DOCSLIB.ORG

Vaccination with Recombinant Aspartic Hemoglobinase Reduces Parasitic Load and Blood Loss After Hookworm Infection in Dogs

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Vaccination with Recombinant Aspartic Hemoglobinase Reduces Parasitic Load and Blood Loss After Hookworm Infection in Dogs Open access, freely available online PLoS MEDICINE Vaccination with Recombinant Aspartic Hemoglobinase Reduces Parasite Load and Blood Loss after Hookworm Infection in Dogs Alex Loukas1*, Jeffrey M. Bethony2, Susana Mendez2, Ricardo T. Fujiwara2, Gaddam Narsa Goud2, Najju Ranjit1, Bin Zhan2, Karen Jones2, Maria Elena Bottazzi2, Peter J. Hotez2* 1 Division of Infectious Diseases and Immunology, Queensland Institute of Medical Research, Brisbane, Queensland, Australia, 2 Department of Microbiology and Tropical Medicine, The George Washington University Medical Center, Washington, District of Columbia, United States of America Competing Interests: The authors have declared that no competing ABSTRACT interests exist. Background Author Contributions: AL, JMB, MEB, and PJH designed the study. Hookworms infect 730 million people in developing countries where they are a leading cause AL, RTF, GNG, NR, BZ, performed of intestinal blood loss and iron-deficiency anemia. At the site of attachment to the host, adult experiments. AL, PJH, JMB, SM, and hookworms ingest blood and lyse the erythrocytes to release hemoglobin. The parasites KJ analyzed the data. AL, PJH, JMB, and SM contributed to writing the subsequently digest hemoglobin in their intestines using a cascade of proteolysis that begins paper. with the Ancylostoma caninum aspartic protease 1, APR-1. Academic Editor: Maria Yazdanbakhsh, Leiden University Methods and Findings Medical Center, the Netherlands Citation: Loukas A, Bethony JM, We show that vaccination of dogs with recombinant Ac-APR-1 induced antibody and cellular Mendez S, Fujiwara RT, Goud GN, et responses and resulted in significantly reduced hookworm burdens (p ¼ 0.056) and fecal egg al. (2005) Vaccination with counts (p ¼ 0.018) in vaccinated dogs compared to control dogs after challenge with infective recombinant aspartic hemoglobinase reduces parasite larvae of A. caninum. Most importantly, vaccinated dogs were protected against blood loss (p ¼ load and blood loss after hookworm 0.049) and most did not develop anemia, the major pathologic sequela of hookworm disease. infection. PLoS Med 2(10): e295. IgG from vaccinated animals decreased the catalytic activity of the recombinant enzyme in vitro Received: April 8, 2005 and the antibody bound in situ to the intestines of worms recovered from vaccinated dogs, Accepted: July 13, 2005 implying that the vaccine interferes with the parasite’s ability to digest blood. Published: October 4, 2005 DOI: Conclusion 10.1371/journal.pmed.0020295 To the best of our knowledge, this is the first report of a recombinant vaccine from a Copyright: Ó 2005 Loukas et al. This is an open-access article distributed hematophagous parasite that significantly reduces both parasite load and blood loss, and it under the terms of the Creative supports the development of APR-1 as a human hookworm vaccine. Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abbreviations: APR-1, Ancylostoma caninum aspartic protease 1; AS03, GlaxoSmithKline Adjuvant System 01; ELISA, enzyme-linked immunosorbent assay; epg, eggs per gram of feces; Hb, hemoglobin; L3, third stage larvae *To whom correspondence should be addressed. E-mail: alex.loukas@ qimr.edu.au (AL); mtmpjh@gwumc. edu (PJH) PLoS Medicine | www.plosmedicine.org1008 October 2005 | Volume 2 | Issue 10 | e295 Vaccination with Hookworm Hemoglobinase Introduction and particularly fetal, Hb demands are considerable, render- ing these populations most vulnerable to the parasite [1]. Hookworms infect more than 700 million people in Here we describe vaccination of dogs with the aspartic tropical and subtropical regions of the world. The major hemoglobinase of A. caninum, Ac-APR-1 [21,23] and show that species infecting humans are Necator americanus and Ancylos- vaccination resulted in the production of neutralizing anti- toma duodenale. The parasites feed on blood, causing iron- bodies, significantly reduced egg counts, and significantly deficiency anemia, and as such, are a major cause of disease reduced adult worm burdens. Most importantly, Hb levels of burden in developing countries [1]. Unlike other human vaccinated dogs were significantly higher than those of