RM | title = Recombinant protein subunit vaccine synthesis in microbes: a role for yeast? | journal = The Journal of Pharmacy and Pharmacology | volume = 67 | issue = 3 | pages = 319–328 | date = March 2015 | pmid = 25556638 | doi = 10.1111/jphp.12353 | s2cid = 22339760 | doi-access = free }}

Protein-based vaccines are being used for hepatitis B and for human papillomavirus (HPV). The approach is being used to try to develop vaccines for difficult-to-vaccinate-against viruses such as ebolavirus and HIV.{{cite web | title = Vaccines | vauthors = Decker JM | url = http://microvet.arizona.edu/courses/mic419/Tutorials/vaccines.html | work = Immunology Course 419 | publisher = Department of Veterinary Science & Microbiology at The University of Arizona | archive-url = https://web.archive.org/web/20030610062512/http://microvet.arizona.edu/Courses/MIC419/Tutorials/vaccines.html | archive-date=2003-06-10 }} Protein-based vaccines for COVID-19 tend to target either its spike protein or its receptor binding domain.{{cite journal | vauthors = Hotez PJ, Bottazzi ME | title = Whole Inactivated Virus and Protein-Based COVID-19 Vaccines | journal = Annual Review of Medicine | volume = 73 | issue = 1 | pages = 55–64 | date = January 2022 | pmid = 34637324 | doi = 10.1146/annurev-med-042420-113212 | s2cid = 238747462 | doi-access = free }} As of 2021, the most researched vaccine platform for COVID-19 worldwide was reported to be recombinant protein subunit vaccines.{{cite journal | vauthors = Bayani F, Hashkavaei NS, Arjmand S, Rezaei S, Uskoković V, Alijanianzadeh M, Uversky VN, Ranaei Siadat SO, Mozaffari-Jovin S, Sefidbakht Y | display-authors = 6 | title = An overview of the vaccine platforms to combat COVID-19 with a focus on the subunit vaccines | journal = Progress in Biophysics and Molecular Biology | volume = 178 | pages = 32–49 | date = March 2023 | pmid = 36801471 | pmc = 9938630 | doi = 10.1016/j.pbiomolbio.2023.02.004 }}

{{anchor | Polysaccharide}}

Vi capsular polysaccharide vaccine (ViCPS) against typhoid caused by the Typhi serotype of Salmonella enterica.{{cite journal | vauthors = Raffatellu M, Chessa D, Wilson RP, Dusold R, Rubino S, Bäumler AJ | title = The Vi capsular antigen of Salmonella enterica serotype Typhi reduces Toll-like receptor-dependent interleukin-8 expression in the intestinal mucosa | journal = Infection and Immunity | volume = 73 | issue = 6 | pages = 3367–3374 | date = June 2005 | pmid = 15908363 | pmc = 1111811 | doi = 10.1128/IAI.73.6.3367-3374.2005 }} Instead of being a protein, the Vi antigen is a bacterial capsule polysacchide, made up of a long sugar chain linked to a lipid.{{cite journal | vauthors = Hu X, Chen Z, Xiong K, Wang J, Rao X, Cong Y | title = Vi capsular polysaccharide: Synthesis, virulence, and application | journal = Critical Reviews in Microbiology | volume = 43 | issue = 4 | pages = 440–452 | date = August 2017 | pmid = 27869515 | doi = 10.1080/1040841X.2016.1249335 | s2cid = 205694206 }} 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.{{cite journal | vauthors = Lin FY, Ho VA, Khiem HB, Trach DD, Bay PV, Thanh TC, Kossaczka Z, Bryla DA, Shiloach J, Robbins JB, Schneerson R, Szu SC | display-authors = 6 | title = The efficacy of a Salmonella typhi Vi conjugate vaccine in two-to-five-year-old children | journal = The New England Journal of Medicine | volume = 344 | issue = 17 | pages = 1263–1269 | date = April 2001 | pmid = 11320385 | doi = 10.1056/nejm200104263441701 | doi-access = free }}

{{anchor | Conjugate}}

{{main|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.{{cite web |vauthors=Pollard A |title=Types of vaccine |url=https://vk.ovg.ox.ac.uk/vk/types-of-vaccine |website=Oxford vaccine group 2020 |publisher=University of Oxford |access-date=2023-01-12 |archive-date=2021-11-16 |archive-url=https://web.archive.org/web/20211116043518/https://vk.ovg.ox.ac.uk/vk/types-of-vaccine |url-status=live }}

A peptide-based subunit vaccine employs a peptide instead of a full protein.{{cite journal | vauthors = Malonis RJ, Lai JR, Vergnolle O | title = Peptide-Based Vaccines: Current Progress and Future Challenges | journal = Chemical Reviews | volume = 120 | issue = 6 | pages = 3210–3229 | date = March 2020 | pmid = 31804810 | pmc = 7094793 | doi = 10.1021/acs.chemrev.9b00472 }} 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.{{cite journal | vauthors = Skwarczynski M, Toth I | title = Peptide-based subunit nanovaccines | journal = Current Drug Delivery | volume = 8 | issue = 3 | pages = 282–289 | date = May 2011 | pmid = 21291373 | doi = 10.2174/156720111795256192 }} Three steps occur leading to creation of peptide subunit vaccine;{{cite journal | vauthors = Kalita P, Tripathi T | title = Methodological advances in the design of peptide-based vaccines | journal = Drug Discovery Today | volume = 27 | issue = 5 | pages = 1367–1380 | date = May 2022 | pmid = 35278703 | doi = 10.1016/j.drudis.2022.03.004 | publisher = Elsevier | s2cid = 247399368 }}

