Non-clinical toxicity and immunogenicity evaluation of a Plasmodium vivax malaria vaccine using Poly-ICLC (Hiltonol®) as adjuvant.

Autor: Marques RF; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, São Paulo, SP, Brazil., Gimenez AM; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, São Paulo, SP, Brazil., Caballero O; Orygen Biotecnologia, São Paulo, SP, Brazil., Simpson A; Orygen Biotecnologia, São Paulo, SP, Brazil., Salazar AM; Oncovir, Inc. Washington, Washington, DC, United States of America., Amino R; Department of Parasites and Insect Vectors, Pasteur Institute, Paris, France., Godin S; Smithers Avanza Toxicology Services, Gaithersburg, MD, United States of America., Gazzinelli RT; Centro de Tecnologia em Vacinas, Universidade Federal de Minas Gerais, Parque Tecnológico de Belo Horizonte, Belo Horizonte, MG, Brazil., Soares IS; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, São Paulo, SP, Brazil. Electronic address: isoares@usp.br.
Jazyk: angličtina
Zdroj: Vaccine [Vaccine] 2024 Apr 02; Vol. 42 (9), pp. 2394-2406. Date of Electronic Publication: 2024 Mar 06.
DOI: 10.1016/j.vaccine.2024.02.070
Abstrakt: Malaria caused byPlasmodium vivaxis a pressing public health problem in tropical and subtropical areas.However, little progress has been made toward developing a P. vivaxvaccine, with only three candidates being tested in clinical studies. We previously reported that one chimeric recombinant protein (PvCSP-All epitopes) containing the conserved C-terminus of the P. vivax Circumsporozoite Protein (PvCSP), the three variant repeat domains, and aToll-like receptor-3 agonist,Poly(I:C), as an adjuvant (polyinosinic-polycytidylic acid, a dsRNA analog mimicking viral RNA), elicits strong antibody-mediated immune responses in mice to each of the three allelic forms of PvCSP. In the present study, a pre-clinical safety evaluation was performed to identify potential local and systemic toxic effects of the PvCSP-All epitopes combined with the Poly-ICLC (Poly I:C plus poly-L-lysine, Hiltonol®) or Poly-ICLC when subcutaneously injected into C57BL/6 mice and New Zealand White Rabbits followed by a 21-day recovery period. Overall, all observations were considered non-adverse and were consistent with the expected inflammatory response and immune stimulation following vaccine administration. High levels of vaccine-induced specific antibodies were detected both in mice and rabbits. Furthermore, mice that received the vaccine formulation were protected after the challenge with Plasmodium berghei sporozoites expressing CSP repeats from P. vivax sporozoites (Pb/Pv-VK210). In conclusion, in these non-clinical models, repeated dose administrations of the PvCSP-All epitopes vaccine adjuvanted with a Poly-ICLC were immunogenic, safe, and well tolerated.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: R.F.M., A.M.G., and I.S.S. are co-inventors of the potential P. vivax vaccine evaluated in this study. The patent is under evaluation process, application number BR102022005915-2. A.M.S is President and CEO of Oncovir, Inc., which is developing poly-ICLC (Hiltonol) for clinical trials. O.C. and A.S work for Orygen® which licensed Hiltonol from Oncovir for Latin America.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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