dogs helminthiases, worm burdens do not generally decrease with that were vaccinated with adjuvant alone after parasite age; in fact, recent findings revealed that the heaviest worm challenge. These data show that aspartic hemoglobinases, burdens are found among the elderly [2,3]. Whereas particularly APR-1, are efficacious vaccines against canine anthelminthic chemotherapy with benzimidazole drugs is hookworm disease, providing strong support for further effective in eliminating existing adult parasites, re-infection investigation and development of APR-1 as a recombinant occurs rapidly after treatment [4], making a vaccine against vaccine against human hookworm disease. hookworm disease a desirable goal. Canines can be successfully vaccinated against infection Methods with the dog hookworm, Ancylostoma caninum, by immunization with third-stage infective larvae (L3) that have been attenu- Expression of Recombinant Ac-APR-1 in Pichia pastoris ated with ionizing radiation [5–7]. Subsequently, varying levels The entire open reading frame of Ac-APR-1 encoding the of vaccine efficacy have been reported for the major antigens zymogen (spanning Ser-17 to the C-terminal Phe-446) but secreted by hookworm L3 using hamsters [8,9] and dogs [10]. excluding the predicted signal peptide was cloned into the Despite obtaining encouraging levels of protection with larval expression vector pPIC-Za (Invitrogen, Carlsbad, California, antigens, only partial reductions in parasite load (fecal egg United States) using the XbaI and EcoRI sites. Yeast, P. pastoris counts and adult worm burdens) were reported. Moreover, X 33, was transformed with the vector encoding the Ac-APR-1 protective antigens from the larval stage are only expressed by zymogen as recommended by the manufacturer (Invitrogen) L3, and not adult worms, rendering antibodies against these with modifications. Protein disulfide isomerase (PDI) gene in L3 secretions useless against parasites that have successfully the vector pPIC3.5 (a gift from Mehmet Inan, University of reached adulthood in the gut and begun to feed on blood. We Nebraska, Lincoln, Nebraska, United States) was cut with SacI and transformed into P. pastoris X 33 cells which were already therefore suggest that an ideal hookworm vaccine would transformed with Ac-apr-1 following the manufacturer’s require a cocktail of two recombinant proteins, one targeting instructions. Eight transformed colonies were picked from the infective larva and the second targeting the blood-feeding YPD plates containing Geneticin (0.5–1.0 mgÁmlÀ1)and adult stage of the parasite [11]. Zeocin (1.0 mgÁmlÀ1) and tested for Ac-APR-1 expression Of the different families of proteins expressed by blood- following the manufacturer’s instructions. The highest feeding parasitic helminths, proteolytic enzymes have shown expressing colony was selected and transferred to suspension promise as intervention targets for vaccine development culture in flasks containing BMG medium (buffered minimal [12,13]. Proteases are pivotal for a parasitic existence, glycerol: 1.34% yeast nitrogen base, 0.00004% d-biotin, 1% w/ mediating fundamental physiologic processes such as molting, v glycerol, and 100 mM potassium phosphate, [pH 6.0]). tissue invasion, feeding, embryogenesis, and evasion of host Suspension cultures were then transferred to a Bioflo 3000 immune responses [12,14]. Parasite extracts enriched for fermentor (New Brunswick Scientific, Edison, New Jersey, proteases protect sheep against the blood-feeding nematodes United States) utilizing a 5-l vessel as described [8]. The Haemonchus contortus [15–18] and Ostertagia ostertagi [19]; how- recombinant protein was secreted into culture medium and ever, significant protective efficacy has not been shown with a affinity purified on nickel-agarose as described elsewhere [8]. purified recombinant protease from nematodes of livestock. Progress of purification was monitored using SDS-PAGE gels Hookworms feed by burying their anterior ends in the stained with Coomassie Brilliant Blue and immunoblots using intestinal mucosa of the host, rupturing capillaries and monoclonal antibodies to the vector-derived myc epitope. ingesting the liberated blood. Erythrocytes are lysed by pore Recombinant Ac-APR-1 was treated with PNGase F and O- formation [20], releasing hemoglobin (Hb) into the lumen of glycosidase, according to the manufacturer’s instructions the parasite’s intestine, where it is degraded by a semi- (Enzymatic CarboRelease