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Subunit vaccine
open-in-new
<h2 id="discovery">Discovery</h2> <p>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.<a class="footnote-ref" id="fnref:16" href="#fn:16"><sup>16</sup></a> </p> <h2 id="mechanism">Mechanism</h2> <p>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 <a href="/facts/Side_effect/PhuX2haY">side effects</a> is minimal.<a class="footnote-ref" id="fnref:17" href="#fn:17"><sup>17</sup></a> An effective vaccine would elicit the immune response to the antigens and form <a href="/facts/Immunological_memory/PVTllYEY">immunological memory</a> that allows quick recognition of the pathogens and quick response to future infections.<a class="footnote-ref" id="fnref:18" href="#fn:18"><sup>18</sup></a> </p><p>A drawback is that the specific antigens used in a subunit vaccine may lack <a href="/facts/Pathogen-associated_molecular_pattern/jLrjQv7T">pathogen-associated molecular patterns</a> which are common to a class of pathogen. These <a href="/facts/Molecular_structure/N9ljSfFq">molecular structures</a> may be used by <a href="/facts/Immune_cell/vsDunUK0">immune cells</a> for danger recognition, so without them, the immune response may be weaker. Another drawback is that the antigens do not infect <a href="/facts/Cell_(biology)/bLM9UQvy">cells</a>, so the immune response to the subunit vaccines may only be <a href="/facts/Humoral_immunity/qG9I4pGf">antibody-mediated</a>, not <a href="/facts/Cell-mediated/vPX39rt1">cell-mediated</a>, and as a result, is weaker than those elicited by other types of vaccines. To increase immune response, <a href="/facts/Immunologic_adjuvant/nMbqU16c">adjuvants</a> may be used with the subunit vaccines, or booster doses may be required.<a class="footnote-ref" id="fnref:19" href="#fn:19"><sup>19</sup></a> </p> <h2 id="types">Types</h2> Summary of subunit vaccine types<a class="footnote-ref" id="fnref:20" href="#fn:20"><sup>20</sup></a><a class="footnote-ref" id="fnref:21" href="#fn:21"><sup>21</sup></a><table><tbody><tr><th>Types</th><th>Description</th><th>Examples</th></tr><tr><td>Protein subunit</td><td>contains <a href="/facts/Protein_subunit/HhuET9UP">isolated proteins</a> from <a href="/facts/Pathogen/axMXtV1M">pathogens</a> (<a href="/facts/Virus/mf88Bcbl">virus</a> or <a href="/facts/Bacteria/wC8xSCsU">bacteria</a>)</td><td><a href="/facts/Hepatitis_B_vaccine/j2gQw4Sc">hepatitis B</a>, <a href="/facts/Acellular_pertussis_vaccine/aobtroMC">acellular pertussis vaccines</a></td></tr><tr><td>Polysaccharide</td><td>contains chains of <a href="/facts/Polysaccharide/lqXq2cJU">polysaccharides</a> (sugar molecules) found in the pathogen's capsule such as <a href="/facts/Bacterial_wall/0UHPLKKF">cell walls of some bacteria</a></td><td><a href="/facts/Pneumococcal_polysaccharide_vaccine/79JHhKBy">pneumococcal polysaccharide vaccine</a>, <a href="/facts/Meningococcal_vaccine/FmWdsBCV">meningococcal vaccine</a> preventing diseases from <i><a href="/facts/Neisseria_meningitidis/u4SqwHuc">Neisseria meningitidis</a></i> <a href="/facts/Serotype/fUllA0xY">group</a> A, C, W-135, and Y</td></tr><tr><td>Conjugate</td><td>contains polysaccharide chains bound to <a href="/facts/Membrane_transport_protein/h1aczVxg">carrier proteins</a>, such as <a href="/facts/Diphtheria_toxoid/XCurRd9m">diphtheria</a> and <a href="/facts/Tetanus_toxoid/Ee1Bw1a9">tetanus toxoid</a>, to boost the <a href="/facts/Immune_response/dtLulqIy">immune response</a></td><td><a href="/facts/Pneumococcal_conjugate_vaccine/IxaeBXot">pneumococcal conjugate vaccine</a>, <a href="/facts/Hib_vaccine/bU0eKdDv">haemophilus influenzae type b conjugate vaccine</a>, <a href="/facts/Meningococcal_vaccine/FmWdsBCV">meningococcal conjugate vaccine</a></td></tr></tbody></table> <h3>Protein subunit</h3> <p>A <a href="/facts/Protein_subunit/HhuET9UP">protein subunit</a> is a <a href="/facts/Polypeptide_chain/C4ltc7UG">polypeptide chain</a> or <a href="/facts/Protein/Jxmagu3E">protein</a> molecule that assembles (or "<i>coassembles</i>") with other protein molecules to form a <a href="/facts/Protein_complex/GW11Ee34">protein complex</a>.<a class="footnote-ref" id="fnref:22" href="#fn:22"><sup>22</sup></a><a class="footnote-ref" id="fnref:23" href="#fn:23"><sup>23</sup></a><a class="footnote-ref" id="fnref:24" href="#fn:24"><sup>24</sup></a> Large assemblies of proteins such as <a href="/facts/Viruses/mf88Bcbl">viruses</a> often use a small number of types of protein subunits as building blocks.<a class="footnote-ref" id="fnref:25" href="#fn:25"><sup>25</sup></a> 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 <a href="/facts/Capsid/hm7V6Ewm">capsid</a> 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.<a class="footnote-ref" id="fnref:26" href="#fn:26"><sup>26</sup></a> Another protein-based approach involves self‐assembly of multiple protein subunits into a <a href="/facts/Virus-like_particle/32B60efL">virus-like particle</a> (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.<a class="footnote-ref" id="fnref:27" href="#fn:27"><sup>27</sup></a><a class="footnote-ref" id="fnref:28" href="#fn:28"><sup>28</sup></a><a class="footnote-ref" id="fnref:29" href="#fn:29"><sup>29</sup></a> </p><p>Protein subunit vaccines are generally made through <a href="/facts/Protein_production/6cWhWJWc">protein production</a>, manipulating the <a href="/facts/Gene_expression/alCPohLR">gene expression</a> of an organism so that it <a href="/facts/Heterologous_expression/AUTNhevE">expresses</a> large amounts of a <a href="/facts/Recombinant_gene/dT3PL7M6">recombinant gene</a>.<a class="footnote-ref" id="fnref:30" href="#fn:30"><sup>30</sup></a><a class="footnote-ref" id="fnref:31" href="#fn:31"><sup>31</sup></a> A variety of approaches can be used for development depending on the vaccine involved.<a class="footnote-ref" id="fnref:32" href="#fn:32"><sup>32</sup></a> <a href="/facts/Yeast/eGD24nfI">Yeast</a>, <a href="/facts/Baculovirus/nT603scg">baculovirus</a>, or <a href="/facts/Chinese_hamster_ovary_cell/t09KCNNc">mammalian</a> cell cultures can be used to produce large amounts of proteins in vitro.<a class="footnote-ref" id="fnref:33" href="#fn:33"><sup>33</sup></a><a class="footnote-ref" id="fnref:34" href="#fn:34"><sup>34</sup></a><a class="footnote-ref" id="fnref:35" href="#fn:35"><sup>35</sup></a> </p><p>Protein-based vaccines are being used for <a href="/facts/Hepatitis_B/qqPTEY3p">hepatitis B</a> and for <a href="/facts/Human_papillomavirus/7XW8mjG2">human papillomavirus</a> (HPV).