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Peptide vaccine
open-in-new
<h2 id="history">History</h2> <p>The traditional <a href="/facts/Vaccine/QcXzLug2">vaccines</a> are the whole live or fixed pathogens. The second generation of vaccines is mainly the protein purified from the pathogen. The third generation of vaccines is the DNA or plasmid that can express the proteins of the pathogen. Peptide vaccines are the latest step in the evolution of vaccines.<a class="footnote-ref" id="fnref:3" href="#fn:3"><sup>3</sup></a> </p> <h2 id="advantages-and-disadvantages">Advantages and disadvantages</h2> <p>Compared with the traditional vaccines such as the whole fixed pathogens or protein molecules, the peptide vaccines have several advantages and disadvantages.<a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a> </p><p>Advantages: </p> <ul><li>The vaccines are fully synthesized by <a href="/facts/Chemical_synthesis/3KXsVVwC">chemical synthesis</a> and can be treated as <a href="/facts/Chemical_entity/6Pcn5HDR">chemical entity</a>.</li> <li>With more advanced solid-phase <a href="/facts/Peptide_synthesis/Upd4aqKa">peptide synthesis</a> (SPPS) using automation and microwave techniques, the production of peptides becomes more efficient.</li> <li>The vaccines do not have any biological contamination since they are chemically synthesized.</li> <li>The vaccines are water-soluble and can be kept stable under simple conditions.</li> <li>The peptides can be specially designed for specificity. A single peptide vaccine can be designed to have multiple epitopes to generate immune responses for several diseases.</li> <li>The vaccines only contain a short peptide chain, so they are less like to lead to <a href="/facts/Allergy/dYAVosh8">allergic</a> or auto-immune responses.</li></ul> <p>Disadvantages: </p> <ul><li>Poor immunogenicity.</li> <li>Unstable in cells.</li> <li>Lack of native <a href="/facts/Protein_structure/BptnTs9X">conformation</a>.</li> <li>Only effective for a limited population.</li></ul> <h2 id="epitope-design">Epitope design</h2> <p>The whole peptide vaccine is to mimic the epitope of an antigen, so epitope design is the most important stage of vaccine development and requires an accurate understanding of the amino acid sequence of the immunogenic protein interested. The designed epitope is expected to generate strong and long-period immuno-response against the pathogen. The followings are the points to consider when designing the epitope: </p> <ul><li>The non-dominant epitope could generate a stronger immune response than the dominant epitope. Ex. The antibodies from people infected by hookworm can recognize the dominant epitope of the antigen called <i><a href="/facts/Necator_americanus/b4Wsq9gp">Necator americanus</a></i> APR-1 protein, but the antibodies can't induce protection against <a href="/facts/Hookworm/vSo9fQmh">hookworm</a>. However, other non-dominant epitopes on APR-1 protein show the ability to induce the production of neutralizing antibodies against hookworm. Therefore, the non-dominant epitopes are the better candidate for peptide vaccines against hookworm infection.<a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a></li> <li>Take <a href="/facts/Hypersensitivity/j2AWmqCD">hypersensitivity</a> into consideration. Ex. Some <a href="/facts/Immunoglobulin_E/76uGAl7k">IgE</a>-inducing epitopes cause <a href="/facts/Hypersensitivity/j2AWmqCD">hypersensitivity</a> reactions after <a href="/facts/Vaccination/3SfpzPsd">vaccination</a> in humans due to the overlap with <a href="/facts/Immunoglobulin_G/cKzc83tk">IgG</a> epitopes in the Na-ASP-2 protein which is an antigen from hookworm.