kit; QA-Bio, San Mateo, California, ordered pathway of catalysis that involves aspartic, cysteine, United States), under denaturing conditions to remove any and metalloproteases [21]. Vaccination of dogs with a N-linked and O-linked oligosaccharides. Deglycosylation was catalytically active recombinant cysteine hemoglobinase, Ac- performed only to confirm the presence of N-linked sugars CP-2, induced antibodies that neutralized proteolytic activity on the recombinant molecule. All remaining studies were and provided partial protection to vaccinees by reducing egg conducted with the glycoprotein. output (a measure of intestinal worm burden) and worm size, but significant reductions of adult worm burdens and/or Activation and Hemoglobinolytic Activity of Recombinant blood loss
Load more

Recommended publications
  • Pichia Pastoris (Komagataella Phaffii) As a Cost-Effective Tool for Vaccine
    bioengineering Review Pichia pastoris (Komagataella phaffii) as a Cost-Effective Tool for Vaccine Production for Low- and Middle-Income Countries (LMICs) Salomé de Sá Magalhães and Eli Keshavarz-Moore * Department of Biochemical Engineering, University College London, Gower Street, London WC1E 6BT, UK; [email protected] * Correspondence: [email protected] Abstract: Vaccination is of paramount importance to global health. With the advent of the more recent pandemics, the urgency to expand the range has become even more evident. However, the potential limited availability and affordability of vaccines to resource low- and middle-income countries has created a need for solutions that will ensure cost-effective vaccine production methods for these countries. Pichia pastoris (P. pastoris) (also known as Komagataella phaffii) is one of the most promising candidates for expression of heterologous proteins in vaccines development. It combines the speed and ease of highly efficient prokaryotic platforms with some key capabilities of mammalian systems, potentially reducing manufacturing costs. This review will examine the latest developments in P. pastoris from cell engineering and design to industrial production systems with focus on vaccine development and with reference to specific key case studies. Keywords: vaccines; LMICs; expression platforms; P. pastoris (Komagataella phaffii) Citation: de Sá Magalhães, S.; Keshavarz-Moore, E. Pichia pastoris (Komagataella phaffii) as a Cost-Effective 1. Introduction Tool for Vaccine Production for Low- and Middle-Income Countries (LMICs). Infectious diseases have a significant global economic and societal impact. As a result, Bioengineering 2021, 8, 119. https:// during the last two centuries, we have witnessed the remarkable success of vaccination doi.org/10.3390/bioengineering8090119 reducing the burden of infectious diseases [1].
    [Show full text]
  • Artículos Científicos
    Editor: NOEL GONZÁLEZ GOTERA Número 086 Diseño: Lic. Roberto Chávez y Liuder Machado. Semana 010613 - 070613 Foto: Lic. Belkis Romeu e Instituto Finlay La Habana, Cuba. ARTÍCULOS CIENTÍFICOS Publicaciones incluidas en PubMED durante el período comprendido entre el el 1 y el 7 de junio de 2013. Con “vaccin*” en título: 131 artículos recuperados. Vacunas Neumococo (Streptococcus pneumoniae) 98. Is there an authentic increased risk of pneumococcal pneumonia among young mothers whose children were fully vaccinated with PCV7? The role of methodological shortcomings. Castiglia P, Piana A, Sotgiu G. Vaccine. 2013 May 29. doi:pii: S0264-410X(13)00655-5. 10.1016/j.vaccine.2013.05.055. [Epub ahead of print] No abstract available. PMID: 23727001 [PubMed - as supplied by publisher] Related citations Select item 23726847 121. Clonal Expansion within Pneumococcal Serotype 6C after Use of Seven-Valent Vaccine. Loman NJ, Gladstone RA, Constantinidou C, Tocheva AS, Jefferies JM, Faust SN, O'Connor L, Chan J, Pallen MJ, Clarke SC. PLoS One. 2013 May 28;8(5):e64731. doi: 10.1371/journal.pone.0064731. Print 2013. PMID: 23724086 [PubMed - in process] Free Article Related citations Select item 23724021 1 Vacuna Tosferina (Bordetella pertussis) 108. [Pertussis in fully vaccinated infants and children. Are new vaccination strategies required?] Moraga-Llop FA, Mendoza-Palomar N, Muntaner-Alonso A, Codina-Grau G, Fàbregas-Martori A, Campins-Martí M. Enferm Infecc Microbiol Clin. 2013 May 29. doi:pii: S0213-005X(13)00124-9. 10.1016/j.eimc.2013.04.007. [Epub ahead of print] Spanish. PMID: 23725786 [PubMed - as supplied by publisher] Related citations Select item 23725785 125.
