A randomized, controlled Phase 1b trial of the Sm-TSP-2 Vaccine for intestinal schistosomiasis in healthy Brazilian adults living in an endemic area.

Autor: Diemert DJ; Department of Medicine, School of Medicine and Health Sciences, The George Washington University, Washington DC, United States of America.; Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington DC, United States of America., Correa-Oliveira R; Instituto René Rachou, Fundação Oswaldo Cruz em Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Fraga CG; Instituto René Rachou, Fundação Oswaldo Cruz em Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Talles F; Instituto René Rachou, Fundação Oswaldo Cruz em Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Silva MR; Instituto René Rachou, Fundação Oswaldo Cruz em Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Patel SM; Departments of Molecular Virology & Microbiology and Medicine, Baylor College of Medicine, Houston, Texas, United States of America., Galbiati S; The Emmes Company, LLC, Frederick, Maryland, United States of America., Kennedy JK; The Emmes Company, LLC, Frederick, Maryland, United States of America., Lundeen JS; The Emmes Company, LLC, Frederick, Maryland, United States of America., Gazzinelli MF; Instituto René Rachou, Fundação Oswaldo Cruz em Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Li G; Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington DC, United States of America., Hoeweler L; Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington DC, United States of America., Deye GA; Division of Microbiology and Infectious Diseases (DMID), National Institutes of Allergy and Infectious, Diseases (NIAID), National Institutes of Health (NIH), United States of America., Bottazzi ME; Texas Children's Hospital Center for Vaccine Development, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States of America., Hotez PJ; Texas Children's Hospital Center for Vaccine Development, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States of America., El Sahly HM; Departments of Molecular Virology & Microbiology and Medicine, Baylor College of Medicine, Houston, Texas, United States of America., Keitel WA; Departments of Molecular Virology & Microbiology and Medicine, Baylor College of Medicine, Houston, Texas, United States of America., Bethony J; Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University, Washington DC, United States of America., Atmar RL; Departments of Molecular Virology & Microbiology and Medicine, Baylor College of Medicine, Houston, Texas, United States of America.
Jazyk: angličtina
Zdroj: PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2023 Mar 30; Vol. 17 (3), pp. e0011236. Date of Electronic Publication: 2023 Mar 30 (Print Publication: 2023).
DOI: 10.1371/journal.pntd.0011236
Abstrakt: Background: Recombinant Schistosoma mansoni Tetraspanin-2 formulated on Alhydrogel (Sm-TSP-2/Alhydrogel) is being developed to prevent intestinal and hepatic disease caused by S. mansoni. The tegumentary Sm-TSP-2 antigen was selected based on its unique recognition by cytophilic antibodies in putatively immune individuals living in areas of ongoing S. mansoni transmission in Brazil, and preclinical studies in which vaccination with Sm-TSP-2 protected mice following infection challenge.
Methods: A randomized, observer-blind, controlled, Phase 1b clinical trial was conducted in 60 healthy adults living in a region of Brazil with ongoing S. mansoni transmission. In each cohort of 20 participants, 16 were randomized to receive one of two formulations of Sm-TSP-2 vaccine (adjuvanted with Alhydrogel only, or with Alhydrogel plus the Toll-like receptor-4 agonist, AP 10-701), and 4 to receive Euvax B hepatitis B vaccine. Successively higher doses of antigen (10 μg, 30 μg, and 100 μg) were administered in a dose-escalation fashion, with progression to the next dose cohort being dependent upon evaluation of 7-day safety data after all participants in the preceding cohort had received their first dose of vaccine. Each participant received 3 intramuscular injections of study product at intervals of 2 months and was followed for 12 months after the third vaccination. IgG and IgG subclass antibody responses to Sm-TSP-2 were measured by qualified indirect ELISAs at pre- and post-vaccination time points through the final study visit.
Results: Sm-TSP-2/Alhydrogel administered with or without AP 10-701 was well-tolerated in this population. The most common solicited adverse events were mild injection site tenderness and pain, and mild headache. No vaccine-related serious adverse events or adverse events of special interest were observed. Groups administered Sm-TSP-2/Alhydrogel with AP 10-701 had higher post-vaccination levels of antigen-specific IgG antibody. A significant dose-response relationship was seen in those administered Sm-TSP-2/Alhydrogel with AP 10-701. Peak anti-Sm-TSP-2 IgG levels were observed approximately 2 weeks following the third dose, regardless of Sm-TSP-2 formulation. IgG levels fell to low levels by Day 478 in all groups except the 100 μg with AP 10-701 group, in which 57% of subjects (4 of 7) still had IgG levels that were ≥4-fold higher than baseline. IgG subclass levels mirrored those of total IgG, with IgG1 being the predominant subclass response.
Conclusions: Vaccination of adults with Sm-TSP-2/Alhydrogel in an area of ongoing S. mansoni transmission was safe, minimally reactogenic, and elicited significant IgG and IgG subclass responses against the vaccine antigen. These promising results have led to initiation of a Phase 2 clinical trial of this vaccine in an endemic region of Uganda.
Trial Registration: NCT03110757.
Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: PH, MEB, DJD and JB are patent holders for a multivalent anthelminthic vaccine including schistosomiasis. GAD is an employee of the Sponsor, NIAID. RLA, RC-O, CGF, FT, MR, SG, JKK, JSL, MFG, GL, LH, WAK, SP, HMES: None.
(Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)
Databáze: MEDLINE
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