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

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.{{citation needed|date=June 2024}}
• Their pathogenicities are minimized as only fragments of the pathogen are present in the vaccine which cannot invade and multiply within the human body.{{cite journal | vauthors = Baxter D | title = Active and passive immunity, vaccine types, excipients and licensing | journal = Occupational Medicine | volume = 57 | issue = 8 | pages = 552–556 | date = December 2007 | pmid = 18045976 | doi = 10.1093/occmed/kqm110 | doi-access = free }}
• They have better safety profiles{{cite journal | vauthors = Nascimento IP, Leite LC | title = Recombinant vaccines and the development of new vaccine strategies | journal = Brazilian Journal of Medical and Biological Research | volume = 45 | issue = 12 | pages = 1102–1111 | date = December 2012 | pmid = 22948379 | pmc = 3854212 | doi = 10.1590/S0100-879X2012007500142 }} and are suitable to be administered to immunocompromised patients.
• They are suitable for mass production due to the use of recombinant technologies.{{citation needed|date=June 2024}}
• 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.{{cite journal | vauthors = Sedova ES, Shcherbinin DN, Migunov AI, Smirnov I, Logunov DI, Shmarov MM, Tsybalova LM, Naroditskiĭ BS, Kiselev OI, Gintsburg AL | display-authors = 6 | title = Recombinant influenza vaccines | journal = Acta Naturae | volume = 4 | issue = 4 | pages = 17–27 | date = October 2012 | doi = 10.32607/20758251-2012-4-4-17-27 | pmid = 23346377 | pmc = 3548171 }}
• Patients will have to receive booster doses to maintain long-term immunity.{{Cite book | vauthors = Andersson C |url=http://worldcat.org/oclc/1301470908 |title=Production and delivery of recombinant subunit vaccines |oclc=1301470908}}
• Selection of appropriate cell lines for the cultivation of subunits is time-consuming because microbial proteins can be incompatible to certain expression systems.

File:Primary immune response 1.png

Vaccination is a potent way to protect individuals against infectious diseases.{{cite journal | vauthors = Rodrigues CM, Plotkin SA | title = Impact of Vaccines; Health, Economic and Social Perspectives | journal = Frontiers in Microbiology | volume = 11 | pages = 1526 | date = 2020-07-14 | pmid = 32760367 | pmc = 7371956 | doi = 10.3389/fmicb.2020.01526 | doi-access = free }}

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.{{cite journal | vauthors = Clem AS | title = Fundamentals of vaccine immunology | journal = Journal of Global Infectious Diseases | volume = 3 | issue = 1 | pages = 73–78 | date = January 2011 | pmid = 21572612 | pmc = 3068582 | doi = 10.4103/0974-777X.77299 | doi-access = free }}

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 (APCs), 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.{{cite journal | vauthors = LeBien TW, Tedder TF | title = B lymphocytes: how they develop and function | journal = Blood | volume = 112 | issue = 5 | pages = 1570–1580 | date = September 2008 | pmid = 18725575 | doi = 10.1182/blood-2008-02-078071 | pmc = 2518873 }}
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 (CD8+) or helper T cells (CD4+).{{cite journal | vauthors = Kallon S, Samir S, Goonetilleke N | title = Vaccines: Underlying Principles of Design and Testing | journal = Clinical Pharmacology and Therapeutics | volume = 109 | issue = 4 | pages = 987–999 | date = April 2021 | pmid = 33705574 | pmc = 8048882 | doi = 10.1002/cpt.2207 }}{{cite journal | vauthors = Curtsinger JM, Johnson CM, Mescher MF | title = CD8 T cell clonal expansion and development of effector function require prolonged exposure to antigen, costimulation, and signal 3 cytokine | journal = Journal of Immunology | volume = 171 | issue = 10 | pages = 5165–5171 | date = November 2003 | pmid = 14607916 | doi = 10.4049/jimmunol.171.10.5165 | s2cid = 24326081 | doi-access = free }}
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.{{cite journal | vauthors = Klarquist J, Cross EW, Thompson SB, Willett B, Aldridge DL, Caffrey-Carr AK, Xu Z, Hunter CA, Getahun A, Kedl RM | display-authors = 6 | title = B cells promote CD8 T cell primary and memory responses to subunit vaccines | journal = Cell Reports | volume = 36 | issue = 8 | pages = 109591 | date = August 2021 | pmid = 34433030 | pmc = 8456706 | doi = 10.1016/j.celrep.2021.109591 }}
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.{{cite journal | vauthors = Wykes M, MacPherson G | title = Dendritic cell-B-cell interaction: dendritic cells provide B cells with CD40-independent proliferation signals and CD40-dependent survival signals | journal = Immunology | volume = 100 | issue = 1 | pages = 1–3 | date = May 2000 | pmid = 10809952 | pmc = 2326988 | doi = 10.1046/j.1365-2567.2000.00044.x }} Isotype switching can take place during B cell development for the formation of different antibodies, including IgG, IgE and IgA.{{cite journal | vauthors = Saylor K, Gillam F, Lohneis T, Zhang C | title = Designs of Antigen Structure and Composition for Improved Protein-Based Vaccine Efficacy | journal = Frontiers in Immunology | volume = 11 | issue = 283 | pages = 283 | date = 24 February 2020 | pmid = 32153587 | pmc = 7050619 | doi = 10.3389/fimmu.2020.00283 | doi-access = free }}
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.{{cite journal | vauthors = Meng H, Mao J, Ye Q | title = Booster vaccination strategy: Necessity, immunization objectives, immunization strategy, and safety | journal = Journal of Medical Virology | volume = 94 | issue = 6 | pages = 2369–2375 | date = June 2022 | pmid = 35028946 | doi = 10.1002/jmv.27590 | s2cid = 245933504 }}

The manufacturing process of recombinant subunit vaccines are as follows:{{citation needed|date=May 2024}}

1. Identification of immunogenic subunit
2. Subunit expression and synthesis
3. Extraction and purification
4. Addition of adjuvants or incorporation to vectors
5. Formulation and delivery.