    [Show full text]
  • The GAVI Alliance
    GLOBAL PROGRAM REVIEW The GAVI Alliance Global Program Review The World Bank’s Partnership with the GAVI Alliance Main Report and Annexes Contents ABBREVIATIONS .................................................................................................................................. V ACKNOWLEDGMENTS ........................................................................................................................ XI PROGRAM AT A GLANCE: THE GAVI ALLIANCE ............................................................................ XII KEY BANK STAFF RESPONSIBLE DURING PERIOD UNDER REVIEW ........................................ XIV GLOSSARY ......................................................................................................................................... XV OVERVIEW ........................................................................................................................................ XVII GAVI ALLIANCE MANAGEMENT RESPONSE .............................................................................. XXV WORLD BANK GROUP MANAGEMENT RESPONSE ................................................................... XXIX CHAIRPERSON’S SUMMARY ......................................................................................................... XXXI 1. THE WORLD BANK-GAVI PARTNERSHIP AND THE PURPOSE OF THE REVIEW ...................... 1 Evolution of GAVI .....................................................................................................................................................
    [Show full text]
  • Vaccines for the Twenty-First Century Society
    PERSPECTIVES expectancy is above 80 years and, bearing SCIENCE AND SOCIETY in mind that predictions of a ceiling to life expectancy have been repeatedly wrong, Vaccines for the twenty-first century we can extrapolate that it could reach 100 years in six decades2. A major reason society for the steady increase of life expectancy is greater control of infectious diseases — this has led to decreased early mortality Rino Rappuoli, Christian W. Mandl, Steven Black and Ennio De Gregorio (only one in four children used to reach the Abstract | Vaccines have been one of the major revolutions in the history of age of 20) and has also provided a longer lifespan in adults by decreasing their expo- mankind and, during the twentieth century, they eliminated most of the childhood sure to acute and chronic inflammatory diseases that used to cause millions of deaths. In the twenty-first century, vaccines processes1. will also play a major part in safeguarding people’s health. Supported by the Vaccination served extremely well the innovations derived from new technologies, vaccines will address the new needs needs of our twentieth-century society, of a twenty-first century society characterized by increased life expectancy, members of which had a life expectancy of approximately 55–65 years. By eliminating emerging infections and poverty in low-income countries. many infectious diseases that used to cause millions of deaths, vaccination contributed Health is probably the most important value average lifespan was 35 years in 1750 to the increase in our lifespan (FIG. 1). of our society, which enjoys an unprecedented (REF.
    [Show full text]
  • Immunization Bulletin, April 2007, Vol.XXIX, Number 2
    IMMUNIZE AND PROTECT YOUR FAMILY IN THIS ISSUE: PANAMERICANHEALTHORGANIZATION 1 AFP Surveillance in Canada 1 EPI Evaluation in Uruguay, 2006 6 Human Hookworm Vaccine Initiative 7 Update on Pro-Vac Initiative 8 Pan American Games & Rubella Alert Volume XXIX, Number 2 April 2007 Summary of EPI AFP Surveillance in Canada Evaluation in Uruguay, Elimination of indigenous wild poliovirus transmission was certified in Canada and the rest of the Region November 2006 of the Americas in September 1994. However, until global eradication of poliomyelitis is achieved, Canada recognizes there is an ongoing risk for importation of wild polioviruses.[1] Therefore, Canada maintains an The Pan American Health Organiza- acute flaccid paralysis (AFP) surveillance system with the overall goal to ensure prompt investigation of AFP tion (PAHO) offers its Member States cases to rule out poliovirus infections, in keeping with recommendations from the World Health Organiza- the opportunity to evaluate their tion (WHO).[2] This article describes the results of AFP surveillance for 2006 in Canada and highlights chal- national immunization programs lenges. through an international multidisci- plinary evaluation of the Expanded Methods Program on Immunization (EPI). The EPI evaluation serves as a tool for Canada’s AFP case definition includes any patient aged <15 years with onset of focal weakness or paralysis monitoring program advances and characterized as flaccid (reduced tone) without other obvious cause (e.g., trauma). Key surveillance indica- assessing the degree of development tors are based on WHO quality assurance criteria. They are as follows: and technical capacity available to 1) Sensitivity of surveillance: The ability to detect at least one case of non-polio AFP (including Guillain-Barré face new challenges.
