Adenoviral Vector-Based Vaccine Expressing Hemagglutinin Stem Region with Autophagy-Inducing Peptide Confers Cross-Protection Against Group 1 and 2 Influenza A Viruses
<b>Background/Objectives:</b> An effective universal influenza vaccine is urgently needed to overcome the limitations of current seasonal influenza vaccines, which are ineffective against mismatched strains and unable to protect against pandemic influenza. <b>Methods:</b> In...
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MDPI AG
2025-01-01
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| author | Wen-Chien Wang Ekramy E. Sayedahmed Marwa Alhashimi Ahmed Elkashif Vivek Gairola Muralimanohara S. T. Murala Suryaprakash Sambhara Suresh K. Mittal |
| author_facet | Wen-Chien Wang Ekramy E. Sayedahmed Marwa Alhashimi Ahmed Elkashif Vivek Gairola Muralimanohara S. T. Murala Suryaprakash Sambhara Suresh K. Mittal |
| author_sort | Wen-Chien Wang |
| collection | DOAJ |
| description | <b>Background/Objectives:</b> An effective universal influenza vaccine is urgently needed to overcome the limitations of current seasonal influenza vaccines, which are ineffective against mismatched strains and unable to protect against pandemic influenza. <b>Methods:</b> In this study, bovine and human adenoviral vector-based vaccine platforms were utilized to express various combinations of antigens. These included the H5N1 hemagglutinin (HA) stem region or HA2, the extracellular domain of matrix protein 2 of influenza A virus, HA signal peptide (SP), trimerization domain, excretory peptide, and the autophagy-inducing peptide C5 (AIP-C5). The goal was to identify the optimal combination for enhanced immune responses and cross-protection. Mice were immunized using a prime-boost strategy with heterologous adenoviral (Ad) vectors. <b>Results:</b> The heterologous Ad vectors induced robust HA stem-specific humoral and cellular immune responses in the immunized mice. Among the tested combinations, Ad vectors expressing SP + HA stem + AIP-C5 conferred significant protection against group 1 (H1N1 and H5N1) and group 2 (H3N2) influenza A viruses. This protection was demonstrated by lower lung viral titers and reduced morbidity and mortality. <b>Conclusions:</b> The findings support further investigation of heterologous Ad vaccine platforms expressing SP + HA stem + AIP-C5. This combination shows promise as a potential universal influenza vaccine, providing broader protection against influenza A viruses. |
| format | Article |
| id | doaj-art-7847d477941d42c586418786d1cc8d5e |
| institution | Kabale University |
| issn | 2076-393X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj-art-7847d477941d42c586418786d1cc8d5e2025-01-24T13:51:55ZengMDPI AGVaccines2076-393X2025-01-011319510.3390/vaccines13010095Adenoviral Vector-Based Vaccine Expressing Hemagglutinin Stem Region with Autophagy-Inducing Peptide Confers Cross-Protection Against Group 1 and 2 Influenza A VirusesWen-Chien Wang0Ekramy E. Sayedahmed1Marwa Alhashimi2Ahmed Elkashif3Vivek Gairola4Muralimanohara S. T. Murala5Suryaprakash Sambhara6Suresh K. Mittal7Department of Comparative Pathobiology, Purdue Institute of Inflammation, Immunology and Infectious Disease, College of Veterinary Medicine, Purdue University, 625 Harrison St., West Lafayette, IN 47907, USADepartment of Comparative Pathobiology, Purdue Institute of Inflammation, Immunology and Infectious Disease, College of Veterinary Medicine, Purdue University, 625 Harrison St., West Lafayette, IN 47907, USADepartment of Comparative Pathobiology, Purdue Institute of Inflammation, Immunology and Infectious Disease, College of Veterinary Medicine, Purdue University, 625 Harrison St., West Lafayette, IN 47907, USADepartment of Comparative Pathobiology, Purdue Institute of Inflammation, Immunology and Infectious Disease, College of Veterinary Medicine, Purdue University, 625 Harrison St., West Lafayette, IN 47907, USADepartment of Comparative Pathobiology, Purdue Institute of Inflammation, Immunology and Infectious Disease, College of Veterinary Medicine, Purdue University, 625 Harrison