Marilia Santini-Oliveira1, Rhea N Coler2, Juçara Parra3, Valdilea Veloso1, Lakshmi Jayashankar2, Patricia M Pinto4, Marcia A Ciol5, Robert Bergquist6, Steven G Reed2, Miriam Tendler7. 1. Instituto Nacional de Infectologia Evandro Chagas (INI), Fiocruz, Av. Brasil, No. 4365, Manguinhos, Rio de Janeiro, 21045-900, Brazil. 2. Infectious Disease Research Institute (IDRI), 1616, Eastlake Ave E, Suite 400, Seattle, WA 98102, USA. 3. Fiocruz/MS, Rua Gabriel Abrão s/n, Jardim das Nações, Campo Grande, Mato Grosso do Sul, 79.081-746, Brazil. 4. Laboratório de Esquistossomose Experimental, Instituto Oswaldo Cruz, Fiocruz, Av. Brasil, No. 4365, Manguinhos, 21045-900 Rio de Janeiro, Brazil. 5. Department of Rehabilitation Medicine, School of Medicine, University of Washington, 1959 NE Pacific St, UW Box 356490, Seattle, WA 98195-6490, USA. 6. Geospatial Health, Ingerod 407, S-45494 Brastad, Sweden. 7. Laboratório de Esquistossomose Experimental, Instituto Oswaldo Cruz, Fiocruz, Av. Brasil, No. 4365, Manguinhos, 21045-900 Rio de Janeiro, Brazil. Electronic address: mtendler@ioc.fiocruz.br.
Abstract
DESIGN: Safety and immunogenicity of a recombinant 14kDa, fatty acid-binding protein(FABP) from Schistosoma mansoni (rSm14) were evaluated through an open, non-placebo-controlled, dose-standardized trial, performed at a single research site. The vaccine was formulated with glucopyranosyl lipid A (GLA) adjuvant in an oil-in-water emulsion (SE) and investigated in 20 male volunteers from a non-endemic area for schistosomiasis in the state of Rio de Janeiro, Brazil. Fifty microgram rSm14 with 10 μg GLA-SE (rSm14/GLA-SE)/dose were given intramuscularly three times with 30-day intervals. Participants were assessed clinically, biochemically and immunologically for up to 120 days. METHODS: Participants were screened for inclusion by physical examination, haematology and blood chemistry; then followed to assess adverse events and immunogenicity. Sera were tested for IgG (total and isotypes) and IgE. T cell induction of cytokines IL-2, IL-5, IL-10, IFNγ and TNFα was assessed by Milliplex kit and flow cytometry. RESULTS: The investigational product showed high tolerability; some self-limited, mild adverse events were observed during and after vaccine administration. Significant increases in Sm14-specific total IgG, IgG1 and IgG3 were observed 30 days after the first vaccination with specific IgG2 and IgG4 after 60 days. An increase in IgE antibodies was not observed at any time point. The IgG response was augmented after the second dose and 88% of all vaccinated subjects had developed high anti-Sm14 IgG titres 90 days after the first injection. From day 60 and onwards, there was an increase in CD4(+) T cells producing single cytokines, particularly TNFα and IL-2, with no significant increase of multi-functional TH1 cells. CONCLUSION: Clinical trial data on tolerability and specific immune responses after vaccination of adult, male volunteers in a non-endemic area for schistosomiasis with rSm14/GLA-SE, support this product as a safe, strongly immunogenic vaccine against schistosomiasis paving the way for follow-up Phase 2 trials. Study registration ID: NCT01154049 at http://www.clinicaltrials.gov.