    [Show full text]
  • English Questionnaire
    Standard Template for a Candidate Demonstration Project Note: the questions with asterisk should be filled. 1.* Title of the project: Improving health quality and wellbeing of the economically marginalized populations in Southeast Asia: An initiative towards the introduction of a human hookworm vaccine (IIHHVac) 2.* Submitted by: 3.* Target disease or health condition: (Focus on type II and III diseases and special RandD needs of developing countries in type I diseases where there is an identified health technology gap.) Hookworm disease 4.* The suggested health technology that project seeks to develop: (e.g. medicine; diagnostic test; medical device; vaccine etc.) Hookworm vaccine 5.* Project summary: (Maximum 500 words) Hookworm disease is the leading cause of iron deficiency anemia in the world’s poorest regions [1]. It is a major socioeconomic and public health concern. It is estimated that 600 million people are chronically infected, with up to135,000 deaths annually [2]. Most infections occur in the Asian region (60-70million people in each), followed by Nigeria and the Democratic Republic of Congo in Africa and Brazil (30-40 million people in each) [3]. The economic burden of chronic hookworm infection is estimated at 4.5 million DALYs annually [4] and is among the most important neglected tropical disease [5]. Southeast Asia (SEA) has a large percentage of populations living in rural and remote areas where hookworm infection is common [6]. These areas generally have poor sanitation and access to untreated water, which increase the opportunity of hookworm transmission and infection. Hookworm infection has been associated with impaired learning and decrease in productivity [7].
    [Show full text]
  • 2012 NIAID Jordan Report
    THE JORDAN REPORT ACCELERATED DEVELOPMENT OF VACCINES 2012 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Allergy and Infectious Diseases Images on cover, from the top: Courtesy of the US Centers for Disease Control and Prevention; istock.com; Courtesy of the National Library of Medicine; Courtesy of MedImmune THE JORDAN REPORT ACCELERATED DEVELOPMENT OF VACCINES 2012 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Allergy and Infectious Diseases NIH Publication No. 11-7778 January 2012 www.niaid.nih.gov ADDITIONAL RESOURCES National Institute of Allergy and Infectious Diseases, www.niaid.nih.gov Vaccines.gov: your best shot at good health, www.vaccines.gov Centers for Disease Control and Prevention: Immunization Schedules, www.cdc.gov/vaccines/recs/schedules/ Table of Contents INTRODUCTION VACCINE UPDATES Foreword by Anthony S. Fauci, M.D. ......................................... 3 Dengue M. Cristina Cassetti, Ph.D. .......................................................... 95 Tribute by Carole A. Heilman, Ph.D. ......................................... 5 HIGHLIGHT BOX Vaccine Against Chikungunya Virus in Development EXPERT ARTICLES Gary J. Nabel, M.D., Ph.D. and Ken Pekoc ......................... 97 Vaccinomics and Personalized Vaccinology Severe Acute Respiratory Syndrome Gregory A. Poland, M.D., Inna G. Ovsyannikova, Ph.D. and Frederick J. Cassels, Ph.D. ............................................................ 98 Robert M. Jacobson, M.D. .............................................................11 HIGHLIGHT BOX Sex Differences in Immune Responses to Vaccines Vaccine Delivery Technologies Col. Renata J. M. Engler, M.D. and Mary M. Klote, M.D. ....... 19 Martin H. Crumrine, Ph.D. ................................................. 105 Immunization and Pregnancy West Nile Virus Flor M. Munoz, M.D. .................................................................. 27 Patricia M. Repik, Ph.D.