Candidate subunits will be selected primarily by their immunogenicity.{{cite journal | vauthors = Lindskog M, Rockberg J, Uhlén M, Sterky F | title = Selection of protein epitopes for antibody production | journal = BioTechniques | volume = 38 | issue = 5 | pages = 723–727 | date = May 2005 | pmid = 15945371 | doi = 10.2144/05385ST02 | doi-access = free }} To be immunogenic, they should be of foreign nature and of sufficient complexity for the reaction between different components of the immune system and the candidates to occur.{{cite book | chapter = Chapter 4 The nature of immunogens, antigens, and haptens |date=1985-01-01 | doi = 10.1016/S0075-7535(08)70134-7 | title = Laboratory Techniques in Biochemistry and Molecular Biology |volume=15 |pages=39–41 | veditors = Tijssen P |series=Practice and Theory of Enzyme Immunoassays |publisher=Elsevier |isbn=9780444806345 |language=en }} Candidates are also selected based on size, nature of function (e.g. signalling) and cellular location (e.g. transmembrane).

Upon identifying the target subunit and its encoding gene, the gene will be isolated and transferred to a second, non-pathogenic organism, and cultured for mass production. The process is also known as heterologous expression.{{citation needed|date=May 2024}}

A suitable expression system is selected based on the requirement of post-translational modifications, costs, ease of product extraction and production efficiency. Commonly used systems for both licensed and developing recombinant subunit vaccines include bacteria, yeast, mammalian cells, insect cells.{{cite journal | vauthors = Francis MJ | title = Recent Advances in Vaccine Technologies | journal = The Veterinary Clinics of North America. Small Animal Practice | volume = 48 | issue = 2 | pages = 231–241 | date = March 2018 | pmid = 29217317 | pmc = 7132473 | doi = 10.1016/j.cvsm.2017.10.002 }}

File:E. coli Bacteria (7316101966).jpg

Bacterial cells are widely used for cloning processes, genetic modification and small-scale productions.{{cite journal | vauthors = Ferrer-Miralles N, Domingo-Espín J, Corchero JL, Vázquez E, Villaverde A | title = Microbial factories for recombinant pharmaceuticals | journal = Microbial Cell Factories | volume = 8 | issue = 1 | pages = 17 | date = March 2009 | pmid = 19317892 | doi = 10.1186/1475-2859-8-17 | pmc = 2669800 | doi-access = free }} Escherichia coli (E. Coli) is widely utilised due to its highly explored genetics, widely available genetic tools for gene expression, accurate profiling and its ability to grow in inexpensive media at high cell densities.{{cite journal | vauthors = Corchero JL, Gasser B, Resina D, Smith W, Parrilli E, Vázquez F, Abasolo I, Giuliani M, Jäntti J, Ferrer P, Saloheimo M, Mattanovich D, Schwartz S, Tutino ML, Villaverde A | display-authors = 6 | title = Unconventional microbial systems for the cost-efficient production of high-quality protein therapeutics | journal = Biotechnology Advances | volume = 31 | issue = 2 | pages = 140–153 | date = 2013 | pmid = 22985698 | doi = 10.1016/j.biotechadv.2012.09.001 }}

E. Coli is mostly appropriate for structurally simple proteins owing to its inability to carry out post-translational modifications, lack of protein secretary system and the potential for producing inclusion bodies that require additional solubilisation.{{cite journal | vauthors = Taguchi S, Ooi T, Mizuno K, Matsusaki H | title = Advances and needs for endotoxin-free production strains | journal = Applied Microbiology and Biotechnology | volume = 99 | issue = 22 | pages = 9349–9360 | date = November 2015 | pmid = 26362682 | doi = 10.1007/s00253-015-6947-9 | s2cid = 8308134 }} Regarding application, E.Coli is being utilised as the expression system of the dengue vaccine.{{cite journal | vauthors = Tripathi NK, Shrivastava A | title = Recent Developments in Recombinant Protein-Based Dengue Vaccines | journal = Frontiers in Immunology | volume = 9 | pages = 1919 | date = 2018-08-23 | pmid = 30190720 | pmc = 6115509 | doi = 10.3389/fimmu.2018.01919 | doi-access = free }}

Yeast matches bacterial cells' cost-effectiveness, efficiency and technical feasibility. Moreover, yeast secretes soluble proteins and has the ability to perform post-translational modifications similar to mammalian cells.

