Protective immunity and safety of a genetically modified influenza virus vaccine

• Published in: PloS one Vol. 9; no. 6; p. e98685
• Main Authors: Barbosa, Rafael Polidoro Alves, Salgado, Ana Paula Carneiro, Garcia, Cristiana Couto, Filho, Bruno Galvão, Gonçalves, Ana Paula de Faria, Lima, Braulio Henrique Freire, Lopes, Gabriel Augusto Oliveira, Rachid, Milene Alvarenga, Peixoto, Andiara Cristina Cardoso, de Oliveira, Danilo Bretas, Ataíde, Marco Antônio, Zirke, Carla Aparecida, Cotrim, Tatiane Marques, Costa, Érica Azevedo, Almeida, Gabriel Magno de Freitas, Russo, Remo Castro, Gazzinelli, Ricardo Tostes, Machado, Alexandre de Magalhães Vieira
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13-06-2014; Public Library of Science (PLoS)
• Subjects: Animals; Biology and life sciences; CD8 antigen; Dogs; Emerging markets; Exo-a-sialidase; Gene Knockout Techniques; Genetic modification; Genetic vectors; Genetically modified organisms; Health aspects; Homeodomain Proteins - genetics; Homology; Immune response; Immune response (cell-mediated); Immunity; Immunity, Cellular - immunology; Immunization; Immunocompromised hosts; Infections; Inflammation; Inflammatory response; Influenza; Influenza A virus - enzymology; Influenza A virus - genetics; Influenza vaccines; Influenza Vaccines - genetics; Influenza Vaccines - immunology; Influenza viruses; Lethal dose; Lungs; Madin Darby Canine Kidney Cells; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; MyD88 protein; Myeloid Differentiation Factor 88 - genetics; Neuraminidase - genetics; Neuraminidase - immunology; Orthomyxoviridae Infections - immunology; Research and Analysis Methods; Safety; Safety and security measures; Vaccines; Vaccines, Synthetic - genetics; Vaccines, Synthetic - immunology; Vectors; Veterinary medicine; Viral Proteins - genetics; Viral Proteins - immunology; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0098685

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-Δ) 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-Δ 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.