IMXQB-80: A Quillaja brasiliensis saponin-based nanoadjuvant enhances Zika virus specific immune responses in mice. Issue 3 (15th January 2021)

• Record Type: Journal Article
• Authors: Cibulski, Samuel; Teixeira, Thais Fumaco; Varela, Ana Paula Muterle; de Lima, Matheus Fabião; Casanova, Gabriela; Nascimento, Yuri Mangueira; Fechine Tavares, Josean; da Silva, Marcelo Sobral; Sesterheim, Patrícia; Souza, Diogo Onofre; Roehe, Paulo Michel; Silveira, Fernando
• Is Part Of: Vaccine. Volume 39:Issue 3(2021)
• Page Start: 571
• Page End: 579
• Publication Date: 2021-01-15
• Subjects: Zika virus -- Saponins -- Quillaja brasiliensis -- Nanoadjuvant -- Immune system -- Vaccine; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2020.12.004
• Languages: English
• ISSNs: 0264-410X

Abstract

Graphical abstract: Highlights: Q. brasiliensis QB-80 saponins revealed chemical similarities to the commercial Q. saponaria barks-extracted saponin. The QB-80 saponins were able to self-assembly with lipids in ISCOM-like nanoparticle named IMXQB-80. Subcutaneous administration of QB-80 and IMXQB-80 induced high titres of anti-Zika virus with neutralizing antibodies. 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.