    [Show full text]
  • Investigating the Community-Level Variation in Hookworm Prevalence in the Kpandai District, Ghana: a Mixed-Methods Study
    Yale University EliScholar – A Digital Platform for Scholarly Publishing at Yale Public Health Theses School of Public Health January 2020 Investigating The Community-Level Variation In Hookworm Prevalence In The Kpandai District, Ghana: A Mixed-Methods Study Harry Hyunteh Hyunteh Kim [email protected] Follow this and additional works at: https://elischolar.library.yale.edu/ysphtdl Recommended Citation Kim, Harry Hyunteh Hyunteh, "Investigating The Community-Level Variation In Hookworm Prevalence In The Kpandai District, Ghana: A Mixed-Methods Study" (2020). Public Health Theses. 1960. https://elischolar.library.yale.edu/ysphtdl/1960 This Open Access Thesis is brought to you for free and open access by the School of Public Health at EliScholar – A Digital Platform for Scholarly Publishing at Yale. It has been accepted for inclusion in Public Health Theses by an authorized administrator of EliScholar – A Digital Platform for Scholarly Publishing at Yale. For more information, please contact [email protected]. INVESTIGATING THE COMMUNITY-LEVEL VARIATION IN HOOKWORM PREVALENCE IN THE KPANDAI DISTRICT, GHANA: A MIXED-METHODS STUDY A Thesis Submitted to the Department of Epidemiology of Microbial Diseases Yale University School of Public Health in Partial Fulfillment of the Requirements for the Degree of Master of Public Health May 2020 by Harry Hyunteh Kim May 2020 Kim 1 Abstract Soil-transmitted helminths are a major cause of disability and morbidity in resource- poor settings: over 1.5 billion are estimated to be at risk of infection. Human behaviors and household socioeconomic conditions that facilitate contact with contaminated soil may increase exposure to parasites. The primary objective of the study was to investigate the community-level variation in hookworm prevalence in the Kpandai district of Ghana.
    [Show full text]
  • Developing Vaccines to Combat Hookworm Infection and Intestinal Schistosomiasis
    REVIEWS Developing vaccines to combat hookworm infection and intestinal schistosomiasis Peter J. Hotez*, Jeffrey M. Bethony*‡, David J. Diemert*‡, Mark Pearson§ and Alex Loukas§ Abstract | Hookworm infection and schistosomiasis rank among the most important health problems in developing countries. Both cause anaemia and malnutrition, and schistosomiasis also results in substantial intestinal, liver and genitourinary pathology. In sub-Saharan Africa and Brazil, co-infections with the hookworm, Necator americanus, and the intestinal schistosome, Schistosoma mansoni, are common. The development of vaccines for these infections could substantially reduce the global disability associated with these helminthiases. New genomic, proteomic, immunological and X-ray crystallographic data have led to the discovery of several promising candidate vaccine antigens. Here, we describe recent progress in this field and the rationale for vaccine development. In terms of their global health impact on children and that combat hookworm and schistosomiasis, with an pregnant women, as well as on adults engaged in subsist- emphasis on disease caused by Necator americanus, the ence farming, human hookworm infection (known as major hookworm of humans, and Schistosoma mansoni, ‘hookworm’) and schistosomiasis are two of the most the primary cause of intestinal schistosomiasis. common and important human infections1,2. Together, their disease burdens exceed those of all other neglected Global distribution and pathobiology tropical diseases3–6. They also trap the world’s poorest Hookworms are roundworm parasites that belong to people in poverty because of their deleterious effects the phylum Nematoda. They share phylogenetic simi- on child development and economic productivity7–9. larities with the free-living nematode Caenorhabditis Until recently, the importance of these conditions as elegans and with the parasitic nematodes Nippostrongylus global health and economic problems had been under- brasiliensis and Heligmosomoides polygyrus, which are appreciated.
