Pharmacokinetic tuning of protein–antigen fusions enhances the immunogenicity of T-cell vaccines

Menée in vitro et à l'aide de modèles murins, cette étude met en évidence l'intérêt d'une stratégie, consistant à fusionner des épitopes spécifiques de la tumeur à une protéine porteuse choisie en fonction de ses propriétés pharmacocinétiques, pour améliorer l'immunogénicité des vaccins sous-unitaires

Résumé en anglais

The formulations of peptide-based antitumour vaccines being tested in clinical studies are generally associated with weak potency. Here, we show that pharmacokinetically tuning the responses of peptide vaccines by fusing the peptide epitopes to carrier proteins optimizes vaccine immunogenicity in mice. In particular, we show in immunized mice that the carrier protein transthyretin simultaneously optimizes three factors: efficient antigen uptake in draining lymphatics from the site of injection, protection of antigen payloads from proteolytic degradation and reduction of antigen presentation in uninflamed distal lymphoid organs. Optimizing these factors increases vaccine immunogenicity by up to 90-fold and maximizes the responses to viral antigens, tumour-associated antigens, oncofetal antigens and shared neoantigens. Protein–peptide epitope fusions represent a facile and generalizable strategy for enhancing the T-cell responses elicited by subunit vaccines.