<a class="footnote-ref" id="fnref:36" href="#fn:36"><sup>36</sup></a><a class="footnote-ref" id="fnref:37" href="#fn:37"><sup>37</sup></a> The approach is being used to try to develop vaccines for difficult-to-vaccinate-against viruses such as <a href="/facts/Ebolavirus/VaToHQAD">ebolavirus</a> and <a href="/facts/HIV/ulY2rgzu">HIV</a>.<a class="footnote-ref" id="fnref:38" href="#fn:38"><sup>38</sup></a> Protein-based vaccines for COVID-19 tend to target either its spike protein or its receptor binding domain.<a class="footnote-ref" id="fnref:39" href="#fn:39"><sup>39</sup></a> As of 2021, the most researched vaccine platform for COVID-19 worldwide was reported to be recombinant protein subunit vaccines.<a class="footnote-ref" id="fnref:40" href="#fn:40"><sup>40</sup></a><a class="footnote-ref" id="fnref:41" href="#fn:41"><sup>41</sup></a> </p> <h3>Polysaccharide subunit</h3> <p><a href="/facts/Vi_capsular_polysaccharide_vaccine/GFCe3l3R">Vi capsular polysaccharide vaccine</a> (ViCPS) against <a href="/facts/Typhoid/bKPTIYLl">typhoid</a> caused by the Typhi serotype of <i>Salmonella enterica</i>.<a class="footnote-ref" id="fnref:42" href="#fn:42"><sup>42</sup></a> Instead of being a protein, the Vi antigen is a <a href="/facts/Bacterial_capsule/FVSHDlXL">bacterial capsule</a> polysacchide, made up of a long sugar chain linked to a lipid.<a class="footnote-ref" id="fnref:43" href="#fn:43"><sup>43</sup></a> Capsular vaccines like ViCPS tend to be weak at eliciting immune responses in children. Making a <a href="/facts/Conjugate_vaccine/DwqFnI4L">conjugate vaccine</a> by linking the polysacchide with a <a href="/facts/Toxoid/qFAvxp7C">toxoid</a> increases the efficacy.<a class="footnote-ref" id="fnref:44" href="#fn:44"><sup>44</sup></a> </p> <h3>Conjugate vaccine</h3> <p class="note">Main article: <a href="/facts/Conjugate_vaccine/DwqFnI4L">Conjugate vaccine</a></p> <p>A <a href="/facts/Conjugate_vaccine/DwqFnI4L">conjugate vaccine</a> is a type of <a href="/facts/Vaccine/QcXzLug2">vaccine</a> which combines a weak <a href="/facts/Antigen/9JlAernG">antigen</a> with a strong antigen as a carrier so that the <a href="/facts/Immune_system/HRCTf1pb">immune system</a> has a stronger response to the weak antigen.<a class="footnote-ref" id="fnref:45" href="#fn:45"><sup>45</sup></a> </p> <h3>Peptide subunit</h3> <p>A <a href="/facts/Peptide_vaccine/6Bzph9Hs">peptide-based subunit vaccine</a> employs a <a href="/facts/Peptide/C4ltc7UG">peptide</a> instead of a full <a href="/facts/Protein/Jxmagu3E">protein</a>.<a class="footnote-ref" id="fnref:46" href="#fn:46"><sup>46</sup></a> 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.<a class="footnote-ref" id="fnref:47" href="#fn:47"><sup>47</sup></a> Three steps occur leading to creation of peptide subunit vaccine;<a class="footnote-ref" id="fnref:48" href="#fn:48"><sup>48</sup></a> </p> <ol><li>Epitope recognition</li> <li>Epitope optimization</li> <li>Peptide immunity improvement</li></ol> <h2 id="features">Features</h2> <p>When compared with conventional <a href="/facts/Attenuated_vaccine/Gabb4afu">attenuated vaccines</a> and <a href="/facts/Inactivated_vaccine/R1onnWMB">inactivated vaccines</a>, recombinant subunit vaccines have the following special characteristics: </p> <ul><li>They contain clearly identified compositions which greatly reduces the possibility of presence of undesired materials within the <a href="/facts/Vaccine/QcXzLug2">vaccine</a>.</li> <li>Their pathogenicities are minimized as only fragments of the pathogen are present in the <a href="/facts/Vaccine/QcXzLug2">vaccine</a> which cannot invade and multiply within the human body.<a class="footnote-ref" id="fnref:49" href="#fn:49"><sup>49</sup></a></li> <li>They have better <a href="/facts/Safety_profile/4v2PDxCM">safety profiles</a><a class="footnote-ref" id="fnref:50" href="#fn:50"><sup>50</sup></a> and are suitable to be administered to <a href="/facts/Immunodeficiency/CIEujXmc">immunocompromised</a> patients.<a class="footnote-ref" id="fnref:51" href="#fn:51"><sup>51</sup></a></li> <li>They are suitable for <a href="/facts/Mass_production/31Cmgjuc">mass production</a> due to the use of recombinant technologies.</li> <li>They have high stability so they can withstand environmental changes and are more convenient to be used in community settings.<a class="footnote-ref" id="fnref:52" href="#fn:52"><sup>52</sup></a></li></ul> <p>However, there are also some drawbacks regarding recombinant subunit vaccines: </p> <ul><li>Addition of <a href="/facts/Immunologic_adjuvant/nMbqU16c">adjuvants</a> is necessary during <a href="/facts/Manufacturing/3qW7bcdy">manufacturing</a> to increase the <a href="/facts/Efficacy/PNlTeDtD">efficacy</a> of these vaccines.<a class="footnote-ref" id="fnref:53" href="#fn:53"><sup>53</sup></a></li> <li>Patients will have to receive <a href="/facts/Booster_dose/A1tv9SVq">booster doses</a> to maintain long-term <a href="/facts/Immunity_(medical)/vLPpzSNL">immunity</a>.<a class="footnote-ref" id="fnref:54" href="#fn:54"><sup>54</sup></a><a class="footnote-ref" id="fnref:55" href="#fn:55"><sup>55</sup></a></li> <li>Selection of appropriate cell lines for the cultivation of subunits is time-consuming because microbial proteins can be incompatible to certain <a href="/facts/Expression_systems/alCPohLR">expression systems</a>.<a class="footnote-ref" id="fnref:56" href="#fn:56"><sup>56</sup></a></li></ul> <h2 id="pharmacology">Pharmacology</h2> <p><a href="/facts/Vaccination/3SfpzPsd">Vaccination</a> is a potent way to protect individuals against <a href="/facts/Infectious_diseases/182XrncP">infectious diseases</a>.<a class="footnote-ref" id="fnref:57" href="#fn:57"><sup>57</sup></a> </p><p><a href="/facts/Active_immunity/bc7zT1Jo">Active immunity</a> can be acquired artificially by <a href="/facts/Vaccination/3SfpzPsd">vaccination</a> as a result of the body's own defense mechanism being triggered by the exposure of a small, controlled amount of <a href="/facts/Pathogen/axMXtV1M">pathogenic</a> substances to produce its own antibodies and memory cells without being infected by the real pathogen.<a class="footnote-ref" id="fnref:58" href="#fn:58"><sup>58</sup></a> </p><p>The processes involved in primary immune response are as follows: </p> <ol><li>Pre-exposure to the <a href="/facts/Antigen/9JlAernG">antigens</a> present in <a href="/facts/Vaccine/QcXzLug2">vaccines</a> elicits a primary response. After injection, antigens will be <a href="/facts/Phagocytosis/eBrv2XKV">ingested</a> by <a href="/facts/Antigen-presenting_cells/No0wr2uU">antigen-presenting cells (APCs)</a>, such as <a href="/facts/Dendritic_cell/19KBuKFK">dendritic cells</a> and <a href="/facts/Macrophage/z7hkQu3o">macrophages</a>, via <a href="/facts/Phagocytosis/eBrv2XKV">phagocytosis</a>.