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Hookworm vaccine
open-in-new
<h2 id="vaccine-targets">Vaccine targets</h2> <p>Hookworm infections in humans can last for several years, and re-infection can occur very shortly after treatment, suggesting that hookworms effectively evade—and may interrupt or modulate—the host <a href="/facts/Immune_system/HRCTf1pb">immune system</a>.<a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a> Successful hookworm vaccines have been developed for several animal species.<a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a> On the basis of prior work, human vaccine development has targeted <a href="/facts/Antigen/9JlAernG">antigens</a> from both the larval and adult stages of the hookworm life cycle; a combined vaccine for humans that would provide more complete protection.<a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a> Current targets of larval proteins attenuate larval migration through host tissue; targets of adult proteins have been demonstrated to block <a href="/facts/Enzyme/DSI1Fh7y">enzymes</a> vital to hookworm feeding. </p> <p class="note">Antigen nomenclature: the first two italicized letters are abbreviated from the <a href="/facts/Binomial_name/jgBqAhPv">binomial name</a> of the worm species: <i>Na</i> is <i>Necator americanus</i>, <i>Ac</i> is <i><a href="/facts/Ancylostoma_caninum/odpIs1sG">Ancylostoma caninum</a></i>. The rest is the gene name.</p> <p>The "ASP" (ancylostoma secreted protein) proteins are <a href="/facts/Cysteine-rich_secretory_protein/duNAQxQ1">cysteine-rich secretory proteins</a>. They are promising vaccine candidates based on previous vaccine studies in sheep, guinea pigs, cattle, and mice, which have demonstrated inhibition of hookworm larval migration. Furthermore, <a href="/facts/Epidemiology/wgTmxoMA">epidemiologic studies</a> determined that high titers of circulating antibodies against ASPs are associated with lower hookworm burdens in residents of <a href="/facts/Hainan_Province/wUWoHo1V">Hainan Province</a>, <a href="/facts/China/lTjIXY5p">China</a>, and <a href="/facts/Minas_Gerais/73LdwKnD">Minas Gerais</a>, <a href="/facts/Brazil/QHkG46GL">Brazil</a>.<a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a> The function of <i>Na</i>-ASP-2 (<a href="https://www.uniprot.org/uniprot/Q7Z1H1">Q7Z1H1</a>) is not currently known (though it may function as a <a href="/facts/Chemotaxin/hYPRdPTk">chemotaxin</a> mimic<a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a>), but it is known to be released during parasite entry into the host. It may have some function in the transition from the larval environment stage of the hookworm life-cycle to an adult parasitic existence and tissue migration.<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><a class="footnote-ref" id="fnref:15" href="#fn:15"><sup>15</sup></a><a class="footnote-ref" id="fnref:16" href="#fn:16"><sup>16</sup></a><a class="footnote-ref" id="fnref:17" href="#fn:17"><sup>17</sup></a> </p><p>The "APR" proteins are <a href="/facts/Aspartic_protease/TSywUn4P">aspartic proteases</a>. <i>Ac</i>-APR-1 and <i>Na</i>-APR-1<a class="footnote-ref" id="fnref:18" href="#fn:18"><sup>18</sup></a> specifically participate in the hookworm's digestion of <a href="/facts/Hemoglobin/RsD1MzYA">hemoglobin</a> from its blood meal<a class="footnote-ref" id="fnref:19" href="#fn:19"><sup>19</sup></a> and are present in the adult stage of the hookworm life cycle.<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> Animals immunized against <i>Ac</i>-APR-1 exhibited a reduction in worm burden, a reduction in hemoglobin loss, and a dramatic reduction in worm <a href="/facts/Fecundity/e0oMColj">fecundity</a>.