Translating innate response into long-lasting antibody response by the intrinsic antigen-adjuvant properties of papaya mosaic virus

利用木瓜花叶病毒的内在抗原佐剂特性将先天反应转化为持久的抗体反应

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作者:Elizabeth Acosta-Ramírez, Rebeca Pérez-Flores, Nathalie Majeau, Rodolfo Pastelin-Palacios, Cristina Gil-Cruz, Maricela Ramírez-Saldaña, Nataly Manjarrez-Orduño, Luisa Cervantes-Barragán, Leopoldo Santos-Argumedo, Leopoldo Flores-Romo, Ingeborg Becker, Armando Isibasi, Denis Leclerc, Constantino Lópe

Abstract

Identifying the properties of a molecule involved in the efficient activation of the innate and adaptive immune responses that lead to long-lasting immunity is crucial for vaccine and adjuvant development. Here we show that the papaya mosaic virus (PapMV) is recognized by the immune system as a pathogen-associated molecular pattern (PAMP) and as an antigen in mice (Pamptigen). A single immunization of PapMV without added adjuvant efficiently induced both cellular and specific long-lasting antibody responses. PapMV also efficiently activated innate immune responses, as shown by the induction of lipid raft aggregation, secretion of pro-inflammatory cytokines, up-regulation of co-stimulatory molecules on dendritic cells and macrophages, and long-lasting adjuvant effects upon the specific antibody responses to model antigens. PapMV mixed with Salmonella enterica serovar Typhi (S. typhi) outer membrane protein C increased its protective capacity against challenge with S. typhi, revealing the intrinsic adjuvant properties of PapMV in the induction of immunity. Antigen-presenting cells loaded with PapMV efficiently induced antibody responses in vivo, which may link the innate and adaptive responses observed. PapMV recognition as a Pamptigen might be translated into long-lasting antibody responses and protection observed. These properties could be used in the development of new vaccine platforms.

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