File:Saccharomyces cerevisiae YGC colonies 50.jpg

Notably, yeast incorporates more mannose molecules during N-glycosylation when compared with other eukaryotes,{{cite journal | vauthors = Gerngross TU | title = Advances in the production of human therapeutic proteins in yeasts and filamentous fungi | journal = Nature Biotechnology | volume = 22 | issue = 11 | pages = 1409–1414 | date = November 2004 | pmid = 15529166 | doi = 10.1038/nbt1028 | s2cid = 22230030 }} which may trigger cellular conformational stress responses. Such responses may result in failure in reaching native protein conformation, implying potential reduction of serum half-life and immunogenicity. Regarding application, both the hepatitis B virus surface antigen (HBsAg) and the virus-like particles (VLPs) of the major capsid protein L1 of human papillomavirus type 6, 11, 16, 18 are produced by Saccharomyces cerevisiae.{{citation needed|date=May 2024}}

Mammalian cells are well known for their ability to perform therapeutically essential post-translational modifications and express properly folded, glycosylated and functionally active proteins.{{cite journal | vauthors = Zhu J | title = Mammalian cell protein expression for biopharmaceutical production | journal = Biotechnology Advances | volume = 30 | issue = 5 | pages = 1158–1170 | date = 2012 | pmid = 21968146 | doi = 10.1016/j.biotechadv.2011.08.022 }}{{cite journal | vauthors = Baeshen NA, Baeshen MN, Sheikh A, Bora RS, Ahmed MM, Ramadan HA, Saini KS, Redwan EM | display-authors = 6 | title = Cell factories for insulin production | journal = Microbial Cell Factories | volume = 13 | issue = 1 | pages = 141 | date = October 2014 | pmid = 25270715 | doi = 10.1186/s12934-014-0141-0 | pmc = 4203937 | doi-access = free }} However, efficacy of mammalian cells may be limited by epigenetic gene silencing and aggresome formation (recombinant protein aggregation). For mammalian cells, synthesised proteins were reported to be secreted into chemically defined media, potentially simplifying protein extraction and purification.

The most prominent example under this class is Chinese Hamster Ovary (CHO) cells utilised for the synthesis of recombinant varicella zoster virus surface glycoprotein (gE) antigen for SHINGRIX. CHO cells are recognised for rapid growth and their ability to offer process versatility. They can also be cultured in suspension-adapted culture in protein-free medium, hence reducing risk of prion-induced contamination.

File:Fmicb-08-01337-g001.jpg

The baculovirus-insect cell expression system has the ability to express a variety of recombinant proteins at high levels and provide significant eukaryotic protein processing capabilities, including phosphorylation, glycosylation, myristoylation and palmitoylation.{{cite book | vauthors = Jarvis DL | title = Guide to Protein Purification, 2nd Edition | chapter = Chapter 14 Baculovirus–Insect Cell Expression Systems | series = Methods in Enzymology | volume = 463 | pages = 191–222 | date = 2009 | pmid = 19892174 | doi = 10.1016/s0076-6879(09)63014-7 | publisher = Elsevier | isbn = 9780123745361 }} Similar to mammalian cells, proteins expressed are mostly soluble, accurately folded, and biologically active.{{cite book | vauthors = Galleno M, Sick AJ | chapter = Baculovirus expression vector system |date=1999 | title = Gene Expression Systems |pages=331–363 |publisher=Elsevier }} However, it has slower growth rate and requires higher cost of growth medium than bacteria and yeast, and confers toxicological risks. A notable feature is the existence of elements of control that allow for the expression of secreted and membrane-bound proteins in Baculovirus-insect cells.

Licensed recombinant subunit vaccines that utilises baculovirus-insect cells include Cervarix (papillomavirus C-terminal truncated major capsid protein L1 types 16 and 18) and Flublok Quadrivalent (hemagglutinin (HA) proteins from four strains of influenza viruses).

Throughout history, extraction and purification methods have evolved from standard chromatographic methods to the utilisation of affinity tags.{{cite journal | vauthors = Wingfield PT | title = Overview of the purification of recombinant proteins | journal = Current Protocols in Protein Science | volume = 80 | issue = 1 | pages = 6.1.1–6.1.35 | date = April 2015 | pmid = 25829302 | doi = 10.1002/0471140864.ps0601s80 | pmc = 4410719 }} However, the final extraction and purification process undertaken highly depends on the chosen expression system. Please refer to subunit expression and synthesis for more insights.{{citation needed|date=May 2024}}

Adjuvants are materials added to improve immunogenicity of recombinant subunit vaccines.{{cite book | vauthors = Shah RR | chapter = Overview of Vaccine Adjuvants: Introduction, History, and Current Status |date=2017 | title = Vaccine Adjuvants | series = Methods in Molecular Biology |volume=1494 |pages=1–13 | veditors = Fox CB, Hassett KJ, Brito LA | place=New York, NY |publisher=Springer New York |language=en |doi=10.1007/978-1-4939-6445-1_1 | pmid = 27718182 |isbn=978-1-4939-6443-7 }}

Adjuvants increase the magnitude of adaptive response to the vaccine and guide the activation of the most effective forms of immunity for each specific pathogen (e.g. increasing generation of T cell memory).{{cite journal | vauthors = Coffman RL, Sher A, Seder RA | title = Vaccine adjuvants: putting innate immunity to work | journal = Immunity | volume = 33 | issue = 4 | pages = 492–503 | date = October 2010 | pmid = 21029960 | pmc = 3420356 | doi = 10.1016/j.immuni.2010.10.002 }}{{cite journal | vauthors = Soler E, Houdebine LM | title = Preparation of recombinant vaccines | journal = Biotechnology Annual Review | volume = 13 | pages = 65–94 | date = 2007 | pmid = 17875474 | pmc = 7106376 | doi = 10.1016/s1387-2656(07)13004-0 | publisher = Elsevier | isbn = 978-0-444-53032-5 }}{{Cite journal | vauthors = Rambe DS, Del Giudice G, Rossi S, Sanicas M |date=2015-07-06 |title=Safety and Mechanism of Action of Licensed Vaccine Adjuvants |journal=International Current Pharmaceutical Journal |volume=4 |issue=8 |pages=420–431 |doi=10.3329/icpj.v4i8.24024 |issn=2224-9486|doi-access=free }} Addition of adjuvants may confer benefits including dose sparing and stabilisation of final vaccine formulation.

