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oai:riubu.ubu.es:10259/83772024-01-18T01:05:23Zcom_10259_4862com_10259_5086com_10259_2604col_10259_4863

Influenza B Virus NS1-Truncated Mutants: Live-Attenuated Vaccine Approach Hai, Rong Martínez Sobrido, Luis Fraser, Kathryn A. Ayllón Barasoain, Juan García Sastre, Adolfo Palese, Peter Microbiología Medicina Biología molecular Microbiology Medicine Molecular biology Type B influenza viruses can cause substantial morbidity and mortality in the population, and vaccinationremains by far the best means of protection against infections with these viruses. Here, we report theconstruction of mutant influenza B viruses for potential use as improved live-virus vaccine candidates.Employing reverse genetics, we altered the NS1 gene, which encodes a type I interferon (IFN) antagonist. Theresulting NS1 mutant viruses induced IFN and, as a consequence, were found to be attenuated in vitro and invivo. The absence of pathogenicity of the NS1 mutants in both BALB/c and C57BL/6 PKR / mice wasconfirmed. We also provide evidence that influenza B virus NS1 mutants induce a self-adjuvanted immuneresponse and confer effective protection against challenge with both homologous and heterologous B virusstrains in mice. We thank Mark A. Yondola for helpful discussions and criticalreviewing. We also express our appreciation to Christopher Narbus,Lily Ngai, and Richard Cadagan for excellent technical assistance.This work was supported by grants from the NIH, R01 AI46954 (toA.G.-S.), U01 AI70469, and U19 AI62623 (Center for InvestigatingViral Immunity and Antagonism), and by CRIP (Center for Researchon Influenza Pathogenesis, NIAID contract HHSN266200700010C).K.A.F. was supported by NIH training grant T32 AI007647. 2024-01-17T13:11:12Z 2024-01-17T13:11:12Z 2008-11 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 0022-538X http://hdl.handle.net/10259/8377 10.1128/jvi.01213-08 1098-5514 eng Journal of Virology. 2008, V. 82, n. 21, p. 10580-10590 https://doi.org/10.1128/jvi.01213-08 info:eu-repo/semantics/openAccess application/pdf American Society for Microbiology