请输入您要查询的百科知识：

　

词条 Hookworm vaccine
释义

  1. Mechanism of action

  2. Research

      Funding  

  3. References

  4. External links

Hookworm vaccine is a vaccine against hookworm.[1] No effective vaccine for the disease in humans has yet been developed. Hookworms, parasitic nematodes transmitted in soil, infect approximately 700 million humans, particularly in tropical regions of the world where endemic hookworms include Ancylostoma duodenale and Necator americanus. Hookworms feed on blood and those infected with hookworms may suffer from chronic anaemia and malnutrition.[1][2] Helminth infection can be effectively treated with benzimidazole drugs (such as mebendazole or albendazole), and efforts led by the World Health Organization have focused on one to three yearly de-worming doses in schools because hookworm infections with the heaviest intensities are most common in school-age children.[3] However, these drugs only eliminate existing adult parasites and re-infection can occur soon after treatment, school-based de-worming efforts do not treat adults or pre-school children, and concerns exist about drug resistance developing in hookworms against the commonly used treatments, thus a vaccine against hookworm disease is sought to provide more permanent resistance to infection.[3][6]

Hookworm infection is considered a neglected disease as it disproportionately affects poorer localities and has received little attention from pharmaceutical companies.[7]

Mechanism of action

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 immune system.[1] Successful hookworm vaccines have been developed for several animal species.[1] On the basis of prior work, human vaccine development has targeted antigens from both the larval and adult stages of the hookworm life cycle; a combined vaccine for humans that would provide more complete protection.[1] Current targets of larval proteins attenuate larval migration through host tissue; targets of adult proteins have been demonstrated to block enzymes vital to hookworm feeding.

The function of Na-ASP-2 is not currently known (though it may function as a chemotaxin mimic[1]), but it is a cysteine-rich secretory protein that is 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.[12][2][4][5][6] The class of proteins that includes Na-ASP-2, ASPs, 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, epidemiologic studies determined that high titers of circulating antibodies against ASPs are associated with lower hookworm burdens in residents of Hainan Province, China, and Minas Gerais, Brazil.[7]

Ac-APR-1 is an aspartic protease, specifically a hemoglobinase, that participates in the hookworm's digestion of hemoglobin from its blood meal[6] and is present in the adult stage of the hookworm life cycle.[1][8] Animals immunized against Ac-APR-1 exhibited a reduction in worm burden, a reduction in hemoglobin loss, and a dramatic reduction in worm fecundity.[2]

Research

Examples of antigenic targets of hookworm vaccines currently in clinical trials include Na-ASP-2 from N. americanus, Ac-APR-1 from Ancylostoma caninum, Ac'-APR-1 and Na-GST-1/Alhydroge.[9] In a clinical trial a vaccine containing recombinant Na-ASP-2 with Alhydrogel as an adjuvant was found to increase Th2 helper cells and IgE. 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.[10]

In 2014 Na-GST-1/Alhydroge completed a successful phase 1 clinical trial in Brazil.[9]

Funding

Research funding to develop hookworm vaccines has come from the Human Hookworm Vaccine Initiative,[11] a program of the Sabin Vaccine Institute and collaborations with George Washington University, the Oswaldo Cruz Foundation, the Chinese Institute of Parasitic Diseases, the Queensland Institute of Medical Research, and the London School of Hygiene and Tropical Medicine.[2][12][13] Funding for hookworm vaccine research efforts also includes funds from the Bill & Melinda Gates Foundation,[14][15] totaling in excess of $53 million,[7] and additional support from the Rockefeller Foundation, Doctors Without Borders, National Institute of Allergy and Infectious Diseases, and the March of Dimes Birth Defects Foundation.[16][13]

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.[17]

