IMXQB-80: A Quillaja brasiliensis saponin-based nanoadjuvant enhances Zika virus specific immune responses in mice |
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Authors: | Samuel Cibulski Thais Fumaco Teixeira Ana Paula Muterle Varela Matheus Fabião de Lima Gabriela Casanova Yuri Mangueira Nascimento Josean Fechine Tavares Marcelo Sobral da Silva Patrícia Sesterheim Diogo Onofre Souza Paulo Michel Roehe Fernando Silveira |
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Institution: | 1. Centro de Biotecnologia – CBiotec, Laboratório de Biotecnologia Celular e Molecular, Universidade Federal da Paraíba, João Pessoa, Paraíba, Brazil;2. Departamento de Microbiologia Imunologia e Parasitologia, Laboratório de Virologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil;3. Unidad de Microscopía Electrónica de Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay;4. Institute for Research in Pharmaceutical and Medications, Universidade Federal da Paraíba, João Pessoa, Paraíba, Brazil;5. Centro de Cardiologia Experimental, Instituto de Cardiologia/Fundação Universitária de Cardiologia, Porto Alegre, RS, Brazil;6. Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil;7. Departamento de Desarrollo Biotecnológico, Instituto de Higiene, Facultad de Medicina, Universidad de la República (UdelaR), Montevideo, Uruguay |
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Abstract: | Vaccine adjuvants are compounds that enhance/prolong the immune response to a co-administered antigen. Saponins have been widely used as adjuvants for many years in several vaccines – especially for intracellular pathogens – including the recent and somewhat revolutionary malaria and shingles vaccines. In view of the immunoadjuvant potential of Q. brasiliensis saponins, the present study aimed to characterize the QB-80 saponin-rich fraction and a nanoadjuvant prepared with QB-80 and lipids (IMXQB-80). In addition, the performance of such adjuvants was examined in experimental inactivated vaccines against Zika virus (ZIKV). Analysis of QB-80 by DI-ESI-ToF by negative ion electrospray revealed over 29 saponins that could be assigned to known structures existing in their congener Q. saponaria, including the well-studied QS-21 and QS-7. The QB-80 saponins were a micrOTOF able to self-assembly with lipids in ISCOM-like nanoparticles with diameters of approximately 43 nm, here named IMXQB-80. Toxicity assays revealed that QB-80 saponins did present some haemolytical and cytotoxic potentials; however, these were abrogated in IMXQB-80 nanoparticles. Regarding the adjuvant activity, QB-80 and IMXQB-80 significantly enhanced serum levels of anti-Zika virus IgG and subtypes (IgG1, IgG2b, IgG2c) as well as neutralized antibodies when compared to an unadjuvanted vaccine. Furthermore, the nanoadjuvant IMXQB-80 was as effective as QB-80 in stimulating immune responses, yet requiring fourfold less saponins to induce the equivalent stimuli, and with less toxicity. These findings reveal that the saponin fraction QB-80, and particularly the IMXQB-80 nanoadjuvant, are safe and capable of potentializing immune responses when used as adjuvants in experimental ZIKV vaccines. |
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Keywords: | Zika virus Saponins Nanoadjuvant Immune system Vaccine |
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