<a class="footnote-ref" id="fnref:22" href="#fn:22"><sup>22</sup></a> </p><p>The "GST" proteins are <a href="/facts/Glutathione_S-transferase/4Nfd68PE">glutathione S-transferases</a>. <i>Na</i>-GST-1 (<a href="https://www.uniprot.org/uniprot/D3U1A5">D3U1A5</a>) plays a role in the worm's digestion of hemoglobin; specifically, it serves to protect the worm from <a href="/facts/Heme/fRhyJAAb">heme</a> molecules released by digestion.<a class="footnote-ref" id="fnref:23" href="#fn:23"><sup>23</sup></a> </p> <h2 id="research">Research</h2> <p>Examples of antigenic targets of hookworm vaccines currently in <a href="/facts/Clinical_trial/q8LMr832">clinical trials</a> include <i>Na</i>-ASP-2, <i>Ac</i>-APR-1, <i>Na</i>-APR-1, and <i>Na</i>-GST-1.<a class="footnote-ref" id="fnref:24" href="#fn:24"><sup>24</sup></a> </p><p>In a clinical trial a vaccine containing recombinant Na-ASP-2 with <a href="/facts/Aluminium_hydroxide/e0pXvDGr">Aluminium hydroxide</a> (Alhydrogel) as an <a href="/facts/Adjuvant/jnRqeBnG">adjuvant</a> was found to increase <a href="/facts/T_helper_cell/nhwAYkDj">Th2 helper cells</a> and <a href="/facts/Immunoglobulin_E/76uGAl7k">IgE</a>. Both the Th2 helper cells and IgE antibody are important players in recognition and immunoregulation against parasites. The vaccine containing recombinant Na-ASP-2 resulted in significantly decreased risk of a hookworm infection.<a class="footnote-ref" id="fnref:25" href="#fn:25"><sup>25</sup></a> </p><p>In 2014, <i>Na</i>-GST-1 with Alhydrogel adjuvant completed a successful phase 1 clinical trial in Brazil. In 2017, it completed a successful phase 1 trial in the US.<a class="footnote-ref" id="fnref:26" href="#fn:26"><sup>26</sup></a> </p> <h3>Funding</h3> <p>Research funding to develop hookworm vaccines has come from the Human Hookworm Vaccine Initiative,<a class="footnote-ref" id="fnref:27" href="#fn:27"><sup>27</sup></a> a program of the <a href="/facts/Sabin_Vaccine_Institute/g5NQUVEM">Sabin Vaccine Institute</a> and collaborations with <a href="/facts/George_Washington_University/RBAg9f0r">George Washington University</a>, the <a href="/facts/Oswaldo_Cruz_Foundation/2WgeqIWe">Oswaldo Cruz Foundation</a>, the <a href="/facts/Chinese_Institute_of_Parasitic_Diseases/QykWGTTm">Chinese Institute of Parasitic Diseases</a>, the <a href="/facts/Queensland_Institute_of_Medical_Research/jnfPF59G">Queensland Institute of Medical Research</a>, and the <a href="/facts/London_School_of_Hygiene_and_Tropical_Medicine/RgroENaV">London School of Hygiene and Tropical Medicine</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><a class="footnote-ref" id="fnref:30" href="#fn:30"><sup>30</sup></a> Funding for hookworm vaccine research efforts also includes funds from the <a href="/facts/Bill_%2526_Melinda_Gates_Foundation/IW7prjCH">Bill & Melinda Gates Foundation</a> totaling in excess of $53 million,<a class="footnote-ref" id="fnref:31" href="#fn:31"><sup>31</sup></a> and additional support from the <a href="/facts/Rockefeller_Foundation/jdNMyMYI">Rockefeller Foundation</a>, <a href="/facts/Doctors_Without_Borders/aWHStTIt">Doctors Without Borders</a>, <a href="/facts/National_Institute_of_Allergy_and_Infectious_Diseases/PD8bQnvS">National Institute of Allergy and Infectious Diseases</a>, and the <a href="/facts/March_of_Dimes_Birth_Defects_Foundation/U7zHXHBC">March of Dimes Birth Defects Foundation</a>.<a class="footnote-ref" id="fnref:32" href="#fn:32"><sup>32</sup></a><a class="footnote-ref" id="fnref:33" href="#fn:33"><sup>33</sup></a> </p><p>The government of Brazil, where hookworm is still endemic in some poorer areas, has promised to manufacture a vaccine if one can be proven effective.