St., West Lafayette, IN 47907, USADepartment of Comparative Pathobiology, Purdue Institute of Inflammation, Immunology and Infectious Disease, College of Veterinary Medicine, Purdue University, 625 Harrison St., West Lafayette, IN 47907, USAInfluenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30329, USADepartment of Comparative Pathobiology, Purdue Institute of Inflammation, Immunology and Infectious Disease, College of Veterinary Medicine, Purdue University, 625 Harrison St., West Lafayette, IN 47907, USA<b>Background/Objectives:</b> An effective universal influenza vaccine is urgently needed to overcome the limitations of current seasonal influenza vaccines, which are ineffective against mismatched strains and unable to protect against pandemic influenza. <b>Methods:</b> In this study, bovine and human adenoviral vector-based vaccine platforms were utilized to express various combinations of antigens. These included the H5N1 hemagglutinin (HA) stem region or HA2, the extracellular domain of matrix protein 2 of influenza A virus, HA signal peptide (SP), trimerization domain, excretory peptide, and the autophagy-inducing peptide C5 (AIP-C5). The goal was to identify the optimal combination for enhanced immune responses and cross-protection. Mice were immunized using a prime-boost strategy with heterologous adenoviral (Ad) vectors. <b>Results:</b> The heterologous Ad vectors induced robust HA stem-specific humoral and cellular immune responses in the immunized mice. Among the tested combinations, Ad vectors expressing SP + HA stem + AIP-C5 conferred significant protection against group 1 (H1N1 and H5N1) and group 2 (H3N2) influenza A viruses. This protection was demonstrated by lower lung viral titers and reduced morbidity and mortality. <b>Conclusions:</b> The findings support further investigation of heterologous Ad vaccine platforms expressing SP + HA stem + AIP-C5. This combination shows promise as a potential universal influenza vaccine, providing broader protection against influenza A viruses.https://www.mdpi.com/2076-393X/13/1/95human adenoviral vectorbovine adenoviral vectornonhuman adenoviral vectoradenoviral vectorhemagglutinin stemextracellular domain of matrix protein 2 |
| spellingShingle | Wen-Chien Wang Ekramy E. Sayedahmed Marwa Alhashimi Ahmed Elkashif Vivek Gairola Muralimanohara S. T. Murala Suryaprakash Sambhara Suresh K. Mittal Adenoviral Vector-Based Vaccine Expressing Hemagglutinin Stem Region with Autophagy-Inducing Peptide Confers Cross-Protection Against Group 1 and 2 Influenza A Viruses Vaccines human adenoviral vector bovine adenoviral vector nonhuman adenoviral vector adenoviral vector hemagglutinin stem extracellular domain of matrix protein 2 |
| title | Adenoviral Vector-Based Vaccine Expressing Hemagglutinin Stem Region with Autophagy-Inducing Peptide Confers Cross-Protection Against Group 1 and 2 Influenza A Viruses |
| title_full | Adenoviral Vector-Based Vaccine Expressing Hemagglutinin Stem Region with Autophagy-Inducing Peptide Confers Cross-Protection Against Group 1 and 2 Influenza A Viruses |
| title_fullStr | Adenoviral Vector-Based Vaccine Expressing Hemagglutinin Stem Region with Autophagy-Inducing Peptide Confers Cross-Protection Against Group 1 and 2 Influenza A Viruses |
| title_full_unstemmed | Adenoviral Vector-Based Vaccine Expressing Hemagglutinin Stem Region with Autophagy-Inducing Peptide Confers Cross-Protection Against Group 1 and 2 Influenza A Viruses |
| title_short | Adenoviral Vector-Based Vaccine Expressing Hemagglutinin Stem Region with Autophagy-Inducing Peptide Confers Cross-Protection Against Group 1 and 2 Influenza A Viruses |
| title_sort | adenoviral vector based vaccine expressing hemagglutinin stem region with autophagy inducing peptide confers cross protection against group 1 and 2 influenza a viruses |
| topic | human adenoviral vector bovine adenoviral vector nonhuman adenoviral vector adenoviral vector hemagglutinin stem extracellular domain of matrix protein 2 |
| url | https://www.mdpi.com/2076-393X/13/1/95 |
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