An experimental vaccine for hepatitis e adjuvantated with saponins derived from leaves from the soap tree Quillaja brasiliensis

MÜLLER, MELISA; WALLACE, F; SACUR, JACINTO; VERA, DANIELA; BRANCHER, M; RAFAELA, J; JULIO VILLENA; KITAZAWA, HARUKI; FERREIRA, F ; OLIVARO, C; VIZOSO-PINTO, GUADALUPE

London

Simposio; 2nd International Hepatitis E Symposium; 2023

International Hepatitis E Society

Hepatitis E is increasingly reported in industrialized countries mainly associated to zoonotic transmission via consumption of meat products derived from contaminated animals. Hepatitis E virus genotype 3 (HEV-3) is the main genotype associated with this transmission. Although swine, the main reservoir, do not suffer from the disease, a veterinary vaccine could help controlling the disease before it reaches human beings. QuilA® is a potent adjuvant used in veterinary vaccines and consists of a mixture of saponins obtained from the barks of the Chilean tree Quillaja saponaria. The high demand for the pharmaceutical and cosmetic industries and the tree destructive source have posed the trees at risk. We have recently obtained saponins extracts from the leaves and bark of Quillaja brasilensis (an endemic tree from Argentina, Uruguay, Brazil, and Paraguay) and isolated a novel molecule, Qb1, with adjuvant potential. The aim of this study was to evaluate an experimental vaccine consisting of the recombinant protein HEV-3 ORF2 mixed with the extracts and purified saponins of Quillaja brasiliensis. The leaves of Quillaja brasiliensis represent a renewable and friendly source of fraction B (a complex mixture of saponins with similarities and differences with the commercial QuilA®). Qb1, the novel isolated molecule, isomer of the commercial QS21®, has good adjuvant properties and a distinct mechanism. Using these adjuvants and the recombinant HEV-3 ORF2, we have developed an experimental vaccine that induces high titers of specific IgG even after the first immunization. The stimulation of macrophages reveals a unique mechanism of action in which both proinflammatory and regulatory cytokines are produced and were regulators are also activated in a singular manner. This promising formulation should be further investigated to develop a veterinary vaccine for HEV. Further, the novel Qb molecule and fraction B may be combined with other antigens for novel vaccine formulations against other pathogens.