<a class="footnote-ref" id="fnref:34" href="#fn:34"><sup>34</sup></a> </p> <h2 id="external-links">External links</h2> <ul><li><a href="https://clinicaltrials.gov/ct2/show/NCT00120081">Study of Na-ASP-2 Human Hookworm Vaccine in Healthy Adults Without Evidence of Hookworm Infection</a>, <a href="/facts/ClinicalTrials.gov/X6WVgItm">ClinicalTrials.gov</a></li> <li><a href="https://clinicaltrials.gov/ct2/show/NCT00473967">Phase 1 Trial of Na-ASP-2 Hookworm Vaccine in Previously Infected Brazilian Adults</a>, <a href="/facts/ClinicalTrials.gov/X6WVgItm">ClinicalTrials.gov</a></li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Diemert DJ, Bethony JM, Hotez PJ (January 2008). "Hookworm vaccines". Clin. Infect. Dis. 46 (2): 282–8. doi:10.1086/524070. PMID 18171264. <a href="https://doi.org/10.1086%2F524070" target="_blank">https://doi.org/10.1086%2F524070</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Diemert DJ, Bethony JM, Hotez PJ (January 2008). "Hookworm vaccines". Clin. Infect. Dis. 46 (2): 282–8. doi:10.1086/524070. PMID 18171264. <a href="https://doi.org/10.1086%2F524070" target="_blank">https://doi.org/10.1086%2F524070</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Devaney E (October 2005). "The End of the Line for Hookworm? An Update on Vaccine Development". PLOS Med. 2 (10): e327. doi:10.1371/journal.pmed.0020327. PMC 1240053. PMID 16187734. View on Wikipedia <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1240053" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1240053</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>Hotez PJ, Bethony J, Bottazzi ME, Brooker S, Buss P (March 2005). "Hookworm: "The Great Infection of Mankind"". PLOS Med. 2 (3): e67. doi:10.1371/journal.pmed.0020067. PMC 1069663. PMID 15783256. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1069663" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1069663</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Hotez PJ, Bethony J, Bottazzi ME, Brooker S, Buss P (March 2005). "Hookworm: "The Great Infection of Mankind"". PLOS Med. 2 (3): e67. doi:10.1371/journal.pmed.0020067. PMC 1069663. PMID 15783256. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1069663" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1069663</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>Loukas A, Bethony JM, Mendez S, et al. (October 2005). "Vaccination with Recombinant Aspartic Hemoglobinase Reduces Parasite Load and Blood Loss after Hookworm Infection in Dogs". PLOS Med. 2 (10): e295. doi:10.1371/journal.pmed.0020295. PMC 1240050. PMID 16231975. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1240050" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1240050</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>In Brazil, Field Trials To Treat World's Poor, Washington Post, October 11, 2006 <a href="https://www.washingtonpost.com/wp-dyn/content/article/2006/10/10/AR2006101001309.html" target="_blank">https://www.washingtonpost.com/wp-dyn/content/article/2006/10/10/AR2006101001309.html</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>Diemert DJ, Bethony JM, Hotez PJ (January 2008). "Hookworm vaccines". Clin. Infect. Dis. 46 (2): 282–8. doi:10.1086/524070. PMID 18171264. <a href="https://doi.org/10.1086%2F524070" target="_blank">https://doi.org/10.1086%2F524070</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>Diemert DJ, Bethony JM, Hotez PJ (January 2008). "Hookworm vaccines". Clin. Infect. Dis. 46 (2): 282–8. doi:10.1086/524070. PMID 18171264. <a href="https://doi.org/10.1086%2F524070" target="_blank">https://doi.org/10.1086%2F524070</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>Diemert DJ, Bethony JM, Hotez PJ (January 2008). "Hookworm vaccines". Clin. Infect. Dis. 46 (2): 282–8. doi:10.1086/524070. PMID 18171264. <a href="https://doi.org/10.1086%2F524070" target="_blank">https://doi.org/10.1086%2F524070</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>Hotez PJ, Zhan B, Bethony JM, et al. (September 2003). "Progress in the development of a recombinant vaccine for human hookworm disease: the Human Hookworm Vaccine Initiative". Int. J. Parasitol. 