Department of Medicine, Division of Infectious Diseases and Immunology
Immunity | Immunoprophylaxis and Therapy | Influenza Virus Vaccines
Recombinant influenza viruses are promising viral platforms to be used as antigen delivery vectors. To this aim, one of the most promising approaches consists of generating recombinant viruses harboring partially truncated neuraminidase (NA) segments. To date, all studies have pointed to safety and usefulness of this viral platform. However, some aspects of the inflammatory and immune responses triggered by those recombinant viruses and their safety to immunocompromised hosts remained to be elucidated. In the present study, we generated a recombinant influenza virus harboring a truncated NA segment (vNA-Delta) and evaluated the innate and inflammatory responses and the safety of this recombinant virus in wild type or knock-out (KO) mice with impaired innate (Myd88 -/-) or acquired (RAG -/-) immune responses. Infection using truncated neuraminidase influenza virus was harmless regarding lung and systemic inflammatory response in wild type mice and was highly attenuated in KO mice. We also demonstrated that vNA-Delta infection does not induce unbalanced cytokine production that strongly contributes to lung damage in infected mice. In addition, the recombinant influenza virus was able to trigger both local and systemic virus-specific humoral and CD8+ T cellular immune responses which protected immunized mice against the challenge with a lethal dose of homologous A/PR8/34 influenza virus. Taken together, our findings suggest and reinforce the safety of using NA deleted influenza viruses as antigen delivery vectors against human or veterinary pathogens.
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© 2014 Barbosa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI of Published Version
PLoS One. 2014 Jun 13;9(6):e98685. doi: 10.1371/journal.pone.0098685. eCollection 2014. Link to article on publisher's site
Barbosa, Rafael Polidoro Alves; Salgado, Ana Paula Carneiro; Garcia, Cristiana Couto; Filho, Bruno Galvao; Goncalves, Ana Paula de Faria Paula de Faria; Lima, Braulio Henrique Freire; Lopes, Gabriel Augusto Oliveira; Rachid, Milene Alvarenga; Peixoto, Andiara Cristina Cardoso; de Oliveira, Danilo Bretas; Ataide, Marco Antonio; Zirke, Carla Aparecida; Cotrim, Tatiane Marques; Costa, Erica Azevedo; Almeida, Gabriel Magno de Freitas; Russo, Remo Castro; Gazzinelli, Ricardo T.; and Vieira Machado, Alexandre de Magalhaes, "Protective immunity and safety of a genetically modified influenza virus vaccine" (2014). University of Massachusetts Medical School Faculty Publications. 424.
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