Appropriate adjuvants are chosen based on safety, tolerance, compatibility of antigen and manufacturing considerations. Commonly used adjuvants for recombinant subunit vaccines are Alum adjuvants (e.g. aluminium hydroxide), Emulsions (e.g. MF59) and Liposomes combined with immunostimulatory molecules (e.g. AS01_B).

Delivery systems are primarily divided into polymer-based delivery systems (microspheres and liposomes) and live delivery systems (gram-positive bacteria, gram-negative bacteria and viruses){{citation needed|date=May 2024}}

Vaccine antigens are often encapsulated within microspheres or liposomes. Common microspheres made using Poly-lactic acid (PLA){{Cite journal | vauthors = Qi F, Wu J, Li H, Ma G |date=2018-06-09 |title=Recent research and development of PLGA/PLA microspheres/nanoparticles: A review in scientific and industrial aspects |journal=Frontiers of Chemical Science and Engineering |volume=13 |issue=1 |pages=14–27 |doi=10.1007/s11705-018-1729-4 |s2cid=103993541 |issn=2095-0179}} and poly-lactic-co-glycolic acid (PLGA) allow for controlled antigen release by degrading in vivo while liposomes including multilamellar or unilamellar vesicles allow for prolonged release.

Polymer-based delivery systems confer advantages such as increased resistance to degradation in GI tract, controlled antigen release, raised particle uptake by immune cells and enhanced ability to induce cytotoxic T cell responses. An example of licensed recombinant vaccine utilising liposomal delivery is Shringrix.

Live delivery systems, also known as vectors, are cells modified with ligands or antigens to improve the immunogenicity of recombinant subunits via altering antigen presentation, biodistribution and trafficking.{{cite journal | vauthors = Vartak A, Sucheck SJ | title = Recent Advances in Subunit Vaccine Carriers | journal = Vaccines | volume = 4 | issue = 2 | pages = 12 | date = April 2016 | pmid = 27104575 | doi = 10.3390/vaccines4020012 | pmc = 4931629 | doi-access = free }} Subunits may either be inserted within the carrier or genetically engineered to be expressed on the surface of the vectors for efficient presentation to the mucosal immune system.{{cite journal | vauthors = Liljeqvist S, Ståhl S | title = Production of recombinant subunit vaccines: protein immunogens, live delivery systems and nucleic acid vaccines | journal = Journal of Biotechnology | volume = 73 | issue = 1 | pages = 1–33 | date = July 1999 | pmid = 10483112 | doi = 10.1016/s0168-1656(99)00107-8 }}

• Cannot revert to virulence meaning they cannot cause the disease they aim to protect against{{cite journal | vauthors = Moyle PM, Toth I | title = Modern subunit vaccines: development, components, and research opportunities | journal = ChemMedChem | volume = 8 | issue = 3 | pages = 360–376 | date = March 2013 | pmid = 23316023 | doi = 10.1002/cmdc.201200487 | s2cid = 205647062 }}
• Safe for immunocompromised patients{{cite journal | vauthors = Vartak A, Sucheck SJ | title = Recent Advances in Subunit Vaccine Carriers | journal = Vaccines | volume = 4 | issue = 2 | pages = 12 | date = April 2016 | pmid = 27104575 | pmc = 4931629 | doi = 10.3390/vaccines4020012 | doi-access = free }}
• Can withstand changes in conditions (e.g. temperature, light exposure, humidity)

• Reduced immunogenicity compared to attenuated vaccines
• Require adjuvants 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 immune response
• It is not easy to supervise conjugation chemistry which leads to noncontinuous variation

Recombinant subunit vaccines are safe for administration.{{cite journal | vauthors = Costa AP, Cobucci RN, da Silva JM, da Costa Lima PH, Giraldo PC, Gonçalves AK | title = Safety of Human Papillomavirus 9-Valent Vaccine: A Meta-Analysis of Randomized Trials | journal = Journal of Immunology Research | volume = 2017 | pages = 3736201 | date = 2017 | pmid = 28812030 | pmc = 5546048 | doi = 10.1155/2017/3736201 | doi-access = free }}{{cite journal | vauthors = Cox MM, Izikson R, Post P, Dunkle L | title = Safety, efficacy, and immunogenicity of Flublok in the prevention of seasonal influenza in adults | journal = Therapeutic Advances in Vaccines | volume = 3 | issue = 4 | pages = 97–108 | date = July 2015 | pmid = 26478817 | pmc = 4591523 | doi = 10.1177/2051013615595595 }} However, mild local reactions, including induration and swelling of the injection site, along with fever, fatigue and headache may be encountered after vaccination.{{cite journal | vauthors = James SF, Chahine EB, Sucher AJ, Hanna C | title = Shingrix: The New Adjuvanted Recombinant Herpes Zoster Vaccine | journal = The Annals of Pharmacotherapy | volume = 52 | issue = 7 | pages = 673–680 | date = July 2018 | pmid = 29457489 | doi = 10.1177/1060028018758431 | s2cid = 206644211 }}{{Cite web |date=2022-04-06 |title=Possible Side effects from Vaccines |url=https://www.cdc.gov/vaccines/vac-gen/side-effects.htm |access-date=2022-04-13 |website=U.S. Centers for Disease Control and Prevention (CDC) |archive-date=2017-03-17 |archive-url=https://web.archive.org/web/20170317050028/https://www.cdc.gov/vaccines/vac-gen/side-effects.htm |url-status=live }} Occurrence of severe hypersensitivity reactions and anaphylaxis is rare,{{cite journal | vauthors = McNeil MM, DeStefano F | title = Vaccine-associated hypersensitivity | journal = The Journal of Allergy and Clinical Immunology | volume = 141 | issue = 2 | pages = 463–472 | date = February 2018 | pmid = 29413255 | pmc = 6602527 | doi = 10.1016/j.jaci.2017.12.971 }} but can possibly lead to deaths of individuals. Adverse effects can vary among populations depending on their physical health condition, age, gender and genetic predisposition.{{cite journal | vauthors = Fink AL, Klein SL | title = Sex and Gender Impact Immune Responses to Vaccines Among the Elderly | journal = Physiology | volume = 30 | issue = 6 | pages = 408–416 | date = November 2015 | pmid = 26525340 | pmc = 4630198 | doi = 10.1152/physiol.00035.2015 }}{{cite journal | vauthors = Crowe JE | title = Genetic predisposition for adverse events after vaccination | journal = The Journal of Infectious Diseases | volume = 196 | issue = 2 | pages = 176–177 | date = July 2007 | pmid = 17570102 | doi = 10.1086/518800 | s2cid = 14121320 }}