<a class="footnote-ref" id="fnref:59" href="#fn:59"><sup>59</sup></a><a class="footnote-ref" id="fnref:60" href="#fn:60"><sup>60</sup></a></li> <li>The <a href="/facts/Antigen-presenting_cell/No0wr2uU">APCs</a> will travel to <a href="/facts/Lymph_node/vkwfcQjH">lymph nodes</a>, where immature <a href="/facts/B_cell/6Y1tgwwp">B cells</a> and <a href="/facts/T_cell/5z6PQ9UN">T cells</a> are present.<a class="footnote-ref" id="fnref:61" href="#fn:61"><sup>61</sup></a></li> <li>Following antigen processes by <a href="/facts/Antigen-presenting_cell/No0wr2uU">APCs</a>, antigens will bind to either <a href="/facts/MHC_class_I/5VsuyBc4">MHC class I receptors</a> or <a href="/facts/MHC_class_II/nQ4hkBgW">MHC class II receptors</a> on the cell surface of the cells based on their compositional and structural features to form complexes.<a class="footnote-ref" id="fnref:62" href="#fn:62"><sup>62</sup></a></li> <li><a href="/facts/Antigen_presentation/RMEAcYwR">Antigen presentation</a> occurs, in which <a href="/facts/T-cell_receptor/zDqyWyG4">T cell receptors</a> attach to the antigen-MHC complexes, initiating <a href="/facts/Clonal_hematopoiesis/AXVuoHml">clonal expansion</a> and <a href="/facts/Cellular_differentiation/bCVqUG7w">differentiation</a>, and hence the conversion of <a href="/facts/Naive_T_cell/QEl3A7Yh">naive T cells</a> to <a href="/facts/CD8%2B/e5eRg3XJ">cytotoxic T cells (CD8+)</a> or <a href="/facts/T_helper_cell/nhwAYkDj">helper T cells (CD4+)</a>.<a class="footnote-ref" id="fnref:63" href="#fn:63"><sup>63</sup></a><a class="footnote-ref" id="fnref:64" href="#fn:64"><sup>64</sup></a></li> <li><a href="/facts/Cytotoxic_T_cell/e5eRg3XJ">Cytotoxic CD8+ cells</a> can directly destroy the <a href="/facts/Infection/182XrncP">infected</a> cells containing the <a href="/facts/Antigen/9JlAernG">antigens</a> that were presented to them by the <a href="/facts/Antigen-presenting_cell/No0wr2uU">APCs</a> by releasing lytic molecules, while <a href="/facts/T_helper_cell/nhwAYkDj">helper CD4+ cells</a> are responsible for the secretion of <a href="/facts/Cytokine/SdWpWABH">cytokines</a> that activates <a href="/facts/B_cell/6Y1tgwwp">B cells</a> and <a href="/facts/Cytotoxic_T_cell/e5eRg3XJ">cytotoxic T cells</a>.<a class="footnote-ref" id="fnref:65" href="#fn:65"><sup>65</sup></a><a class="footnote-ref" id="fnref:66" href="#fn:66"><sup>66</sup></a></li> <li><a href="/facts/B_cell/6Y1tgwwp">B cells</a> can undergo activation in the absence of <a href="/facts/T_cell/5z6PQ9UN">T cells</a> via the <a href="/facts/B_cell/6Y1tgwwp">B cell</a> receptor signalling pathway.<a class="footnote-ref" id="fnref:67" href="#fn:67"><sup>67</sup></a></li> <li>After <a href="/facts/Dendritic_cell/19KBuKFK">dendritic cells</a> capture the <a href="/facts/Immunogen/r03RnQmH">immunogen</a> present in the <a href="/facts/Vaccine/QcXzLug2">vaccine</a>, they can present the substances to <a href="/facts/Naive_B_cell/x8DHko12">naive B cells</a>, causing the <a href="/facts/Cell_proliferation/Jp3hWo2t">proliferation</a> of <a href="/facts/Plasma_cell/1fY4bFHR">plasma cells</a> for <a href="/facts/Antibody/MX8pdTdP">antibody</a> production.<a class="footnote-ref" id="fnref:68" href="#fn:68"><sup>68</sup></a> <a href="/facts/Isotype_switching/q8w8PWoY">Isotype switching</a> can take place during <a href="/facts/B_cell/6Y1tgwwp">B cell</a> development for the formation of different antibodies, including <a href="/facts/Immunoglobulin_G/cKzc83tk">IgG</a>, <a href="/facts/Immunoglobulin_E/76uGAl7k">IgE</a> and <a href="/facts/Immunoglobulin_A/G0HzhnWt">IgA</a>.<a class="footnote-ref" id="fnref:69" href="#fn:69"><sup>69</sup></a></li> <li><a href="/facts/Memory_B_cell/3Qaz8Pxd">Memory B cells</a> and <a href="/facts/Memory_T_cell/xsavrTuS">T cells</a> are formed post-infection.<a class="footnote-ref" id="fnref:70" href="#fn:70"><sup>70</sup></a> The <a href="/facts/Antigen/9JlAernG">antigens</a> are memorised by these cells so that subsequent exposure to the same type of antigens will stimulate a <a href="/facts/Secondary_immune_response/dtLulqIy">secondary response</a>, in which a higher concentration of <a href="/facts/Antibody/MX8pdTdP">antibodies</a> specific for the <a href="/facts/Antigen/9JlAernG">antigens</a> are reproduced rapidly and efficiently in a short time for the elimination of the <a href="/facts/Pathogen/axMXtV1M">pathogen</a>.<a class="footnote-ref" id="fnref:71" href="#fn:71"><sup>71</sup></a></li></ol> <p>Under specific circumstances, low doses of <a href="/facts/Vaccine/QcXzLug2">vaccines</a> are given initially, followed by additional doses named <a href="/facts/Booster_dose/A1tv9SVq">booster doses</a>. Boosters can effectively maintain the level of <a href="/facts/Memory_T_cell/xsavrTuS">memory cells</a> in the human body, hence extending a person's <a href="/facts/Immunity_(medical)/vLPpzSNL">immunity</a>.<a class="footnote-ref" id="fnref:72" href="#fn:72"><sup>72</sup></a><a class="footnote-ref" id="fnref:73" href="#fn:73"><sup>73</sup></a><a class="footnote-ref" id="fnref:74" href="#fn:74"><sup>74</sup></a> </p> <h2 id="manufacturing">Manufacturing</h2> <p>The manufacturing process of recombinant subunit <a href="/facts/Vaccine/QcXzLug2">vaccines</a> are as follows: </p> <ol><li>Identification of <a href="/facts/Immunogenicity/QVxzK4tD">immunogenic</a> subunit</li> <li>Subunit <a href="/facts/Expression_vector/yqjSkTgE">expression</a> and synthesis</li> <li>Extraction and purification</li> <li>Addition of <a href="/facts/Adjuvant/jnRqeBnG">adjuvants</a> or incorporation to <a href="/facts/Vectors_in_gene_therapy/hH43tmyn">vectors</a></li> <li><a href="/facts/Formulation/GyvpXvsL">Formulation</a> and delivery.</li></ol> <h3>Identification of immunogenic subunit</h3> <p>Candidate subunits will be selected primarily by their <a href="/facts/Immunogenicity/QVxzK4tD">immunogenicity</a>.<a class="footnote-ref" id="fnref:75" href="#fn:75"><sup>75</sup></a> To be <a href="/facts/Immunogenicity/QVxzK4tD">immunogenic</a>, they should be of foreign nature and of sufficient complexity for the reaction between different components of the <a href="/facts/Immune_system/HRCTf1pb">immune system</a> and the candidates to occur.<a class="footnote-ref" id="fnref:76" href="#fn:76"><sup>76</sup></a> Candidates are also selected based on size, nature of function (e.g. <a href="/facts/Cell_signaling/6oYAVP9I">signalling</a>) and cellular location (e.g. <a href="/facts/Transmembrane_protein/0vQH5HrM">transmembrane</a>).