33 (11): 1245–58. doi:10.1016/S0020-7519(03)00158-9. PMID 13678639. S2CID 1741159. <a href="https://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1000&context=cbmemeagher" target="_blank">https://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1000&context=cbmemeagher</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> <li id="fn:12"><p>Diemert DJ, Bethony JM, Hotez PJ (January 2008). "Hookworm vaccines". Clin. Infect. Dis. 46 (2): 282–8. doi:10.1086/524070. PMID 18171264. <a href="https://doi.org/10.1086%2F524070" target="_blank">https://doi.org/10.1086%2F524070</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></p></li> <li id="fn:13"><p>Devaney E (October 2005). "The End of the Line for Hookworm? An Update on Vaccine Development". PLOS Med. 2 (10): e327. doi:10.1371/journal.pmed.0020327. PMC 1240053. PMID 16187734. View on Wikipedia <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1240053" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1240053</a> <a href="#fnref:13" class="footnote-back-ref">↩</a></p></li> <li id="fn:14"><p>Diemert, David J.; Pinto, Antonio G.; Freire, Janaina; Jariwala, Amar; Santiago, Helton; Hamilton, Robert G.; Periago, Maria Victoria; Loukas, Alex; Tribolet, Leon (2012). "Generalized urticaria induced by the Na-ASP-2 hookworm vaccine: Implications for the development of vaccines against helminths". Journal of Allergy and Clinical Immunology. 130 (1): 169–176.e6. doi:10.1016/j.jaci.2012.04.027. PMID 22633322. <a href="https://doi.org/10.1016%2Fj.jaci.2012.04.027" target="_blank">https://doi.org/10.1016%2Fj.jaci.2012.04.027</a> <a href="#fnref:14" class="footnote-back-ref">↩</a></p></li> <li id="fn:15"><p>Fujiwara RT, Bethony J, Bueno LL, et al. (2005). "Immunogenicity of the hookworm Na-ASP-2 vaccine candidate: characterization of humoral and cellular responses after vaccination in the Sprague Dawley rat". Hum Vaccin. 1 (3): 123–8. doi:10.4161/hv.1.3.1924. PMID 17012856. S2CID 1605830. <a href="http://www.landesbioscience.com/journals/hv/abstract.php?id=1924" target="_blank">http://www.landesbioscience.com/journals/hv/abstract.php?id=1924</a> <a href="#fnref:15" class="footnote-back-ref">↩</a></p></li> <li id="fn:16"><p>Bethony JM, Simon G, Diemert DJ, et al. (May 2008). "Randomized, placebo-controlled, double-blind trial of the Na-ASP-2 hookworm vaccine in unexposed adults". Vaccine. 26 (19): 2408–17. doi:10.1016/j.vaccine.2008.02.049. PMID 18396361. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:16" class="footnote-back-ref">↩</a></p></li> <li id="fn:17"><p>Goud GN, Bottazzi ME, Zhan B, et al. (September 2005). "Expression of the Necator americanus hookworm larval antigen Na-ASP-2 in Pichia pastoris and purification of the recombinant protein for use in human clinical trials". Vaccine. 23 (39): 4754–64. doi:10.1016/j.vaccine.2005.04.040. PMID 16054275. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:17" class="footnote-back-ref">↩</a></p></li> <li id="fn:18"><p>Pearson, Mark S.; Pickering, Darren A.; Tribolet, Leon; Cooper, Leanne; Mulvenna, Jason; Oliveira, Luciana M.; Bethony, Jeffrey M.; Hotez, Peter J.; Loukas, Alex (15 May 2010). "Neutralizing Antibodies to the Hookworm Hemoglobinase Na -APR-1: Implications for a Multivalent Vaccine against Hookworm Infection and Schistosomiasis". The Journal of Infectious Diseases. 