Development of NP-Based Universal Vaccine for Influenza A Viruses
Ekramy E. Sayedahmed,
Nelly O. Elshafie,
Andrea P. dos Santos,
Chinnaswamy Jagannath,
Suryaprakash Sambhara,
Suresh K. Mittal
Affiliations
Ekramy E. Sayedahmed
Department of Comparative Pathobiology, Purdue Institute for Immunology, Inflammation and Infectious Disease, Purdue University Center for Cancer Research, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA
Nelly O. Elshafie
Department of Comparative Pathobiology, Purdue Institute for Immunology, Inflammation and Infectious Disease, Purdue University Center for Cancer Research, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA
Andrea P. dos Santos
Department of Comparative Pathobiology, Purdue Institute for Immunology, Inflammation and Infectious Disease, Purdue University Center for Cancer Research, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA
Chinnaswamy Jagannath
Department of Pathology and Genomic Medicine, Center for Infectious Diseases and Translational Medicine, Houston Methodist Research Institute, Weill-Cornell Medicine, Houston, TX 77030, USA
Suryaprakash Sambhara
Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA
Suresh K. Mittal
Department of Comparative Pathobiology, Purdue Institute for Immunology, Inflammation and Infectious Disease, Purdue University Center for Cancer Research, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA
The nucleoprotein (NP) is a vital target for the heterosubtypic immunity of CD8+ cytotoxic T lymphocytes (CTLs) due to its conservation among influenza virus subtypes. To further enhance the T cell immunity of NP, autophagy-inducing peptide C5 (AIP-C5) from the CFP10 protein of Mycobacterium tuberculosis was used. Mice were immunized intranasally (i.n.) with human adenoviral vectors, HAd-C5-NP(H7N9) or HAd-NP(H7N9), expressing NP of an H7N9 influenza virus with or without the AIP-C5, respectively. Both vaccines developed similar levels of NP-specific systemic and mucosal antibody titers; however, there was a significantly higher number of NP-specific CD8 T cells secreting interferon-gamma (IFN-γ) in the HAd-C5-NP(H7N9) group than in the HAd-NP(H7N9) group. The HAd-C5-NP(H7N9) vaccine provided better protection following the challenge with A/Puerto Rico/8/1934(H1N1), A/Hong Kong/1/68(H3N2), A/chukkar/MN/14951-7/1998(H5N2), A/goose/Nebraska/17097/2011(H7N9), or A/Hong Kong/1073/1999(H9N2) influenza viruses compared to the HAd-NP(H7N9) group. The autophagy transcriptomic gene analysis of the HAd-C5-NP(H7N9) group revealed the upregulation of some genes involved in the positive regulation of the autophagy process. The results support further exploring the use of NP and AIP-C5 for developing a universal influenza vaccine for pandemic preparedness.
