A multi-epitope-based DNA vaccine confers cross-protection against influenza A H1N1 and H3N2 viruses
7 affiliations
- 1Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
- 2Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- 3Department of Emergency Medicine, Imam Hossein Hospital, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- 4Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
- 5Department of Pathology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
- 6Department of Biostatistics, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- 7Science for Life Laboratory, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Solna, Sweden
Abstract
Background and Objectives:: Influenza A virus remains a major global health concern because antigenic drift reduces the long-term efficacy of current vaccines. This study evaluated a multi-epitope DNA vaccine targeting conserved regions of hemagglutinin (HA) and polymerase acidic (PA) proteins from influenza A/H1N1 and A/H3N2 viruses.
Materials and Methods:: Conserved B-cell, CD4+ T-cell, and CD8+ T-cell epitopes were identified using immunoinformatic tools and linked to β-defensin-2 in the pcDNA3.1(+) vector. Protein expression was confirmed in HEK293 cells. BALB/c mice were immunized intramuscularly and challenged with lethal doses of H1N1 or H3N2 viruses. Humoral and cellular immune responses, lung viral loads, histopathology, and clinical outcomes were assessed.
Results:: Vaccinated mice exhibited undetectable or markedly reduced lung viral loads (1,000–10,000-fold; p<0.01), significantly decreased pulmonary lesions, and milder clinical manifestations than controls. Vaccination induced significant CD4+ (p=0.041) and CD8+ (p=0.038) T-cell responses in bronchoalveolar lavage fluid, accompanied by increased interferon-γ and interleukin-4 production, indicating balanced cellular and humoral immunity. Complete protection against mortality was observed following viral challenge.
Conclusion:: This multi-epitope DNA vaccine elicited cross-protective immunity against influenza A/H1N1 and A/H3N2 by targeting conserved HA and PA epitopes, supporting its potential as a candidate for universal influenza vaccine development.
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BibTeX
@article{barkhordari2026multiepitopebased,
title = {{A multi-epitope-based DNA vaccine confers cross-protection against influenza A H1N1 and H3N2 viruses}},
author = {Khabat Barkhordari and Farhad Rezaei and Vahid Salimi and Kaveh Sadeghi and Mostafa Alavi Moghadam and Hossein Bagheri and Masoumeh Pourjabali and Maryam Karimi and Omid Fotouhi and Talat Mokhtari Azad},
journal = {Iranian Journal of Microbiology},
year = {2026},
month = nov,
doi = {10.18502/ijm.v18i5.22875},
url = {https://doi.org/10.18502/ijm.v18i5.22875},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - A multi-epitope-based DNA vaccine confers cross-protection against influenza A H1N1 and H3N2 viruses
AU - Khabat Barkhordari
AU - Farhad Rezaei
AU - Vahid Salimi
AU - Kaveh Sadeghi
AU - Mostafa Alavi Moghadam
AU - Hossein Bagheri
AU - Masoumeh Pourjabali
AU - Maryam Karimi
AU - Omid Fotouhi
AU - Talat Mokhtari Azad
PY - 2026
DA - 2026/11/06
JO - Iranian Journal of Microbiology
DO - 10.18502/ijm.v18i5.22875
UR - https://doi.org/10.18502/ijm.v18i5.22875
AB - Background and Objectives:: Influenza A virus remains a major global health concern because antigenic drift reduces the long-term efficacy of current vaccines. This study evaluated a multi-epitope DNA vaccine targeting conserved regions of hemagglutinin (HA) and polymerase acidic (PA) proteins from influenza A/H1N1 and A/H3N2 viruses. Materials and Methods:: Conserved B-cell, CD4+ T-cell, and CD8+ T-cell epitopes were identified using immunoinformatic tools and linked to β-defensin-2 in the pcDNA3.1(+) vector. Protein expression was confirmed in HEK293 cells. BALB/c mice were immunized intramuscularly and challenged with lethal doses of H1N1 or H3N2 viruses. Humoral and cellular immune responses, lung viral loads, histopathology, and clinical outcomes were assessed. Results:: Vaccinated mice exhibited undetectable or markedly reduced lung viral loads (1,000–10,000-fold; p<0.01), significantly decreased pulmonary lesions, and milder clinical manifestations than controls. Vaccination induced significant CD4+ (p=0.041) and CD8+ (p=0.038) T-cell responses in bronchoalveolar lavage fluid, accompanied by increased interferon-γ and interleukin-4 production, indicating balanced cellular and humoral immunity. Complete protection against mortality was observed following viral challenge. Conclusion:: This multi-epitope DNA vaccine elicited cross-protective immunity against influenza A/H1N1 and A/H3N2 by targeting conserved HA and PA epitopes, supporting its potential as a candidate for universal influenza vaccine development.
SN - 2008-3289
SN - 2008-4447
ER -