201 (10): 1561–1569. doi:10.1086/651953. PMID 20367477. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:18" class="footnote-back-ref">↩</a></p></li> <li id="fn:19"><p>Loukas A, Bethony JM, Mendez S, et al. (October 2005). "Vaccination with Recombinant Aspartic Hemoglobinase Reduces Parasite Load and Blood Loss after Hookworm Infection in Dogs". PLOS Med. 2 (10): e295. doi:10.1371/journal.pmed.0020295. PMC 1240050. PMID 16231975. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1240050" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1240050</a> <a href="#fnref:19" class="footnote-back-ref">↩</a></p></li> <li id="fn:20"><p>Diemert DJ, Bethony JM, Hotez PJ (January 2008). "Hookworm vaccines". Clin. Infect. Dis. 46 (2): 282–8. doi:10.1086/524070. PMID 18171264. <a href="https://doi.org/10.1086%2F524070" target="_blank">https://doi.org/10.1086%2F524070</a> <a href="#fnref:20" class="footnote-back-ref">↩</a></p></li> <li id="fn:21"><p>Loukas A, Bethony JM, Mendez S, et al. (October 2005). "Vaccination with Recombinant Aspartic Hemoglobinase Reduces Parasite Load and Blood Loss after Hookworm Infection in Dogs". PLOS Med. 2 (10): e295. doi:10.1371/journal.pmed.0020295. PMC 1240050. PMID 16231975. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1240050" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1240050</a> <a href="#fnref:21" class="footnote-back-ref">↩</a></p></li> <li id="fn:22"><p>Devaney E (October 2005). "The End of the Line for Hookworm? An Update on Vaccine Development". PLOS Med. 2 (10): e327. doi:10.1371/journal.pmed.0020327. PMC 1240053. PMID 16187734. View on Wikipedia <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1240053" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1240053</a> <a href="#fnref:22" class="footnote-back-ref">↩</a></p></li> <li id="fn:23"><p>Diemert, David J.; Freire, Janaína; Valente, Vanderson; Fraga, Carlos Geraldo; Talles, Frederico; Grahek, Shannon; Campbell, Doreen; Jariwala, Amar; Periago, Maria Victoria; Enk, Martin; Gazzinelli, Maria Flávia; Bottazzi, Maria Elena; Hamilton, Robert; Brelsford, Jill; Yakovleva, Anna; Li, Guangzhao; Peng, Jin; Correa-Oliveira, Rodrigo; Hotez, Peter; Bethony, Jeffrey (2 May 2017). "Safety and immunogenicity of the Na-GST-1 hookworm vaccine in Brazilian and American adults". PLOS Neglected Tropical Diseases. 11 (5): e0005574. doi:10.1371/journal.pntd.0005574. PMC 5441635. PMID 28464026. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5441635" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5441635</a> <a href="#fnref:23" class="footnote-back-ref">↩</a></p></li> <li id="fn:24"><p>Diemert, David J.; Freire, Janaína; Valente, Vanderson; Fraga, Carlos Geraldo; Talles, Frederico; Grahek, Shannon; Campbell, Doreen; Jariwala, Amar; Periago, Maria Victoria; Enk, Martin; Gazzinelli, Maria Flávia; Bottazzi, Maria Elena; Hamilton, Robert; Brelsford, Jill; Yakovleva, Anna; Li, Guangzhao; Peng, Jin; Correa-Oliveira, Rodrigo; Hotez, Peter; Bethony, Jeffrey (2 May 2017). "Safety and immunogenicity of the Na-GST-1 hookworm vaccine in Brazilian and American adults". PLOS Neglected Tropical Diseases. 11 (5): e0005574. doi:10.1371/journal.pntd.0005574. PMC 5441635. PMID 28464026. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5441635" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5441635</a> <a href="#fnref:24" class="footnote-back-ref">↩</a></p></li> <li id="fn:25"><p>Diemert, David J.; Pinto, Antonio G.; Freire, Janaina; Jariwala, Amar; Santiago, Helton; Hamilton, Robert G.; Periago, Maria Victoria; Loukas, Alex; Tribolet, Leon (2012). "Generalized urticaria induced by the Na-ASP-2 hookworm vaccine: Implications for the development of vaccines against helminths". Journal of Allergy and Clinical Immunology. 