DESIGN: Safety and immunogenicity of a recombinant 14kDa, fatty acid-binding protein(FABP) from Schistosoma mansoni (rSm14) were evaluated through an open, non-placebo-controlled, dose-standardized trial, performed at a single research site. The vaccine was formulated with glucopyranosyl lipid A (GLA) adjuvant in an oil-in-water emulsion (SE) and investigated in 20 male volunteers from a non-endemic area for schistosomiasis in the state of Rio de Janeiro, Brazil. Fifty microgram rSm14 with 10 μg GLA-SE (rSm14/GLA-SE)/dose were given intramuscularly three times with 30-day intervals. Participants were assessed clinically, biochemically and immunologically for up to 120 days. METHODS:Participants were screened for inclusion by physical examination, haematology and blood chemistry; then followed to assess adverse events and immunogenicity. Sera were tested for IgG (total and isotypes) and IgE. T cell induction of cytokines IL-2, IL-5, IL-10, IFNγ and TNFα was assessed by Milliplex kit and flow cytometry. RESULTS: The investigational product showed high tolerability; some self-limited, mild adverse events were observed during and after vaccine administration. Significant increases in Sm14-specific total IgG, IgG1 and IgG3 were observed 30 days after the first vaccination with specific IgG2 and IgG4 after 60 days. An increase in IgE antibodies was not observed at any time point. The IgG response was augmented after the second dose and 88% of all vaccinated subjects had developed high anti-Sm14 IgG titres 90 days after the first injection. From day 60 and onwards, there was an increase in CD4(+) T cells producing single cytokines, particularly TNFα and IL-2, with no significant increase of multi-functional TH1 cells. CONCLUSION: Clinical trial data on tolerability and specific immune responses after vaccination of adult, male volunteers in a non-endemic area for schistosomiasis with rSm14/GLA-SE, support this product as a safe, strongly immunogenic vaccine against schistosomiasis paving the way for follow-up Phase 2 trials. Study registration ID: NCT01154049 at http://www.clinicaltrials.gov.
Authors: Weidong Zhang; Adebayo J Molehin; Juan U Rojo; Justin Sudduth; Pramodh K Ganapathy; Eunjee Kim; Arif J Siddiqui; Jasmin Freeborn; Souad R Sennoune; Jordan May; Samra Lazarus; Catherine Nguyen; Whitni K Redman; Gul Ahmad; Workineh Torben; Souvik Karmakar; Loc Le; Kameswara R Kottapalli; Pratibha Kottapalli; Roman F Wolf; James F Papin; David Carey; Sean A Gray; Jenn D Bergthold; Raymond T Damian; Bryan T Mayer; Florian Marks; Steven G Reed; Darrick Carter; Afzal A Siddiqui Journal: Ann N Y Acad Sci Date: 2018-08 Impact factor: 5.691
Authors: Marie-Astrid Hoogerwerf; Jan Pieter R Koopman; Marijke C C Langenberg; Jacqueline J Janse; Janneke Kos-van Oosterhoud; Carola Feijt; Simon P Jochems; Claudia J de Dood; Roos van Schuijlenburg; Arifa Ozir-Fazalalikhan; Mikhael D Manurung; Erliyani Sartono; Martha T van der Beek; Béatrice M F Winkel; Petra H Verbeek-Menken; Koen A Stam; Fijs W B van Leeuwen; Pauline Meij; Angela van Diepen; Lisette van Lieshout; Govert J van Dam; Paul L A M Corstjens; Cornelis H Hokke; Maria Yazdanbakhsh; Leo G Visser; Meta Roestenberg Journal: Nat Med Date: 2020-02-17 Impact factor: 53.440
Authors: Adebayo J Molehin; Juan U Rojo; Sabrina Z Siddiqui; Sean A Gray; Darrick Carter; Afzal A Siddiqui Journal: Expert Rev Vaccines Date: 2016-01-13 Impact factor: 5.217
Authors: Emilie Seydoux; Hong Liang; Natasha Dubois Cauwelaert; Michelle Archer; Nicholas D Rintala; Ryan Kramer; Darrick Carter; Christopher B Fox; Mark T Orr Journal: J Immunol Date: 2018-05-16 Impact factor: 5.422
Authors: Kelsey A Gregg; Erin Harberts; Francesca M Gardner; Mark R Pelletier; Corinne Cayatte; Li Yu; Michael P McCarthy; Jason D Marshall; Robert K Ernst Journal: Vaccine Date: 2018-05-31 Impact factor: 3.641
Authors: Steven G Reed; Darrick Carter; Corey Casper; Malcolm S Duthie; Christopher B Fox Journal: Semin Immunol Date: 2018-10-23 Impact factor: 11.130