Journal Article

IMXQB-80: A Quillaja brasiliensis saponin-based nanoadjuvant enhances Zika virus specific immune responses in mice

Nascimento, Yuri Mangueira, Cibulski, Samuel, Roehe, Paulo Michel, de Lima, Matheus Fabião, Fechine Tavares, Josean, Silveira, Fernando, Teixeira, Thais Fumaco, Sesterheim, Patrícia, Varela, Ana Paula Muterle, Souza, Diogo Onofre, Casanova, Gabriela, da Silva, Marcelo Sobral

2021

Overview

[Display omitted] •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. 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.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Adjuvants / Adjuvants, Immunologic / Allergy and Immunology / Animals / Antibodies / Antigens / blood serum / Congeners / Cytotoxicity / Guillain-Barre syndrome / Herpes zoster / Immune response / Immune system / Immunity / Immunoglobulin G / ISCOMS / Lipids / Malaria / Mice / Nanoadjuvant / Nanoparticles / Negative ions / neutralization / Pathogens / Quillaja / Quillaja brasiliensis / Quillaja Saponins / Saponins / Seawater / Self-assembly / Serum levels / Toxicity / Vaccine / Vaccines / Vector-borne diseases / Viral infections / Viruses / Zika Virus / Zika Virus Infection - prevention & control