<a class="footnote-ref" id="fnref:77" href="#fn:77"><sup>77</sup></a> </p> <h3>Subunit expression and synthesis</h3> <p>Upon identifying the target subunit and its encoding <a href="/facts/Gene/e1swwPY6">gene</a>, the <a href="/facts/Gene/e1swwPY6">gene</a> will be isolated and transferred to a second, non-pathogenic organism, and cultured for <a href="/facts/Mass_production/31Cmgjuc">mass production</a>.<a class="footnote-ref" id="fnref:78" href="#fn:78"><sup>78</sup></a> The process is also known as <a href="/facts/Heterologous_expression/AUTNhevE">heterologous expression</a>. </p><p>A suitable <a href="/facts/Expression_vector/yqjSkTgE">expression system</a> is selected based on the requirement of <a href="/facts/Post-translational_modification/KMUayTIc">post-translational modifications</a>, costs, ease of product extraction and production efficiency. Commonly used systems for both licensed and developing recombinant subunit <a href="/facts/Vaccine/QcXzLug2">vaccines</a> include <a href="/facts/Bacteria/wC8xSCsU">bacteria</a>, <a href="/facts/Yeast/eGD24nfI">yeast</a>, <a href="/facts/Mammal/phSwTzBo">mammalian</a> cells, <a href="/facts/Insect/IgDNvnUL">insect</a> cells.<a class="footnote-ref" id="fnref:79" href="#fn:79"><sup>79</sup></a> </p> <h4>Bacterial cells</h4> <p><a href="/facts/Bacteria/wC8xSCsU">Bacterial cells</a> are widely used for <a href="/facts/Cloning_vector/s4peCwGf">cloning processes</a>, <a href="/facts/Genetic_engineering/vwdlDR61">genetic modification</a> and small-scale productions.<a class="footnote-ref" id="fnref:80" href="#fn:80"><sup>80</sup></a> <a href="/facts/Escherichia_coli/nR4Gvl56">Escherichia coli (E. Coli)</a> is widely utilised due to its highly explored <a href="/facts/Genetics/bu8wne0A">genetics</a>, widely available genetic tools for <a href="/facts/Gene_expression/alCPohLR">gene expression</a>, accurate profiling and its ability to grow in inexpensive <a href="/facts/Growth_medium/97IMkpFP">media</a> at high cell densities.<a class="footnote-ref" id="fnref:81" href="#fn:81"><sup>81</sup></a> </p><p>E. Coli is mostly appropriate for structurally simple proteins owing to its inability to carry out <a href="/facts/Post-translational_modifications/KMUayTIc">post-translational modifications</a>, lack of <a href="/facts/Protein_secretion/FI9XYhHE">protein secretary system</a> and the potential for producing <a href="/facts/Inclusion_bodies/TJnRUnT0">inclusion bodies</a> that require additional solubilisation.<a class="footnote-ref" id="fnref:82" href="#fn:82"><sup>82</sup></a><a class="footnote-ref" id="fnref:83" href="#fn:83"><sup>83</sup></a><a class="footnote-ref" id="fnref:84" href="#fn:84"><sup>84</sup></a> Regarding application, <a href="/facts/Escherichia_coli/nR4Gvl56">E.Coli</a> is being utilised as the <a href="/facts/Expression_vector/yqjSkTgE">expression system</a> of the <a href="/facts/Dengue_vaccine/j4ktXsAU">dengue vaccine</a>.<a class="footnote-ref" id="fnref:85" href="#fn:85"><sup>85</sup></a> </p> <h4>Yeast</h4> <p><a href="/facts/Yeast/eGD24nfI">Yeast</a> matches <a href="/facts/Bacteria/wC8xSCsU">bacterial cells'</a> cost-effectiveness, efficiency and technical feasibility.<a class="footnote-ref" id="fnref:86" href="#fn:86"><sup>86</sup></a> Moreover, <a href="/facts/Yeast/eGD24nfI">yeast</a> secretes <a href="/facts/Soluble/kLE9h3Jb">soluble</a> <a href="/facts/Protein/Jxmagu3E">proteins</a> and has the ability to perform <a href="/facts/Post-translational_modification/KMUayTIc">post-translational modifications</a> similar to <a href="/facts/Mammal/phSwTzBo">mammalian</a> cells.<a class="footnote-ref" id="fnref:87" href="#fn:87"><sup>87</sup></a> </p> <p>Notably, yeast incorporates more <a href="/facts/Mannose/U05bJ7p8">mannose</a> molecules during <a href="/facts/N-linked_glycosylation/7W9cDU3q">N-glycosylation</a> when compared with other <a href="/facts/Eukaryote/SkwyPLMA">eukaryotes</a>,<a class="footnote-ref" id="fnref:88" href="#fn:88"><sup>88</sup></a> which may trigger <a href="/facts/Cellular_stress_response/cJodtRUo">cellular conformational stress responses</a>. Such responses may result in failure in reaching native protein conformation, implying potential reduction of <a href="/facts/Half-life/kGVH8BAB">serum half-life</a> and <a href="/facts/Immunogenicity/QVxzK4tD">immunogenicity</a>.<a class="footnote-ref" id="fnref:89" href="#fn:89"><sup>89</sup></a> Regarding application, both the <a href="/facts/HBsAg/PBxJ0fve">hepatitis B virus surface antigen</a> (<a href="/facts/HBsAg/PBxJ0fve">HBsAg</a>) and the <a href="/facts/Virus-like_particle/32B60efL">virus-like particles</a> (<a href="/facts/VLPs/32B60efL">VLPs</a>) of the major capsid protein L1 of <a href="/facts/Human_papillomavirus_infection/7XW8mjG2">human papillomavirus</a> type 6, 11, 16, 18 are produced by <i><a href="/facts/Saccharomyces_cerevisiae/sX9MGFrz">Saccharomyces cerevisiae</a></i>. </p> <h4>Mammalian cells</h4> <p><a href="/facts/Mammal/phSwTzBo">Mammalian</a> cells are well known for their ability to perform therapeutically essential <a href="/facts/Post-translational_modification/KMUayTIc">post-translational modifications</a> and express properly folded, <a href="/facts/Glycosylated/VYEeQCRz">glycosylated</a> and functionally active proteins.<a class="footnote-ref" id="fnref:90" href="#fn:90"><sup>90</sup></a><a class="footnote-ref" id="fnref:91" href="#fn:91"><sup>91</sup></a><a class="footnote-ref" id="fnref:92" href="#fn:92"><sup>92</sup></a> However, efficacy of mammalian cells may be limited by <a href="/facts/Epigenetics/UfAAERcn">epigenetic</a> <a href="/facts/Gene_silencing/mh0JYYPD">gene silencing</a> and <a href="/facts/Aggresome/z3BEc9lU">aggresome</a> formation (recombinant protein aggregation).<a class="footnote-ref" id="fnref:93" href="#fn:93"><sup>93</sup></a> For mammalian cells, synthesised proteins were reported to be secreted into chemically defined media, potentially simplifying protein extraction and purification.<a class="footnote-ref" id="fnref:94" href="#fn:94"><sup>94</sup></a> </p><p>The most prominent example under this class is <a href="/facts/Chinese_hamster_ovary_cell/t09KCNNc">Chinese Hamster Ovary (CHO)</a> cells utilised for the synthesis of recombinant <a href="/facts/Varicella_zoster_virus/ebbSkn9U">varicella zoster virus</a> surface glycoprotein (gE) antigen for <a href="/facts/Shingrix/EgFY6JmK">SHINGRIX</a>.<a class="footnote-ref" id="fnref:95" href="#fn:95"><sup>95</sup></a> <a href="/facts/Chinese_hamster_ovary_cell/t09KCNNc">CHO cells</a> 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 <a href="/facts/Prion/UJfG9EfS">prion</a>-induced contamination.