Author:
Bonduelle Olivia,Chaudesaigues Chloé,Tolazzi Monica,Suleiman Ehsan,de Bernard Simon,Alves Karine,Nourikyan Julien,Bohec Mylene,Baudrin Laura G.,Katinger Dietmar,Debré Patrice,Scarlatti Gabriella,Vieillard Vincent,Combadière Behazine
Abstract
W614A-3S peptide is a modified 3S motif of the HIV-gp41 (mutation W614A). We previously detected the presence of natural neutralizing antibodies directed against W614A-3S peptide (NAbs) in long-term non-progressor HIV+patients. Here, we compared the efficacy of W614A-3S peptide formulated in either squalene emulsion (SQE) or in aluminum hydroxide (Alum) in inducing broadly-NAbs (bNAbs). Rabbit and mouse models were used to screen the induction of bNAbs following 4 immunizations. SQE was more efficient than Alum formulation in inducing W614A-3S-specific bNAbs with up to 67%–93% of HIV strains neutralized. We then analyzed the quality of peptide-specific murine B cells by single-cell gene expression by quantitative reverse transcription-PCR and single-cell V(D)J sequencing. We found more frequent germinal center B cells in SQE than in Alum, albeit with a different gene expression profile. The V(D)J sequencing of W614A-3S-specific BCR showed significant differences in BCR sequences and validates the dichotomy between adjuvant formulations. All sixteen BCR sequences which were cloned were specific of peptide. Adjuvant formulations of W614A-3S-peptide-conjugated immunogen impact the quantity and quality of B cell immune responses at both the gene expression level and BCR sequence.
Funder
H2020 European Institute of Innovation and Technology
Fondation pour la Recherche Médicale
Subject
Immunology,Immunology and Allergy
Cited by
1 articles.
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