Recombinant subunit vaccines are contraindicated to people who have experienced allergic reactions and anaphylaxis to antigens or other components of the vaccines previously.{{Cite web |date=2022-03-22 |title=ACIP Contraindications Guidelines for Immunization |url=https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/contraindications.html |access-date=2022-04-14 |website=U.S. Centers for Disease Control and Prevention (CDC) |archive-date=2019-05-01 |archive-url=https://web.archive.org/web/20190501034917/https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/contraindications.html |url-status=live }}{{Cite web |author=Public Health Agency of Canada |date=2007-07-18 |title=Contraindications and precautions: Canadian Immunization Guide |url=https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-2-vaccine-safety/page-3-contraindications-precautions-concerns.html |access-date=2022-04-14 |website=www.canada.ca |archive-date=2023-05-25 |archive-url=https://web.archive.org/web/20230525150921/https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-2-vaccine-safety/page-3-contraindications-precautions-concerns.html |url-status=live }} Furthermore, precautions should be taken when administering vaccines to people who are in diseased state and during pregnancy, in which their injections should be delayed until their conditions become stable and after childbirth respectively.

File:Engerix B (Hepatitis B) vaccine.jpg

ENGERIX-B (produced by GSK) and RECOMBIVAX HB (produced by merck) are two recombinant subunit vaccines licensed for the protection against hepatitis B. Both contain HBsAg harvested and purified from Saccharomyces cerevisiae and are formulated as a suspension of the antigen adjuvanted with alum.{{Cite web |title=RECOMBIVAX HB Hepatitis B Vaccine (Recombinant) |website=Food and Drug Administration |url=https://www.fda.gov/files/vaccines%2C%20blood%20%26%20biologics/published/package-insert-recombivax-hb.pdf |access-date=2023-04-02 |archive-date=2023-05-19 |archive-url=https://web.archive.org/web/20230519052432/https://www.fda.gov/files/vaccines%2C%20blood%20%26%20biologics/published/package-insert-recombivax-hb.pdf |url-status=live }}{{Cite web |title=ENGERIX-B [Hepatitis B Vaccine (Recombinant)] |website=Food and Drug Administration |url=https://www.fda.gov/files/vaccines%2C%20blood%20%26%20biologics/published/Package-Insert---ENGERIX-B.pdf |access-date=2023-04-02 |archive-date=2022-04-08 |archive-url=https://web.archive.org/web/20220408031252/https://www.fda.gov/files/vaccines%2C%20blood%20%26%20biologics/published/Package-Insert---ENGERIX-B.pdf |url-status=live }}

Antibody concentration ≥10mIU/mL against HBsAg are recognized as conferring protection against hepatitis B infection.

It has been shown that primary 3-dose vaccination of healthy individuals is associated with ≥90% seroprotection rates for ENGERIX-B, despite decreasing with older age. Lower seroprotection rates are also associated with presence of underlying chronic diseases and immunodeficiency. Yet, GSK HepB still has a clinically acceptable safety profile in all studied populations.{{cite journal | vauthors = Van Den Ende C, Marano C, Van Ahee A, Bunge EM, De Moerlooze L | title = The immunogenicity and safety of GSK's recombinant hepatitis B vaccine in adults: a systematic review of 30 years of experience | journal = Expert Review of Vaccines | volume = 16 | issue = 8 | pages = 811–832 | date = August 2017 | pmid = 28573913 | doi = 10.1080/14760584.2017.1338568 | s2cid = 4721288 | doi-access = free }}

File:Gardasil vaccine and box.jpg

Cervarix, GARDASIL and GARDASIL9 are three recombinant subunit vaccines licensed for the protection against HPV infection. They differ in the strains which they protect the patients from as Cervarix confers protection against type 16 and 18,{{Cite web |title=CERVARIX [Human Papillomavirus Bivalent (Types 16 and 18) Vaccine, Recombinant] |website=Food and Drug Administration |url=https://www.fda.gov/media/78013/download |access-date=2023-04-02 |archive-date=2023-08-29 |archive-url=https://web.archive.org/web/20230829053628/https://www.fda.gov/media/78013/download |url-status=live }} Gardasil confers protection against type 6, 11, 16 and 18,{{Cite web |title=Gardasil[Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant] |website=Food and Drug Administration |url=https://www.fda.gov/files/vaccines%2C%20blood%20%26%20biologics/published/Package-Insert---Gardasil.pdf |access-date= |archive-date=2023-06-16 |archive-url=https://web.archive.org/web/20230616232624/https://www.fda.gov/files/vaccines,%20blood%20%26%20biologics/published/Package-Insert---Gardasil.pdf |url-status=live }} and Gardasil 9 confers protection against type 6, 11, 16, 18, 31, 33, 45, 52, 58{{Cite web |title=Gardasil 9 (Human Papillomavirus 9-valent Vaccine, Recombinant) |website=Food and Drug Administration |url=https://www.fda.gov/media/90064/download |access-date=2023-04-02 |archive-date=2023-08-29 |archive-url=https://web.archive.org/web/20230829050731/https://www.fda.gov/media/90064/download |url-status=live }} respectively.  The vaccines contain purified VLP of the major capsid L1 protein produced by recombinant Saccharomyces cerevisiae.{{citation needed|date=May 2024}}