    [Show full text]
  • Schistosomiasis Vaccine Development: Update on Human Clinical Trials Adebayo J
    Molehin Journal of Biomedical Science (2020) 27:28 https://doi.org/10.1186/s12929-020-0621-y REVIEW Open Access Schistosomiasis vaccine development: update on human clinical trials Adebayo J. Molehin1,2 Abstract Schistosomiasis causes significant levels of morbidity and mortality in many geographical regions of the world. The disease is caused by infections with parasitic blood flukes known as schistosomes. The control of schistosomiasis over the last several decades has been centered on the mass drug administration (MDA) of praziquantel (PZQ), which is the only drug currently available for treatment. Despite the concerted efforts of MDA programs, the prevalence and transmission of schistosomiasis has remained largely unchecked due to the fact that PZQ is ineffective against juvenile schistosomes, does not prevent re-infection and the emergence of PZQ-resistant parasites. In addition, other measures such as the water, sanitation and hygiene programs and snail intermediate hosts control have had little to no impact. These drawbacks indicate that the current control strategies are severely inadequate at interrupting transmission and therefore, implementation of other control strategies are required. Ideally, an efficient vaccine is what is needed for long term protection thereby eliminating the current efforts of repeated mass drug administration. However, the general consensus in the field is that the integration of a viable vaccine with MDA and other control measures offer the best chance of achieving the goal of schistosomiasis elimination.
    [Show full text]
  • Preparation of a Community for Clinical Trials of a Vaccine Against Hookworm in an Endemic Area of Brazil
    Health Education through Analogies: Preparation of a Community for Clinical Trials of a Vaccine against Hookworm in an Endemic Area of Brazil Maria Flavia Gazzinelli1, Lucas Lobato1, Leonardo Matoso1, Renato Avila1, Rita de Cassia Marques1, Ami Shah Brown2, Rodrigo Correa-Oliveira3, Jeffrey M. Bethony4, David J. Diemert2,4* 1 School of Nursing, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil, 2 Albert B. Sabin Vaccine Institute, Washington, District of Columbia, United States of America, 3 Centro de Pesquisas Rene´ Rachou, Belo Horizonte, Minas Gerais, Brazil, 4 Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, District of Columbia, United States of America Abstract Background: Obtaining informed consent for clinical trials is especially challenging when working in rural, resource-limited areas, where there are often high levels of illiteracy and lack of experience with clinical research. Such an area, a remote field site in the northeastern part of the state of Minas Gerais, Brazil, is currently being prepared for clinical trials of experimental hookworm vaccines. This study was conducted to assess whether special educational tools can be developed to increase the knowledge and comprehension of potential clinical trial participants and thereby enable them to make truly informed decisions to participate in such research. Methodology/Principal Findings: An informational video was produced to explain the work of the research team and the first planned hookworm vaccine trial, using a pedagogical method based on analogies. Seventy-two adults living in a rural community of Minas Gerais were administered a structured questionnaire that assessed their knowledge of hookworm, of research and of the planned hookworm vaccine trial, as well as their attitudes and perceptions about the researchers and participation in future vaccine trials.
    [Show full text]
  • Sabin Vaccine Report
    Volume VIII, Number 1 Sabin Vaccine Spring 2005 EPORT The newsletter of the Albert B. Sabin Vaccine InstituteR — dedicated to disease prevention www.sabin.org FDA Clears Human Hookworm Vaccine for Phase I Safety Trials Sabin/GW Researchers Receive Word on Investigational New Drug Status for Vaccine Clinical trials to test the safety of a gin safety trials is a major milestone for in individuals who suffer from hook- first-of-its-kind human hookworm vac- the human hookworm vaccine project,” worm infection.” cine will begin in the Washington, DC Hotez said. “It has taken an amazing Human hookworm infection is caused area in the coming weeks after the U.S. amount of our team’s effort to get us to by parasitic worms that fasten onto the Food and Drug Administration conferred the current stage of vaccine develop- inner layers of the small intestine using investigational new drug status on the ment. Of course, our ultimate goal is to their teeth-like projections and cause vaccine this past January. No current take this research to developing coun- blood loss at the attachment site. vaccine is available to prevent hook- tries where the vaccine will be tested Hookworm disease refers to the iron worm disease, which is one of the most Continued on page 4 common chronic infections of humans with an estimated 740 million cases in The village of Americaninhas, areas of rural poverty in the tropics in a rural part of Minas Gerais and subtropics. state in Brazil, is the focus of a The Human Hookworm Vaccine Ini- field study of hookworm dis- tiative (HHVI) is sponsored by the ease burden, being conducted Albert B.
    [Show full text]