References

1. ^1 2 3 4 5 6 {{cite journal |vauthors=Diemert DJ, Bethony JM, Hotez PJ |title=Hookworm vaccines |journal=Clin. Infect. Dis. |volume=46 |issue=2 |pages=282–8 |date=January 2008 |pmid=18171264 |doi=10.1086/524070}}
2. ^1 2 3 {{cite journal |author=Devaney E |title=The End of the Line for Hookworm? An Update on Vaccine Development |journal=PLoS Med. |volume=2 |issue=10 |pages=e327 |date=October 2005 |pmid=16187734 |pmc=1240053 |doi=10.1371/journal.pmed.0020327 |url=http://dx.plos.org/10.1371/journal.pmed.0020327}} View on Wikipedia
3. ^1 {{cite journal |vauthors=Hotez PJ, Bethony J, Bottazzi ME, Brooker S, Buss P |title=Hookworm: "The Great Infection of Mankind" |journal=PLoS Med. |volume=2 |issue=3 |pages=e67 |date=March 2005 |pmid=15783256 |pmc=1069663 |doi=10.1371/journal.pmed.0020067 |url=http://dx.plos.org/10.1371/journal.pmed.0020067}}
4. ^{{cite journal |vauthors=Fujiwara RT, Bethony J, Bueno LL, etal |title=Immunogenicity of the hookworm Na-ASP-2 vaccine candidate: characterization of humoral and cellular responses after vaccination in the Sprague Dawley rat |journal=Hum Vaccin |volume=1 |issue=3 |pages=123–8 |year=2005 |pmid=17012856 |doi= 10.4161/hv.1.3.1924|url=http://www.landesbioscience.com/journals/hv/abstract.php?id=1924}}
5. ^{{cite journal |vauthors=Bethony JM, Simon G, Diemert DJ, etal |title=Randomized, placebo-controlled, double-blind trial of the Na-ASP-2 hookworm vaccine in unexposed adults |journal=Vaccine |volume=26 |issue=19 |pages=2408–17 |date=May 2008 |pmid=18396361 |doi=10.1016/j.vaccine.2008.02.049 |url=http://linkinghub.elsevier.com/retrieve/pii/S0264-410X(08)00242-9}}
6. ^{{cite journal |vauthors=Goud GN, Bottazzi ME, Zhan B, etal |title=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 |journal=Vaccine |volume=23 |issue=39 |pages=4754–64 |date=September 2005 |pmid=16054275 |doi=10.1016/j.vaccine.2005.04.040 |url=http://linkinghub.elsevier.com/retrieve/pii/S0264-410X(05)00511-6}}
7. ^{{cite journal |vauthors=Hotez PJ, Zhan B, Bethony JM, etal |title=Progress in the development of a recombinant vaccine for human hookworm disease: the Human Hookworm Vaccine Initiative |journal=Int. J. Parasitol. |volume=33 |issue=11 |pages=1245–58 |date=September 2003 |pmid=13678639 |doi=10.1016/S0020-7519(03)00158-9 |url=http://linkinghub.elsevier.com/retrieve/pii/S0020751903001589}}
8. ^1 2 {{cite journal |vauthors=Loukas A, Bethony JM, Mendez S, etal |title=Vaccination with Recombinant Aspartic Hemoglobinase Reduces Parasite Load and Blood Loss after Hookworm Infection in Dogs |journal=PLoS Med. |volume=2 |issue=10 |pages=e295 |date=October 2005 |pmid=16231975 |pmc=1240050 |doi=10.1371/journal.pmed.0020295 |url=http://dx.plos.org/10.1371/journal.pmed.0020295}}
9. ^1 {{Cite web|url=http://www.sabin.org/updates/pressreleases/phase-1-clinical-trial-human-hookworm-vaccine-successfully-completed|title=Phase 1 Clinical Trial of Human Hookworm Vaccine Successfully Completed {{!}} Sabin|website=www.sabin.org|access-date=2016-06-11}}
10. ^1 {{Cite journal|last=Diemert|first=David J.|last2=Pinto|first2=Antonio G.|last3=Freire|first3=Janaina|last4=Jariwala|first4=Amar|last5=Santiago|first5=Helton|last6=Hamilton|first6=Robert G.|last7=Periago|first7=Maria Victoria|last8=Loukas|first8=Alex|last9=Tribolet|first9=Leon|title=Generalized urticaria induced by the Na-ASP-2 hookworm vaccine: Implications for the development of vaccines against helminths|url=http://linkinghub.elsevier.com/retrieve/pii/S0091674912007026|journal=Journal of Allergy and Clinical Immunology|volume=130|issue=1|pages=169–176.e6|doi=10.1016/j.jaci.2012.04.027}}
11. ^{{cite journal |vauthors=Bottazzi ME, Brown AS |title=Model for product development of vaccines against neglected tropical diseases: a vaccine against human hookworm |journal=Expert Rev Vaccines |volume=7 |issue=10 |pages=1481–92 |date=December 2008 |pmid=19053205 |doi=10.1586/14760584.7.10.1481 |url=http://www.future-drugs.com/doi/abs/10.1586/14760584.7.10.1481?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dncbi.nlm.nih.gov}}
12. ^Human Hookworm Vaccine Initiative Overview, Sabin Vaccine Institute
13. ^1 World Health Organization, Initiative for Vaccine Research, Hookworm disease
14. ^Researchers Cite Vaccines' Potential to Break Poverty Cycle; Genomics and Innovative Partnerships are Key to Parasitic and Bacterial Vaccine Development, Infection Control Today
15. ^Sabin Vaccine Institute Receives $13.8M Gates Foundation Grant to Pursue Bivalent Hookworm Vaccination Strategy, redOrbit.com
16. ^1 2 [https://www.washingtonpost.com/wp-dyn/content/article/2006/10/10/AR2006101001309.html In Brazil, Field Trials To Treat World's Poor], Washington Post, October 11, 2006
17. ^{{cite web|url=https://www.npr.org/templates/transcript/transcript.php?storyId=4980102|title=In Brazil, a New Effort to Wipe Out Hookworm|accessdate=2011-08-28|date=2005-10-29}}

External links

  • Study of Na-ASP-2 Human Hookworm Vaccine in Healthy Adults Without Evidence of Hookworm Infection, ClinicalTrials.gov
  • Phase 1 Trial of Na-ASP-2 Hookworm Vaccine in Previously Infected Brazilian Adults, ClinicalTrials.gov
{{Vaccines}}{{DEFAULTSORT:Hookworm Vaccine}}

1 : Vaccines
随便看

　

开放百科全书收录14589846条英语、德语、日语等多语种百科知识，基本涵盖了大多数领域的百科知识，是一部内容自由、开放的电子版国际百科全书。

　

Copyright © 2023 OENC.NET All Rights Reserved
京ICP备2021023879号 更新时间：2024/11/11 11:59:37