It has been shown in a 2014 systematic quantitative review that the bivalent HPV vaccine (Cervarix) is associated with pain (OR 3.29; 95% CI: 3.00–3.60), swelling (OR 3.14; 95% CI: 2.79–3.53) and redness (OR 2.41; 95% CI: 2.17–2.68) being the most frequently reported adverse effects. For Gardasil, the most frequently reported events were pain (OR 2.88; 95% CI: 2.42–3.43) and swelling (OR 2.65; 95% CI: 2.0–3.44).{{cite journal | vauthors = Gonçalves AK, Cobucci RN, Rodrigues HM, de Melo AG, Giraldo PC | title = Safety, tolerability and side effects of human papillomavirus vaccines: a systematic quantitative review | journal = The Brazilian Journal of Infectious Diseases | volume = 18 | issue = 6 | pages = 651–659 | date = 2014 | pmid = 24780368 | doi = 10.1016/j.bjid.2014.02.005 | pmc = 9425215 }}

Gardasil was discontinued in the U.S. on May 8, 2017, after the introduction of Gardasil 9{{Cite web |title=Gardasil-4 is no longer available. |date=23 May 2022 |url=https://www.cdc.gov/vaccines/hcp/vis/what-is-new.html |publisher=U.S. Centers for Disease Control and Prevention (CDC) |access-date=2 April 2023 |archive-date=15 October 2019 |archive-url=https://web.archive.org/web/20191015064022/https://www.cdc.gov/vaccines/hcp/vis/what-is-new.html |url-status=live }} and Cervarix was also voluntarily withdrawn in the U.S. on August 8, 2016.{{Cite web |vauthors=Sagonowsky E |date=2016-10-21 |title=GSK exits U.S. market with its HPV vaccine Cervarix |url=https://www.fiercepharma.com/pharma/gsk-exits-u-s-market-its-hpv-vaccine-cervarix |access-date=2022-03-15 |website=Fierce Pharma |archive-date=2021-07-09 |archive-url=https://web.archive.org/web/20210709184357/https://www.fiercepharma.com/pharma/gsk-exits-u-s-market-its-hpv-vaccine-cervarix |url-status=live }}

Flublok Quadrivalent is a licensed recombinant subunit vaccine for active immunisation against influenza. It contains HA proteins of four strains of influenza virus purified and extracted using the Baculovirus-insect expression system. The four viral strains are standardised annually according to United States Public Health Services (USPHS) requirements.

Flublok Quadrivalent has a comparable safety profile to traditional trivalent and quadrivalent vaccine equivalents. Flublok is also associated with less local reactions (RR = 0.94, 95% CI 0.90–0.98, three RCTs, FEM, I2 = 0%, low‐ certainty evidence) and higher risk of chills (RR = 1.33, 95% CI 1.03–1.72, three RCTs, FEM, I2 = 14%, low‐certainty evidence).{{cite journal | vauthors = O Murchu E, Comber L, Jordan K, Hawkshaw S, Marshall L, O'Neill M, Ryan M, Teljeur C, Carnahan A, Pérez JJ, Robertson AH, Johansen K, Jonge J, Krause T, Nicolay N, Nohynek H, Pavlopoulou I, Pebody R, Penttinen P, Soler-Soneira M, Wichmann O, Harrington P | display-authors = 6 | title = Systematic review of the efficacy, effectiveness and safety of recombinant haemagglutinin seasonal influenza vaccines for the prevention of laboratory-confirmed influenza in individuals ≥18 years of age | journal = Reviews in Medical Virology | pages = e2331 | date = February 2022 | volume = 33 | issue = 3 | pmid = 35106885 | doi = 10.1002/rmv.2331 | s2cid = 246475234 }}

SHINGRIX is a licensed recombinant subunit vaccine for protection against Herpes Zoster, whose risk of developing increases with decline of varicella zoster virus (VZV) specific immunity. The vaccine contains VZV gE antigen component extracted from CHO cells, which is to be reconstituted with adjuvant suspension AS01_B.