<a class="footnote-ref" id="fnref:96" href="#fn:96"><sup>96</sup></a><a class="footnote-ref" id="fnref:97" href="#fn:97"><sup>97</sup></a> </p> <h4>Baculovirus (insect) cells</h4> <p>The <a href="/facts/Baculoviridae/nT603scg">baculovirus</a>-<a href="/facts/Insect/IgDNvnUL">insect</a> cell <a href="/facts/Expression_vector/yqjSkTgE">expression system</a> has the ability to express a variety of <a href="/facts/Recombinant_proteins/dT3PL7M6">recombinant proteins</a> at high levels and provide significant eukaryotic protein processing capabilities, including <a href="/facts/Phosphorylation/LXUEEeIL">phosphorylation</a>, <a href="/facts/Glycosylation/VYEeQCRz">glycosylation</a>, <a href="/facts/Myristoylation/KbEstnBu">myristoylation</a> and <a href="/facts/Palmitoylation/soDel1Xt">palmitoylation</a>.<a class="footnote-ref" id="fnref:98" href="#fn:98"><sup>98</sup></a> Similar to <a href="/facts/Mammal/phSwTzBo">mammalian</a> cells, proteins expressed are mostly <a href="/facts/Soluble/kLE9h3Jb">soluble</a>, accurately folded, and biologically active.<a class="footnote-ref" id="fnref:99" href="#fn:99"><sup>99</sup></a> However, it has slower growth rate and requires higher cost of <a href="/facts/Growth_medium/97IMkpFP">growth medium</a> than <a href="/facts/Bacteria/wC8xSCsU">bacteria</a> and <a href="/facts/Yeast/eGD24nfI">yeast</a>, and confers <a href="/facts/Toxicological/L6XHRIJH">toxicological</a> risks.<a class="footnote-ref" id="fnref:100" href="#fn:100"><sup>100</sup></a> A notable feature is the existence of elements of control that allow for the expression of secreted and <a href="/facts/Membrane/FDlaJe23">membrane</a>-bound proteins in Baculovirus-insect cells.<a class="footnote-ref" id="fnref:101" href="#fn:101"><sup>101</sup></a><a class="footnote-ref" id="fnref:102" href="#fn:102"><sup>102</sup></a> </p><p>Licensed recombinant subunit <a href="/facts/Vaccine/QcXzLug2">vaccines</a> that utilises <a href="/facts/Baculoviridae/nT603scg">baculovirus</a>-<a href="/facts/Insect/IgDNvnUL">insect</a> cells include <a href="/facts/Cervarix/kHQ2Q6Jd">Cervarix</a> (papillomavirus C-terminal truncated major capsid protein L1 types 16 and 18)<a class="footnote-ref" id="fnref:103" href="#fn:103"><sup>103</sup></a><a class="footnote-ref" id="fnref:104" href="#fn:104"><sup>104</sup></a> and <a href="/facts/Influenza_vaccine/6J8BBKN1">Flublok Quadrivalent</a> (<a href="/facts/Hemagglutinin_(influenza)/jtWVdu9k">hemagglutinin</a> (<a href="/facts/Hemagglutinin_(influenza)/jtWVdu9k">HA</a>) proteins from four strains of <a href="/facts/Influenza_viruses/3gqqgCMp">influenza viruses</a>).<a class="footnote-ref" id="fnref:105" href="#fn:105"><sup>105</sup></a> </p> <h3>Extraction and purification</h3> <p>Throughout history, extraction and <a href="/facts/Protein_purification/3q0AwnWK">purification</a> methods have evolved from standard <a href="/facts/Chromatography/2FrvPjNV">chromatographic methods</a> to the utilisation of <a href="/facts/Affinity_tags/NHmdxTVl">affinity tags</a>.<a class="footnote-ref" id="fnref:106" href="#fn:106"><sup>106</sup></a> However, the final extraction and purification process undertaken highly depends on the chosen <a href="/facts/Expression_vector/yqjSkTgE">expression system</a>. Please refer to subunit expression and synthesis for more insights. </p> <h3>Addition of adjuvants</h3> <p><a href="/facts/Immunologic_adjuvant/nMbqU16c">Adjuvants</a> are materials added to improve <a href="/facts/Immunogenicity/QVxzK4tD">immunogenicity</a> of recombinant subunit <a href="/facts/Vaccine/QcXzLug2">vaccines</a>.<a class="footnote-ref" id="fnref:107" href="#fn:107"><sup>107</sup></a> </p><p>Adjuvants increase the magnitude of adaptive response to the <a href="/facts/Vaccine/QcXzLug2">vaccine</a> and guide the activation of the most effective forms of <a href="/facts/Immunity_(medical)/vLPpzSNL">immunity</a> for each specific <a href="/facts/Pathogen/axMXtV1M">pathogen</a> (e.g. increasing generation of T cell memory).<a class="footnote-ref" id="fnref:108" href="#fn:108"><sup>108</sup></a><a class="footnote-ref" id="fnref:109" href="#fn:109"><sup>109</sup></a><a class="footnote-ref" id="fnref:110" href="#fn:110"><sup>110</sup></a><a class="footnote-ref" id="fnref:111" href="#fn:111"><sup>111</sup></a> Addition of adjuvants may confer benefits including dose sparing and stabilisation of final vaccine formulation.<a class="footnote-ref" id="fnref:112" href="#fn:112"><sup>112</sup></a><a class="footnote-ref" id="fnref:113" href="#fn:113"><sup>113</sup></a> </p><p>Appropriate adjuvants are chosen based on safety, tolerance, compatibility of antigen and <a href="/facts/Manufacturing/3qW7bcdy">manufacturing</a> considerations.<a class="footnote-ref" id="fnref:114" href="#fn:114"><sup>114</sup></a> Commonly used adjuvants for recombinant subunit <a href="/facts/Vaccine/QcXzLug2">vaccines</a> are <a href="/facts/Alum/ULAn0XRB">Alum</a> adjuvants (e.g. <a href="/facts/Aluminium_hydroxide/e0pXvDGr">aluminium hydroxide</a>), <a href="/facts/Emulsion/YMSqSCuH">Emulsions</a> (e.g. <a href="/facts/MF59/uNHX6S6Q">MF59</a>) and <a href="/facts/Liposome/l9P4LVbS">Liposomes</a> combined with <a href="/facts/Immunostimulatory/B2sAKp57">immunostimulatory</a> molecules (e.g. AS01B).<a class="footnote-ref" id="fnref:115" href="#fn:115"><sup>115</sup></a><a class="footnote-ref" id="fnref:116" href="#fn:116"><sup>116</sup></a> </p> <h3>Formulation and delivery</h3> <p><a href="/facts/Drug_delivery/vDfboXeT">Delivery systems</a> are primarily divided into polymer-based <a href="/facts/Drug_delivery/vDfboXeT">delivery systems</a> (<a href="/facts/Microspheres/bYKcPY7F">microspheres</a> and <a href="/facts/Liposome/l9P4LVbS">liposomes</a>) and live <a href="/facts/Drug_delivery/vDfboXeT">delivery systems</a> (<a href="/facts/Gram-positive_bacteria/H6WYQ17e">gram-positive bacteria</a>, <a href="/facts/Gram-negative_bacteria/S1PbVtp4">gram-negative bacteria</a> and <a href="/facts/Virus/mf88Bcbl">viruses</a>) </p> <h4>Polymer-based delivery systems</h4> <p><a href="/facts/Antigen/9JlAernG">Vaccine antigens</a> are often encapsulated within <a href="/facts/Microparticle/bYKcPY7F">microspheres</a> or <a href="/facts/Liposome/l9P4LVbS">liposomes</a>. Common microspheres made using <a href="/facts/Polylactic_acid/QHoY2H5I">Poly-lactic acid (PLA)</a><a class="footnote-ref" id="fnref:117" href="#fn:117"><sup>117</sup></a> and <a href="/facts/PLGA/2hGMeI7f">poly-lactic-co-glycolic acid (PLGA)</a><a class="footnote-ref" id="fnref:118" href="#fn:118"><sup>118</sup></a> allow for controlled <a href="/facts/Antigen/9JlAernG">antigen</a> release by degrading in vivo while <a href="/facts/Liposome/l9P4LVbS">liposomes</a> including multilamellar or unilamellar vesicles allow for prolonged release.<a class="footnote-ref" id="fnref:119" href="#fn:119"><sup>119</sup></a> </p><p>Polymer-based <a href="/facts/Drug_delivery/vDfboXeT">delivery systems</a> confer advantages such as increased resistance to degradation in <a href="/facts/Gi_tract/nK2zwqBS">GI tract</a>, controlled <a href="/facts/Antigen/9JlAernG">antigen</a> release, raised particle uptake by <a href="/facts/Immune_cells/vsDunUK0">immune cells</a> and enhanced ability to induce <a href="/facts/Cytotoxic_T_cell/e5eRg3XJ">cytotoxic T cell</a> responses.<a class="footnote-ref" id="fnref:120" href="#fn:120"><sup>120</sup></a> An example of licensed recombinant vaccine utilising <a href="/facts/Liposome/l9P4LVbS">liposomal</a> delivery is <a href="/facts/Shingrix/EgFY6JmK">Shringrix</a>. </p> <h4>Live delivery systems</h4> <p>Live <a href="/facts/Drug_delivery/vDfboXeT">delivery systems</a>, also known as <a href="/facts/Vectors_in_gene_therapy/hH43tmyn">vectors</a>, are cells modified with <a href="/facts/Ligand_(biochemistry)/44QLL4eU">ligands</a> or <a href="/facts/Antigen/9JlAernG">antigens</a> to improve the <a href="/facts/Immunogenicity/QVxzK4tD">immunogenicity</a> of recombinant subunits via altering <a href="/facts/Antigen_presentation/RMEAcYwR">antigen presentation</a>, <a href="/facts/Biodistribution/9yFxNSGP">biodistribution</a> and trafficking.<a class="footnote-ref" id="fnref:121" href="#fn:121"><sup>121</sup></a> Subunits may either be inserted within the carrier or <a href="/facts/Genetically-engineered/vwdlDR61">genetically engineered</a> to be expressed on the surface of the <a href="/facts/Vectors_in_gene_therapy/hH43tmyn">vectors</a> for efficient presentation to the <a href="/facts/Mucosal_immune_system/YQzm2TEM">mucosal immune system</a>.<a class="footnote-ref" id="fnref:122" href="#fn:122"><sup>122</sup></a> </p> <h2 id="advantages-and-disadvantages">Advantages and disadvantages</h2> <h3>Advantages</h3> <ul><li>Cannot revert to <a href="/facts/Virulence/TYmX1Fa6">virulence</a> meaning they cannot cause the disease they aim to protect against<a class="footnote-ref" id="fnref:123" href="#fn:123"><sup>123</sup></a><a class="footnote-ref" id="fnref:124" href="#fn:124"><sup>124</sup></a></li> <li>Safe for <a href="/facts/Immunocompromised/CIEujXmc">immunocompromised</a> patients<a class="footnote-ref" id="fnref:125" href="#fn:125"><sup>125</sup></a></li> <li>Can withstand changes in conditions (e.g. temperature, light exposure, humidity)<a class="footnote-ref" id="fnref:126" href="#fn:126"><sup>126</sup></a></li></ul> <h3>Disadvantages</h3> <ul><li>Reduced <a href="/facts/Immunogenicity/QVxzK4tD">immunogenicity</a> compared to <a href="/facts/Attenuated_vaccine/Gabb4afu">attenuated vaccines</a><a class="footnote-ref" id="fnref:127" href="#fn:127"><sup>127</sup></a><a class="footnote-ref" id="fnref:128" href="#fn:128"><sup>128</sup></a> <ul><li>Require <a href="/facts/Immunologic_adjuvant/nMbqU16c">adjuvants</a> to improve immunogenicity<a class="footnote-ref" id="fnref:129" href="#fn:129"><sup>129</sup></a><a class="footnote-ref" id="fnref:130" href="#fn:130"><sup>130</sup></a></li> <li>Often require multiple doses (<a href="/facts/Booster_dose/A1tv9SVq">"booster" doses</a>) to provide long-term immunity<a class="footnote-ref" id="fnref:131" href="#fn:131"><sup>131</sup></a><a class="footnote-ref" id="fnref:132" href="#fn:132"><sup>132</sup></a></li></ul></li> <li>Can be difficult to isolate the specific <a href="/facts/Antigen/9JlAernG">antigen(s)</a> which will invoke the necessary <a href="/facts/Immune_response/dtLulqIy">immune response</a><a class="footnote-ref" id="fnref:133" href="#fn:133"><sup>133</sup></a></li> <li>It is not easy to supervise conjugation chemistry which leads to noncontinuous variation<a class="footnote-ref" id="fnref:134" href="#fn:134"><sup>134</sup></a></li></ul> <h2 id="adverse-effects-and-contraindications">Adverse effects and contraindications</h2> <p>Recombinant subunit <a href="/facts/Vaccine/QcXzLug2">vaccines</a> are safe for administration.<a class="footnote-ref" id="fnref:135" href="#fn:135"><sup>135</sup></a><a class="footnote-ref" id="fnref:136" href="#fn:136"><sup>136</sup></a> However, mild local reactions, including <a href="/facts/Induration/Vkr5XpeG">induration</a> and <a href="/facts/Swelling_(medical)/Q6MI3KdH">swelling</a> of the injection site, along with <a href="/facts/Fever/waVxR2Ac">fever</a>, <a href="/facts/Fatigue/C2oo4Hvg">fatigue</a> and <a href="/facts/Headache/mdmmC9DP">headache</a> may be encountered after vaccination.<a class="footnote-ref" id="fnref:137" href="#fn:137"><sup>137</sup></a><a class="footnote-ref" id="fnref:138" href="#fn:138"><sup>138</sup></a><a class="footnote-ref" id="fnref:139" href="#fn:139"><sup>139</sup></a> Occurrence of severe <a href="/facts/Hypersensitivity/j2AWmqCD">hypersensitivity</a> reactions and <a href="/facts/Anaphylaxis/F9IDQxeL">anaphylaxis</a> is rare,<a class="footnote-ref" id="fnref:140" href="#fn:140"><sup>140</sup></a> but can possibly lead to <a href="/facts/Death/VJmq29qm">deaths</a> of individuals. <a href="/facts/Adverse_effect/vAhfbr1J">Adverse effects</a> can vary among populations depending on their <a href="/facts/Physical_health/yzPVrjTs">physical health</a> condition, age, <a href="/facts/Gender/LfjRHcJy">gender</a> and <a href="/facts/Genetics/bu8wne0A">genetic</a> predisposition.<a class="footnote-ref" id="fnref:141" href="#fn:141"><sup>141</sup></a><a class="footnote-ref" id="fnref:142" href="#fn:142"><sup>142</sup></a> </p><p>Recombinant subunit <a href="/facts/Vaccine/QcXzLug2">vaccines</a> are <a href="/facts/Contraindication/HawhU8x9">contraindicated</a> to people who have experienced <a href="/facts/Allergic_reactions/dYAVosh8">allergic reactions</a> and <a href="/facts/Anaphylaxis/F9IDQxeL">anaphylaxis</a> to <a href="/facts/Antigen/9JlAernG">antigens</a> or other components of the <a href="/facts/Vaccine/QcXzLug2">vaccines</a> previously.