130 (1): 169–176.e6. doi:10.1016/j.jaci.2012.04.027. PMID 22633322. <a href="https://doi.org/10.1016%2Fj.jaci.2012.04.027" target="_blank">https://doi.org/10.1016%2Fj.jaci.2012.04.027</a> <a href="#fnref:25" class="footnote-back-ref">↩</a></p></li> <li id="fn:26"><p>Diemert, David J.; Freire, Janaína; Valente, Vanderson; Fraga, Carlos Geraldo; Talles, Frederico; Grahek, Shannon; Campbell, Doreen; Jariwala, Amar; Periago, Maria Victoria; Enk, Martin; Gazzinelli, Maria Flávia; Bottazzi, Maria Elena; Hamilton, Robert; Brelsford, Jill; Yakovleva, Anna; Li, Guangzhao; Peng, Jin; Correa-Oliveira, Rodrigo; Hotez, Peter; Bethony, Jeffrey (2 May 2017). "Safety and immunogenicity of the Na-GST-1 hookworm vaccine in Brazilian and American adults". PLOS Neglected Tropical Diseases. 11 (5): e0005574. doi:10.1371/journal.pntd.0005574. PMC 5441635. PMID 28464026. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5441635" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5441635</a> <a href="#fnref:26" class="footnote-back-ref">↩</a></p></li> <li id="fn:27"><p>Bottazzi ME, Brown AS (December 2008). "Model for product development of vaccines against neglected tropical diseases: a vaccine against human hookworm". Expert Rev Vaccines. 7 (10): 1481–92. doi:10.1586/14760584.7.10.1481. PMID 19053205. S2CID 32681982. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:27" class="footnote-back-ref">↩</a></p></li> <li id="fn:28"><p>Devaney E (October 2005). "The End of the Line for Hookworm? An Update on Vaccine Development". PLOS Med. 2 (10): e327. doi:10.1371/journal.pmed.0020327. PMC 1240053. PMID 16187734. View on Wikipedia <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1240053" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1240053</a> <a href="#fnref:28" class="footnote-back-ref">↩</a></p></li> <li id="fn:29"><p>Human Hookworm Vaccine Initiative Overview Archived 2009-05-19 at the Wayback Machine, Sabin Vaccine Institute <a href="http://sabin.org/vaccine-development/vaccines/hookworm" target="_blank">http://sabin.org/vaccine-development/vaccines/hookworm</a> <a href="#fnref:29" class="footnote-back-ref">↩</a></p></li> <li id="fn:30"><p>World Health Organization, Initiative for Vaccine Research, Hookworm disease <a href="/wiki/World_Health_Organization" target="_blank">/wiki/World_Health_Organization</a> <a href="#fnref:30" class="footnote-back-ref">↩</a></p></li> <li id="fn:31"><p>In Brazil, Field Trials To Treat World's Poor, Washington Post, October 11, 2006 <a href="https://www.washingtonpost.com/wp-dyn/content/article/2006/10/10/AR2006101001309.html" target="_blank">https://www.washingtonpost.com/wp-dyn/content/article/2006/10/10/AR2006101001309.html</a> <a href="#fnref:31" class="footnote-back-ref">↩</a></p></li> <li id="fn:32"><p>In Brazil, Field Trials To Treat World's Poor, Washington Post, October 11, 2006 <a href="https://www.washingtonpost.com/wp-dyn/content/article/2006/10/10/AR2006101001309.html" target="_blank">https://www.washingtonpost.com/wp-dyn/content/article/2006/10/10/AR2006101001309.html</a> <a href="#fnref:32" class="footnote-back-ref">↩</a></p></li> <li id="fn:33"><p>World Health Organization, Initiative for Vaccine Research, Hookworm disease <a href="/wiki/World_Health_Organization" target="_blank">/wiki/World_Health_Organization</a> <a href="#fnref:33" class="footnote-back-ref">↩</a></p></li> <li id="fn:34"><p>"In Brazil, a New Effort to Wipe Out Hookworm". NPR. 2005-10-29. Retrieved 2011-08-28. <a href="https://www.npr.org/templates/transcript/transcript.php?storyId=4980102" target="_blank">https://www.npr.org/templates/transcript/transcript.php?storyId=4980102</a> <a href="#fnref:34" class="footnote-back-ref">↩</a></p></li> </ol>