<a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a></li> <li>Some short peptide epitopes need elongating to maintain the native conformation. The elongated sequences can include proper <a href="/facts/Protein_secondary_structure/MMgXXbQ2">secondary structure</a>. Also, some short peptides can be stabled or cyclized together to maintain the proper conformation. Ex. <a href="/facts/B_cell/6Y1tgwwp">B-cell</a> epitopes could only have 5 amino acids. To induce an immune response, a sequence from yeast <a href="/facts/Gcn4/51tIPlYy">GCN4</a> protein is used to improve the conformation of the peptide vaccines by forming <a href="/facts/Alpha_helix/7CESPIYJ">alpha-helix</a>..<a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a></li> <li>Use <a href="/facts/Immunologic_adjuvant/nMbqU16c">adjuvants</a> associated with the epitope to induce the immune response.<a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a></li></ul> <h2 id="applications">Applications</h2> <h3>Cancer</h3> <ul><li>Gp100 peptide vaccine is studied to treat <a href="/facts/Melanoma/qdT7E97Y">melanoma</a>. To generate a greater <a href="/facts/In_vitro/evp3hAX6"><i>in</i> <i>vitro</i></a> CTL response, the peptide, gp100:209-217(210M), is modified and binds to HLA-A2*0201. After vaccination, more circulating <a href="/facts/T_cell/5z6PQ9UN">T cells</a> can recognize and kill melanoma cancer cells <i>in vitro</i>.<a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a></li> <li><a href="/facts/Rindopepimut/DT7qA8fT">Rindopepimut</a> is the epidermal <a href="/facts/Growth_factor_receptor/cKRTJQdX">growth factor receptor</a> (EGFR)-derived peptide vaccine to treat <a href="/facts/Glioblastoma/hJojdA5x">glioblastoma multiforme</a> (GBM). The 14-mer peptide is coupled with <a href="/facts/Keyhole_limpet_hemocyanin/8F9hLwgd">keyhole limpet hemocyanin</a> (KLH), which can reduce the risk of cancer.<a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a></li> <li>E75, GP2, and AE37 are three different <a href="/facts/HER2%2fneu/xue3SgcA">HER2/<i>neu</i></a>-derived single-peptide vaccines to treat breast cancer. HER2/neu usually has low expression in healthy tissues. E75 consisting of 9 amino acids is the immunodominant epitope of the HER2 protein. GP2 consisting of 9 amino acids is the subdominant epitope. Both E75 and GP2 stimulate the <a href="/facts/T_helper_cell/nhwAYkDj">CD8+ lymphocytes</a> but GP2 has a lower affinity than E75. AE37 stimulates <a href="/facts/T_helper_cell/nhwAYkDj">CD4+ lymphocytes</a>.<a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a></li></ul> <h3>Other common diseases</h3> <ul><li><a href="/facts/EpiVacCorona/3hKs3vkC">EpiVacCorona</a>, a peptide-based vaccine against <a href="/facts/COVID-19_vaccine/obToxWTT">COVID-19</a>.</li> <li>IC41 is a peptide vaccine candidate against the <a href="/facts/Hepatitis_C_virus/DFUwAzlB">Hepatitis C virus</a>. It consists of five synthetic peptides along with the synthetic adjuvant called poly-l-arginine.<a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a></li> <li>Multimeric-001 is the most efficient peptide vaccine candidate against <a href="/facts/Influenza/nWuFzh6L">influenza</a>. It contains B- and T-cell epitopes from <a href="/facts/Hemagglutinin/1PphF1Ut">Hemagglutinin</a>. Matrix I and <a href="/facts/Nucleoprotein/S07sU6hq">nucleoprotein</a> are combined into a single recombinantly-expressed polypeptide.<a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a><a class="footnote-ref" id="fnref:14" href="#fn:14"><sup>14</sup></a></li> <li><a href="/facts/Alzheimer%2527s_disease/w7Ad6tdg">Alzheimer</a> peptide vaccines: CAD106,<a class="footnote-ref" id="fnref:15" href="#fn:15"><sup>15</sup></a> UB311,<a class="footnote-ref" id="fnref:16" href="#fn:16"><sup>16</sup></a> Lu, AF20513,<a class="footnote-ref" id="fnref:17" href="#fn:17"><sup>17</sup></a> ABvac40,<a class="footnote-ref" id="fnref:18" href="#fn:18"><sup>18</sup></a> ACI-35,<a class="footnote-ref" id="fnref:19" href="#fn:19"><sup>19</sup></a> AADvac-1.<a class="footnote-ref" id="fnref:20" href="#fn:20"><sup>20</sup></a></li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Skwarczynski M, Toth I (February 2016). "Peptide-based synthetic vaccines". 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