<a class="footnote-ref" id="fnref:143" href="#fn:143"><sup>143</sup></a><a class="footnote-ref" id="fnref:144" href="#fn:144"><sup>144</sup></a> Furthermore, precautions should be taken when administering <a href="/facts/Vaccine/QcXzLug2">vaccines</a> to people who are in <a href="/facts/Disease/55eeQlGL">diseased</a> state and during <a href="/facts/Pregnancy/vEKYGpep">pregnancy</a>,<a class="footnote-ref" id="fnref:145" href="#fn:145"><sup>145</sup></a> in which their injections should be delayed until their conditions become stable and after childbirth respectively. </p> <h2 id="licensed-vaccines">Licensed vaccines</h2> <h3>Hepatitis B</h3> <p><a href="/facts/Engerix-B/j2gQw4Sc">ENGERIX-B</a> (produced by GSK) and <a href="/facts/Recombivax_HB/j2gQw4Sc">RECOMBIVAX HB</a> (produced by merck) are two recombinant subunit <a href="/facts/Vaccine/QcXzLug2">vaccines</a> licensed for the protection against <a href="/facts/Hepatitis_B/qqPTEY3p">hepatitis B</a>. Both contain <a href="/facts/HBsAg/PBxJ0fve">HBsAg</a> harvested and purified from <i><a href="/facts/Saccharomyces_cerevisiae/sX9MGFrz">Saccharomyces cerevisiae</a></i> and are formulated as a suspension of the <a href="/facts/Antigen/9JlAernG">antigen</a> adjuvanted with <a href="/facts/Alum/ULAn0XRB">alum</a>.<a class="footnote-ref" id="fnref:146" href="#fn:146"><sup>146</sup></a><a class="footnote-ref" id="fnref:147" href="#fn:147"><sup>147</sup></a> </p><p><a href="/facts/Antibody/MX8pdTdP">Antibody</a> concentration ≥10mIU/mL against <a href="/facts/HBsAg/PBxJ0fve">HBsAg</a> are recognized as conferring protection against hepatitis B infection.<a class="footnote-ref" id="fnref:148" href="#fn:148"><sup>148</sup></a><a class="footnote-ref" id="fnref:149" href="#fn:149"><sup>149</sup></a> </p><p>It has been shown that primary 3-dose <a href="/facts/Vaccination/3SfpzPsd">vaccination</a> of healthy individuals is associated with ≥90% seroprotection rates for <a href="/facts/Engerix-B/j2gQw4Sc">ENGERIX-B</a>, despite decreasing with older age. Lower seroprotection rates are also associated with presence of underlying <a href="/facts/Chronic_condition/6CqLP41r">chronic diseases</a> and <a href="/facts/Immunodeficiency/CIEujXmc">immunodeficiency</a>. Yet, GSK HepB still has a clinically acceptable <a href="/facts/Safety_profile/4v2PDxCM">safety profile</a> in all studied populations.<a class="footnote-ref" id="fnref:150" href="#fn:150"><sup>150</sup></a> </p> <h3>Human Papillomavirus (HPV)</h3> <p><a href="/facts/Cervarix/kHQ2Q6Jd">Cervarix</a>, <a href="/facts/Gardasil/kNjp7s2z">GARDASIL</a> and <a href="/facts/Gardasil/kNjp7s2z">GARDASIL9</a> are three recombinant subunit <a href="/facts/Vaccine/QcXzLug2">vaccines</a> licensed for the protection against <a href="/facts/Human_papillomavirus_infection/7XW8mjG2">HPV</a> infection. They differ in the <a href="/facts/Strain_(biology)/xFv4QWjN">strains</a> which they protect the patients from as <a href="/facts/Cervarix/kHQ2Q6Jd">Cervarix</a> confers protection against type 16 and 18,<a class="footnote-ref" id="fnref:151" href="#fn:151"><sup>151</sup></a> <a href="/facts/Gardasil/kNjp7s2z">Gardasil</a> confers protection against type 6, 11, 16 and 18,<a class="footnote-ref" id="fnref:152" href="#fn:152"><sup>152</sup></a> and Gardasil 9 confers protection against type 6, 11, 16, 18, 31, 33, 45, 52, 58<a class="footnote-ref" id="fnref:153" href="#fn:153"><sup>153</sup></a> respectively. The <a href="/facts/Vaccine/QcXzLug2">vaccines</a> contain purified <a href="/facts/VLPs/32B60efL">VLP</a> of the major capsid L1 protein produced by recombinant <i><a href="/facts/Saccharomyces_cerevisiae/sX9MGFrz">Saccharomyces cerevisiae</a></i>. </p><p>It has been shown in a 2014 systematic quantitative review that the bivalent HPV vaccine (<a href="/facts/Cervarix/kHQ2Q6Jd">Cervarix</a>) is associated with <a href="/facts/Pain/70E79oUn">pain</a> (OR 3.29; 95% CI: 3.00–3.60), <a href="/facts/Allergy/dYAVosh8">swelling</a> (OR 3.14; 95% CI: 2.79–3.53) and <a href="/facts/Redness/gLnFAVx4">redness</a> (OR 2.41; 95% CI: 2.17–2.68) being the most frequently reported adverse effects. For Gardasil, the most frequently reported events were <a href="/facts/Pain/70E79oUn">pain</a> (OR 2.88; 95% CI: 2.42–3.43) and <a href="/facts/Allergy/dYAVosh8">swelling</a> (OR 2.65; 95% CI: 2.0–3.44).<a class="footnote-ref" id="fnref:154" href="#fn:154"><sup>154</sup></a> </p><p>Gardasil was discontinued in the U.S. on May 8, 2017, after the introduction of Gardasil 9<a class="footnote-ref" id="fnref:155" href="#fn:155"><sup>155</sup></a> and Cervarix was also voluntarily withdrawn in the U.S. on August 8, 2016.<a class="footnote-ref" id="fnref:156" href="#fn:156"><sup>156</sup></a> </p> <h3>Influenza</h3> <p><a href="/facts/Flublok_Quadrivalent/6J8BBKN1">Flublok Quadrivalent</a> is a licensed recombinant subunit <a href="/facts/Vaccine/QcXzLug2">vaccine</a> for active <a href="/facts/Immunization/f2NLoleW">immunisation</a> against <a href="/facts/Influenza/nWuFzh6L">influenza</a>. It contains <a href="/facts/Hemagglutinin_(influenza)/jtWVdu9k">HA</a> proteins of four <a href="/facts/Strain_(biology)/xFv4QWjN">strains</a> of <a href="/facts/Influenza/nWuFzh6L">influenza</a> virus purified and extracted using the <a href="/facts/Baculoviridae/nT603scg">Baculovirus</a>-<a href="/facts/Insect/IgDNvnUL">insect</a> <a href="/facts/Expression_vector/yqjSkTgE">expression system</a>. The four viral strains are standardised annually according to <a href="/facts/United_States_Public_Health_Service/utUnKRuS">United States Public Health Services (USPHS)</a> requirements.<a class="footnote-ref" id="fnref:157" href="#fn:157"><sup>157</sup></a> </p><p><a href="/facts/Flublok_Quadrivalent/6J8BBKN1">Flublok Quadrivalent</a> 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 <a href="/facts/Chills/lqjTeJ1H">chills</a> (RR = 1.33, 95% CI 1.03–1.72, three RCTs, FEM, I2 = 14%, low‐certainty evidence).<a class="footnote-ref" id="fnref:158" href="#fn:158"><sup>158</sup></a> </p> <h3>Herpes Zoster</h3> <p><a href="/facts/Shingrix/EgFY6JmK">SHINGRIX</a> is a licensed recombinant subunit <a href="/facts/Vaccine/QcXzLug2">vaccine</a> for protection against <a href="/facts/Herpes_zoster/2rEq69rr">Herpes Zoster</a>, whose risk of developing increases with decline of <a href="/facts/Varicella_zoster_virus_(VZV)/ebbSkn9U">varicella zoster virus (VZV)</a> specific <a href="/facts/Immunity_(medical)/vLPpzSNL">immunity</a>. The vaccine contains <a href="/facts/VZV/ebbSkn9U">VZV</a> gE antigen component extracted from <a href="/facts/Chinese_hamster_ovary_cell/t09KCNNc">CHO cells</a>, which is to be reconstituted with <a href="/facts/Adjuvant/jnRqeBnG">adjuvant</a> suspension AS01B.