Portal de Periódicos da CAPES

Self-amplifying mRNA bicistronic influenza vaccines raise cross-reactive immune responses in mice and prevent infection in ferrets

2022; Cell Press; Volume: 27; Linguagem: Inglês

10.1016/j.omtm.2022.09.013

2329-0501

Cheng Chang, Nedzad Music, Michael Cheung, Evan Rossignol, Sukhmani Bedi, Harsh Patel, Mohammad Safari, Changkeun Lee, Gillis R. Otten, Ethan C. Settembre, Giuseppe Palladino, Yingxia Wen,

Viral gastroenteritis research and epidemiology

Vaccines are the primary intervention against influenza. Currently licensed inactivated vaccines focus immunity on viral hemagglutinin (HA). Self-amplifying mRNA (sa-mRNA) vaccines offer an opportunity to generate immunity to multiple viral proteins, including additional neuraminidase (NA). This evaluation of a bicistronic approach for sa-mRNA vaccine development compared subgenomic promoter and internal ribosome entry site strategies and found consistent and balanced expression of both HA and NA proteins in transfected cells. In mice, sa-mRNA bicistronic A/H5N1 vaccines raised potent anti-HA and anti-NA neutralizing antibody responses and HA- or NA-specific CD4+ and CD8+ T cell responses. The addition of NA also boosted the cross-neutralizing response to heterologous A/H1N1. Similar immunogenicity results were obtained for bicistronic seasonal A/H3N2 and B/Yamagata vaccines. In ferrets, sa-mRNA bicistronic A/H1N1 vaccine fully protected lung from infection by homologous virus and showed significant reduction of viral load in upper respiratory tract, warranting further evaluation of sa-mRNA bicistronic vaccine in humans.