Systematic reviews and meta-analyses have been conducted on the efficacy, effectiveness and safety of SHINGRIX in immunocompromised 18–49 year old patients and healthy adults aged 50 and over. These studies reported humoral and cell-mediated immunity rate ranged between 65.4 and 96.2% and 50.0–93.0% while efficacy in patients (18–49 yo) with haematological malignancies was estimated at 87.2% (95%CI, 44.3–98.6%) up to 13 months post-vaccination with an acceptable safety profile.{{cite journal | vauthors = Racine É, Gilca V, Amini R, Tunis M, Ismail S, Sauvageau C | title = A systematic literature review of the recombinant subunit herpes zoster vaccine use in immunocompromised 18-49 year old patients | journal = Vaccine | volume = 38 | issue = 40 | pages = 6205–6214 | date = September 2020 | pmid = 32788132 | doi = 10.1016/j.vaccine.2020.07.049 | s2cid = 221123883 }}{{cite journal | vauthors = Tricco AC, Zarin W, Cardoso R, Veroniki AA, Khan PA, Nincic V, Ghassemi M, Warren R, Sharpe JP, Page AV, Straus SE | display-authors = 6 | title = Efficacy, effectiveness, and safety of herpes zoster vaccines in adults aged 50 and older: systematic review and network meta-analysis | journal = BMJ | volume = 363 | pages = k4029 | date = October 2018 | pmid = 30361202 | pmc = 6201212 | doi = 10.1136/bmj.k4029 }}

NUVAXOVID is a recombinant subunit vaccine licensed for the prevention of SARS-CoV-2 infection. Market authorization was issued on 20 December 2021.{{Cite web |title=Nuvaxovid COVID-19 Vaccine (recombinant, adjuvanted) |date=17 December 2021 |url=https://www.ema.europa.eu/en/medicines/human/EPAR/nuvaxovid#authorisation-details-section |access-date=2 April 2023 |archive-date=23 December 2021 |archive-url=https://web.archive.org/web/20211223093752/https://www.ema.europa.eu/en/medicines/human/EPAR/nuvaxovid#authorisation-details-section |url-status=live }} The vaccine contains the SARS-CoV-2 spike protein produced using the baculovirus expression system, which is eventually adjuvanted with the Matrix M adjuvant.

While the practice of immunisation can be traced back to the 12th century, in which ancient Chinese at that time employed the technique of variolation to confer immunity to smallpox infection,{{Citation needed|date=May 2022}} the modern era of vaccination has a short history of around 200 years. It began with the invention of a vaccine by Edward Jenner in 1798 to eradicate smallpox by injecting relatively weaker cowpox virus into the human body.{{citation needed|date=May 2024}}

The middle of the 20th century marked the golden age of vaccine science.{{citation needed|date=May 2022}} Rapid technological advancements during this period of time enabled scientists to cultivate cell culture under controlled environments in laboratories,{{cite journal | vauthors = Plotkin S | title = History of vaccination | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 111 | issue = 34 | pages = 12283–12287 | date = August 2014 | pmid = 25136134 | pmc = 4151719 | doi = 10.1073/pnas.1400472111 | bibcode = 2014PNAS..11112283P | doi-access = free }} subsequently giving rise to the production of vaccines against poliomyelitis, measles and various communicable diseases.{{citation needed|date=May 2022}} Conjugated vaccines were also developed using immunologic markers including capsular polysaccharide and proteins. Creation of products targeting common illnesses successfully lowered infection-related mortality and reduced public healthcare burden.

Emergence of genetic engineering techniques revolutionised the creation of vaccines. By the end of the 20th century, researchers had the ability to create recombinant vaccines apart from traditional whole-cell vaccine, for instance Hepatitis B vaccine, which uses the viral antigens to initiate immune responses.

As the manufacturing methods continue to evolve, vaccines with more complex constitutions will inevitably be generated in the future to extend their therapeutic applications to both infectious and non-infectious diseases,{{citation needed|date=May 2022}} in order to safeguard the health of more people.

Recombinant subunit vaccines are used in development for tuberculosis,{{cite journal | vauthors = Mascola JR, Fauci AS | title = Novel vaccine technologies for the 21st century | journal = Nature Reviews. Immunology | volume = 20 | issue = 2 | pages = 87–88 | date = February 2020 | pmid = 31712767 | pmc = 7222935 | doi = 10.1038/s41577-019-0243-3 }} dengue fever, soil-transmitted helminths,{{cite journal | vauthors = Noon JB, Aroian RV | title = Recombinant subunit vaccines for soil-transmitted helminths | journal = Parasitology | volume = 144 | issue = 14 | pages = 1845–1870 | date = December 2017 | pmid = 28770689 | pmc = 5729844 | doi = 10.1017/S003118201700138X }} feline leukaemia{{cite journal | vauthors = Marciani DJ, Kensil CR, Beltz GA, Hung CH, Cronier J, Aubert A | title = Genetically-engineered subunit vaccine against feline leukaemia virus: protective immune response in cats | journal = Vaccine | volume = 9 | issue = 2 | pages = 89–96 | date = February 1991 | pmid = 1647576 | doi = 10.1016/0264-410x(91)90262-5 }} and COVID-19.{{cite journal | vauthors = Chen WH, Hotez PJ, Bottazzi ME | title = Potential for developing a SARS-CoV receptor-binding domain (RBD) recombinant protein as a heterologous human vaccine against coronavirus infectious disease (COVID)-19 | journal = Human Vaccines & Immunotherapeutics | volume = 16 | issue = 6 | pages = 1239–1242 | date = June 2020 | pmid = 32298218 | doi = 10.1080/21645515.2020.1740560 | pmc = 7482854 }}

Subunit vaccines are not only considered effective for SARS-COV-2, but also as candidates for evolving immunizations against malaria, tetanus, salmonella enterica, and other diseases.

Research has been conducted to explore the possibility of developing a heterologous SARS-CoV receptor-binding domain (RBD) recombinant protein as a human vaccine against COVID-19. The theory is supported by evidence that convalescent serum from SARS-CoV patients have the ability to neutralise SARS-CoV-2 (corresponding virus for COVID-19) and that amino acid similarity between SARS-CoV and SARS-CoV-2 spike and RBD protein is high (82%).

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Category:Vaccines

Category:Pharmacology