<a class="footnote-ref" id="fnref:159" href="#fn:159"><sup>159</sup></a> </p><p><a href="/facts/Systematic_review/dGvq3BGx">Systematic reviews</a> and <a href="/facts/Meta-analysis/IcfChd8z">meta-analyses</a> have been conducted on the efficacy, effectiveness and safety of <a href="/facts/Shingrix/EgFY6JmK">SHINGRIX</a> in <a href="/facts/Immunocompromised/CIEujXmc">immunocompromised</a> 18–49 year old patients and healthy adults aged 50 and over. These studies reported <a href="/facts/Humoral_immunity/qG9I4pGf">humoral</a> and <a href="/facts/Cell-mediated_immunity/vPX39rt1">cell-mediated immunity</a> rate ranged between 65.4 and 96.2% and 50.0–93.0% while efficacy in patients (18–49 yo) with <a href="/facts/Hematological_malignancies/tzyyShka">haematological malignancies</a> was estimated at 87.2% (95%CI, 44.3–98.6%) up to 13 months post-vaccination with an acceptable <a href="/facts/Safety_profile/4v2PDxCM">safety profile</a>.<a class="footnote-ref" id="fnref:160" href="#fn:160"><sup>160</sup></a><a class="footnote-ref" id="fnref:161" href="#fn:161"><sup>161</sup></a> </p> <h3>COVID-19</h3> <p><a href="/facts/Nuvaxovid/bY4ByGQz">NUVAXOVID</a> is a recombinant subunit vaccine licensed for the prevention of <a href="/facts/COVID-19/YsUgvsaX">SARS-CoV-2 infection</a>. Market authorization was issued on 20 December 2021.<a class="footnote-ref" id="fnref:162" href="#fn:162"><sup>162</sup></a> The vaccine contains the <a href="/facts/SARS-CoV-2_spike_protein/JTcbvUn2">SARS-CoV-2 spike</a> protein produced using the <a href="/facts/Baculoviridae/nT603scg">baculovirus</a> <a href="/facts/Expression_vector/yqjSkTgE">expression system</a>, which is eventually adjuvanted with the <a href="/facts/Matrix-M/7264XTly">Matrix M</a> adjuvant.<a class="footnote-ref" id="fnref:163" href="#fn:163"><sup>163</sup></a> </p> <h2 id="history">History</h2> <p>While the practice of <a href="/facts/Immunization/f2NLoleW">immunisation</a> can be traced back to the <a href="/facts/12th_century/pBmlrFfW">12th century</a>, in which ancient <a href="/facts/Chinese_people/Ft6TzPzd">Chinese</a> at that time employed the technique of <a href="/facts/Variolation/2uqzNTya">variolation</a> to confer <a href="/facts/Immunity_(medical)/vLPpzSNL">immunity</a> to <a href="/facts/Smallpox/cxNeetP4">smallpox</a> infection, the modern era of vaccination has a short history of around 200 years. It began with the <a href="/facts/Invention/P3LdUHBY">invention</a> of a vaccine by Edward Jenner in 1798 to eradicate <a href="/facts/Smallpox/cxNeetP4">smallpox</a> by injecting relatively weaker <a href="/facts/Cowpox/zzPD2Vx9">cowpox</a> virus into the human body. </p><p>The middle of the 20th century marked the golden age of vaccine science. Rapid technological advancements during this period of time enabled scientists to cultivate <a href="/facts/Cell_culture/7Qhu13D9">cell culture</a> under controlled environments in laboratories,<a class="footnote-ref" id="fnref:164" href="#fn:164"><sup>164</sup></a> subsequently giving rise to the production of vaccines against <a href="/facts/Polio/6dYyXUhE">poliomyelitis</a>, <a href="/facts/Measles/tepQCUIG">measles</a> and various <a href="/facts/Infection/182XrncP">communicable diseases</a>. Conjugated vaccines were also developed using <a href="/facts/Immunology/vylm0L8e">immunologic</a> markers including capsular <a href="/facts/Polysaccharide/lqXq2cJU">polysaccharide</a> and <a href="/facts/Protein/Jxmagu3E">proteins</a>.<a class="footnote-ref" id="fnref:165" href="#fn:165"><sup>165</sup></a> Creation of products targeting common illnesses successfully lowered infection-related <a href="/facts/Mortality_rate/s4gmxyFV">mortality</a> and reduced <a href="/facts/Public_healthcare/vwWns7cu">public healthcare</a> burden. </p><p>Emergence of <a href="/facts/Genetic_engineering_techniques/ahP1jNG1">genetic engineering techniques</a> revolutionised the creation of vaccines. By the end of the 20th century, researchers had the ability to create <a href="/facts/Recombinant_vaccines/QcXzLug2">recombinant vaccines</a> apart from traditional <a href="/facts/Whole-cell_vaccine/r8uPkr2N">whole-cell vaccine</a>, for instance <a href="/facts/Hepatitis_B_vaccine/j2gQw4Sc">Hepatitis B vaccine</a>, which uses the viral <a href="/facts/Antigen/9JlAernG">antigens</a> to initiate <a href="/facts/Immune_response/dtLulqIy">immune responses</a>.<a class="footnote-ref" id="fnref:166" href="#fn:166"><sup>166</sup></a> </p><p>As the <a href="/facts/Manufacturing/3qW7bcdy">manufacturing</a> 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 <a href="/facts/Non-communicable_disease/a3HxqDL3">non-infectious diseases</a>, in order to safeguard the health of more people. </p> <h2 id="future-directions">Future directions</h2> <p>Recombinant subunit <a href="/facts/Vaccine/QcXzLug2">vaccines</a> are used in development for <a href="/facts/Tuberculosis/ggPyovAl">tuberculosis</a>,<a class="footnote-ref" id="fnref:167" href="#fn:167"><sup>167</sup></a> <a href="/facts/Dengue_fever/Stn1FvlF">dengue fever</a>,<a class="footnote-ref" id="fnref:168" href="#fn:168"><sup>168</sup></a> <a href="/facts/Soil-transmitted_helminthiasis/T9B8v5ab">soil-transmitted helminths</a>,<a class="footnote-ref" id="fnref:169" href="#fn:169"><sup>169</sup></a> <a href="/facts/Feline_leukemia_virus/dVAoftwC">feline leukaemia</a><a class="footnote-ref" id="fnref:170" href="#fn:170"><sup>170</sup></a> and <a href="/facts/COVID-19/YsUgvsaX">COVID-19</a>.<a class="footnote-ref" id="fnref:171" href="#fn:171"><sup>171</sup></a> </p><p>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.<a class="footnote-ref" id="fnref:172" href="#fn:172"><sup>172</sup></a> </p> <h3>COVID-19</h3> <p>Research has been conducted to explore the possibility of developing a heterologous <a href="/facts/SARS-CoV/jXYCe6w5">SARS-CoV</a> receptor-binding domain (RBD) recombinant protein as a human <a href="/facts/Vaccine/QcXzLug2">vaccine</a> against <a href="/facts/COVID-19/YsUgvsaX">COVID-19</a>. The theory is supported by evidence that <a href="/facts/Convalescence/CeN2XkgS">convalescent</a> <a href="/facts/Serum_(blood)/a22tvug9">serum</a> from <a href="/facts/SARS-CoV/jXYCe6w5">SARS-CoV</a> patients have the ability to neutralise <a href="/facts/SARS-CoV-2/DxF8rDc1">SARS-CoV-2</a> (corresponding virus for <a href="/facts/COVID-19/YsUgvsaX">COVID-19</a>) and that amino acid similarity between <a href="/facts/SARS-CoV/jXYCe6w5">SARS-CoV</a> and <a href="/facts/SARS-CoV-2_spike_protein/JTcbvUn2">SARS-CoV-2 spike</a> and RBD protein is high (82%).<a class="footnote-ref" id="fnref:173" href="#fn:173"><sup>173</sup></a> </p> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>"Module 2 - Subunit vaccines". WHO Vaccine Safety Basics e-learning course. 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