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Self-amplifying mRNA seasonal influenza vaccines elicit mouse neutralizing antibody and cell-mediated immunity and protect ferrets.
Cheung, Michael; Chang, Cheng; Rathnasinghe, Raveen; Rossignol, Evan; Zhang, Yunfei; Ferrari, Annette; Patel, Harsh; Huang, Yanjun; Sanchez Guillen, Michelle; Scalzo, Tina; Lee, Changkeun; Otten, Gillis R; Settembre, Ethan C; Music, Nedzad; Palladino, Giuseppe; Wen, Yingxia.
Afiliación
  • Cheung M; CSL Seqirus, 225 Wyman Street, Waltham, MA, 02451, USA.
  • Chang C; CSL Seqirus, 225 Wyman Street, Waltham, MA, 02451, USA.
  • Rathnasinghe R; CSL Seqirus, 225 Wyman Street, Waltham, MA, 02451, USA.
  • Rossignol E; CSL Seqirus, 225 Wyman Street, Waltham, MA, 02451, USA.
  • Zhang Y; CSL Seqirus, 225 Wyman Street, Waltham, MA, 02451, USA.
  • Ferrari A; CSL Seqirus, 225 Wyman Street, Waltham, MA, 02451, USA.
  • Patel H; CSL Seqirus, 225 Wyman Street, Waltham, MA, 02451, USA.
  • Huang Y; CSL Seqirus, 225 Wyman Street, Waltham, MA, 02451, USA.
  • Sanchez Guillen M; CSL Seqirus, 225 Wyman Street, Waltham, MA, 02451, USA.
  • Scalzo T; CSL Seqirus, 225 Wyman Street, Waltham, MA, 02451, USA.
  • Lee C; CSL Seqirus, 225 Wyman Street, Waltham, MA, 02451, USA.
  • Otten GR; CSL Seqirus, 225 Wyman Street, Waltham, MA, 02451, USA.
  • Settembre EC; CSL Seqirus, 225 Wyman Street, Waltham, MA, 02451, USA.
  • Music N; CSL Seqirus, 225 Wyman Street, Waltham, MA, 02451, USA.
  • Palladino G; CSL Seqirus, 225 Wyman Street, Waltham, MA, 02451, USA.
  • Wen Y; CSL Seqirus, 225 Wyman Street, Waltham, MA, 02451, USA. yingxia.wen@seqirus.com.
NPJ Vaccines ; 8(1): 150, 2023 Oct 04.
Article en En | MEDLINE | ID: mdl-37794051
Currently licensed influenza vaccines focus immune responses on viral hemagglutinin (HA), while the other major surface glycoprotein neuraminidase (NA) is not tightly controlled in inactivated vaccine formulations despite evidence that anti-NA antibodies reduce clinical disease. We utilized a bicistronic self-amplifying mRNA (sa-mRNA) platform encoding both HA and NA from four seasonal influenza strains, creating a quadrivalent influenza vaccine. sa-mRNA vaccines encoding an NA component induced the production of NA-inhibiting antibodies and CD4+ T-cell responses in both monovalent and quadrivalent formulations. Including NA in the vaccine enabled cross-neutralization against antigenically drifted strains and provided greater protection than HA alone upon A(H3N2) challenge in ferrets. These results demonstrate that next-generation bicistronic sa-mRNA vaccines expressing HA and NA induce potent antibodies against both viral coat proteins, as well as vaccine-specific cell-mediated immunity. When formulated as a quadrivalent seasonal influenza vaccine, the sa-mRNA platform provides an opportunity to increase the breadth of protection through cross-neutralizing anti-NA antibodies.

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: NPJ Vaccines Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: NPJ Vaccines Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido