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From antigenic drift to algorithmic prediction: Emerging paradigms in influenza vaccine design and global effectiveness (Review)

  • Authors:
    • Danyar Hamid Mohammed Amin
    • Dunya Hars Bapir
    • Bnar Rasul Abdarahman
    • Haider Hassan Khdr
    • Shadi Hamid Sidiq
    • Abdalla Ali Amin
    • Sirwan Khalid Ahmed
    • Rebwar Rzgar Qadir
  • View Affiliations / Copyright

    Affiliations: Department of Nursing, Raparin Technical and Vocational Institute, Rania, Sulaymaniyah, Kurdistan Region 46012, Iraq, College of Nursing, University of Raparin, Rania, Sulaymaniyah, Kurdistan Region 46012, Iraq, Department of Nursing, Raparin Technical and Vocational Institute, Rania, Sulaymaniyah, Kurdistan Region 46012, Iraq, Department of Medical Labs Technology, Raparin Technical and Vocational Institute, Rania, Sulaymaniyah, Kurdistan Region 46012, Iraq, Department of Chemistry, Faculty of Science and Health, Koya University, Koya, Kurdistan Region 46017, Iraq, College of Nursing, University of Raparin, Rania, Sulaymaniyah, Kurdistan Region 46012, Iraq
    Copyright: © Mohammed Amin et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
  • Article Number: 39
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    Published online on: March 26, 2026
       https://doi.org/10.3892/wasj.2026.454
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Abstract

Despite widespread annual vaccination efforts, seasonal influenza continues to represent a substantial global public health burden. The present comprehensive review critically discusses the virological, immunological and epidemiological determinants that constrain the effectiveness of contemporary influenza vaccines. A major challenge lies in the rapid evolutionary dynamics of the influenza virus, particularly through antigenic drift and, less frequently, antigenic shift, which frequently result in mismatches between vaccine strains and the circulating variant. The prolonged lead time required for vaccine production, based on early strain prediction, further increases the likelihood of such mismatches. Host‑related factors, including an advanced age, immunosenescence, obesity, comorbid conditions and immunological imprinting, contribute to marked variability in vaccine responsiveness across populations. Furthermore, the majority of currently available influenza vaccines predominantly elicit humoral immune responses, with the comparatively limited induction of cellular immunity, which is essential for durable and broad protection. The virus also employs multiple immune‑evasion strategies, including glycosylation masking and the suppression of interferon responses, further complicating vaccine effectiveness. Beyond biological constraints, factors such as vaccine hesitancy, inequitable access, and limitations in public health communication hinder vaccine uptake and the development of herd immunity. The present review further discusses emerging strategies, including mRNA vaccine platforms, broadly neutralizing antibodies, universal vaccine candidates targeting conserved viral epitopes and artificial‑intelligence0driven models for improved strain prediction. In conclusion, reducing the global burden of seasonal influenza will require an integrated approach that combines advances in vaccine technology with strengthened public health strategies, enhanced global surveillance and equitable vaccine access.
View Figures

Figure 1

Influenza virus variability and
pandemic potential: antigenic drift and shift. The image
illustrates the evolution of the influenza viruses through
antigenic drift and antigenic shift. (Left panel) Influenza virus
and seasonal variability: The image depicts influenza A (H1N1 and
H3N2) and B viruses, highlighting their key proteins, HA and NA,
which are targeted by the immune response. These proteins have high
mutation rates, necessitating frequent updates to vaccines. (Middle
panel) Antigenic drift and vaccine mismatch: This process involves
gradual mutations in the HA protein, particularly in antigenic
sites A-E, which can lead to mismatches between circulating strains
and vaccine strains, reducing vaccine effectiveness. (Right panel)
Antigenic shift and pandemic potential: Antigenic shift occurs when
the reassortment of viral genes leads to the emergence of novel
strains with the potential for cross-species transmission, such as
the swine-origin virus from the 2009 H1N1 pandemic. This process
increases the risk of pandemics. NA, neuraminidase; HA,
hemagglutinin.

Figure 2

Genetic changes in influenza viruses:
Antigenic drift and antigenic shift. The image illustrates the
genetic changes in influenza A viruses through antigenic shift and
antigenic drift. Avian H3Nx is a subtype of influenza A found in
birds, characterized by the H3 hemagglutinin protein and a variety
of neuraminidase (N) subtypes. It circulates in wild and domestic
birds and occasionally crosses species, posing a potential risk to
humans and other animals (160).
Seasonal Human H2N2 refers to a subtype that caused the 1957 Asian
flu pandemic. This strain, with H2 HA and N2 NA, circulated
seasonally until it was replaced by H3N2 in 1968 (161,162). Pandemic human H3N2 emerged in
1968, causing the Hong Kong flu pandemic, and resulted from a
reassortment event between avian and human influenza viruses. It
continues to circulate seasonally. Seasonal human H3N2 evolved from
the 1968 pandemic strain and continues to cause seasonal flu
infections, especially affecting vulnerable populations (163,164). NA, neuraminidase; HA,
hemagglutinin.
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Mohammed Amin DH, Bapir DH, Abdarahman BR, Khdr HH, Sidiq SH, Amin AA, Ahmed SK and Qadir RR: From antigenic drift to algorithmic prediction: Emerging paradigms in influenza vaccine design and global effectiveness (Review). World Acad Sci J 8: 39, 2026.
APA
Mohammed Amin, D.H., Bapir, D.H., Abdarahman, B.R., Khdr, H.H., Sidiq, S.H., Amin, A.A. ... Qadir, R.R. (2026). From antigenic drift to algorithmic prediction: Emerging paradigms in influenza vaccine design and global effectiveness (Review). World Academy of Sciences Journal, 8, 39. https://doi.org/10.3892/wasj.2026.454
MLA
Mohammed Amin, D. H., Bapir, D. H., Abdarahman, B. R., Khdr, H. H., Sidiq, S. H., Amin, A. A., Ahmed, S. K., Qadir, R. R."From antigenic drift to algorithmic prediction: Emerging paradigms in influenza vaccine design and global effectiveness (Review)". World Academy of Sciences Journal 8.3 (2026): 39.
Chicago
Mohammed Amin, D. H., Bapir, D. H., Abdarahman, B. R., Khdr, H. H., Sidiq, S. H., Amin, A. A., Ahmed, S. K., Qadir, R. R."From antigenic drift to algorithmic prediction: Emerging paradigms in influenza vaccine design and global effectiveness (Review)". World Academy of Sciences Journal 8, no. 3 (2026): 39. https://doi.org/10.3892/wasj.2026.454
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Spandidos Publications style
Mohammed Amin DH, Bapir DH, Abdarahman BR, Khdr HH, Sidiq SH, Amin AA, Ahmed SK and Qadir RR: From antigenic drift to algorithmic prediction: Emerging paradigms in influenza vaccine design and global effectiveness (Review). World Acad Sci J 8: 39, 2026.
APA
Mohammed Amin, D.H., Bapir, D.H., Abdarahman, B.R., Khdr, H.H., Sidiq, S.H., Amin, A.A. ... Qadir, R.R. (2026). From antigenic drift to algorithmic prediction: Emerging paradigms in influenza vaccine design and global effectiveness (Review). World Academy of Sciences Journal, 8, 39. https://doi.org/10.3892/wasj.2026.454
MLA
Mohammed Amin, D. H., Bapir, D. H., Abdarahman, B. R., Khdr, H. H., Sidiq, S. H., Amin, A. A., Ahmed, S. K., Qadir, R. R."From antigenic drift to algorithmic prediction: Emerging paradigms in influenza vaccine design and global effectiveness (Review)". World Academy of Sciences Journal 8.3 (2026): 39.
Chicago
Mohammed Amin, D. H., Bapir, D. H., Abdarahman, B. R., Khdr, H. H., Sidiq, S. H., Amin, A. A., Ahmed, S. K., Qadir, R. R."From antigenic drift to algorithmic prediction: Emerging paradigms in influenza vaccine design and global effectiveness (Review)". World Academy of Sciences Journal 8, no. 3 (2026): 39. https://doi.org/10.3892/wasj.2026.454
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