tetano
Editor, Senior Moderator
Iran J Microbiol
. 2026 Oct;18(5):841-860.
doi: 10.18502/ijm.v18i5.22875.
Khabat Barkhordari 1 , Farhad Rezaei 1 , Vahid Salimi 1 , Kaveh Sadeghi 2 , Mostafa Alavi Moghadam 3 , Hossein Bagheri 4 , Masoumeh Pourjabali 5 , Maryam Karimi 6 , Omid Fotouhi 7 , Talat Mokhtari Azad 1
Affiliations Expand
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.
Keywords: DNA vaccine; H1N1 subtype; H3N2 subtype; Hemagglutinin; Influenza A virus.
. 2026 Oct;18(5):841-860.
doi: 10.18502/ijm.v18i5.22875.
A multi-epitope-based DNA vaccine confers cross-protection against influenza A H1N1 and H3N2 viruses
Khabat Barkhordari 1 , Farhad Rezaei 1 , Vahid Salimi 1 , Kaveh Sadeghi 2 , Mostafa Alavi Moghadam 3 , Hossein Bagheri 4 , Masoumeh Pourjabali 5 , Maryam Karimi 6 , Omid Fotouhi 7 , Talat Mokhtari Azad 1
Affiliations Expand
- PMID: 42992170
- PMCID: PMC13738242
- DOI: 10.18502/ijm.v18i5.22875
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.
Keywords: DNA vaccine; H1N1 subtype; H3N2 subtype; Hemagglutinin; Influenza A virus.