Studies of flagellin fusion proteins for influenza vaccination.
| Ref | Antigen/epitope | Epitope location and adjuvant | Species/route of admin | Summary of observed immune responses and results |
|---|---|---|---|---|
| [92] | 11–15 a.a. B-cell, Th, and CTL epitopes from HA or NP | HV, none | Mice, i.n. | Flagellins containing viral T-cell epitopes induce T-cell proliferation ex vivo and confer 100% protection from a lethal dose of influenza in mice up to 7 months post vaccination |
| [93] | 11–15 a.a. B-cell, Th, and CTL epitopes from HA or NP | HV, none | Mice, i.n. | Pre-immunisation with unmodified flagellin to induce immunity to the carrier protein had no effect on the efficacy of flagellin fusion vaccines given subsequently |
| [69] | 11–15 a.a. B-cell, Th, and CTL epitopes from HA or NP | HV, none | Mice, i.n. | Induction of virus-specific IgG, splenocyte proliferation, and production of IL-2/IFN-γ, reduced viral titres in the lung, and protection from sub-lethal influenza challenge |
| [94] | 24 a.a. from matrix protein M2 ectodomain | C-term, none | Mice, s.c. or i.n. | M2e-specific antibody responses lasting at least 10 months protected mice from a lethal challenge with influenza A virus, with efficacy comparable between s.c. or i.n. delivery |
| [14] | 175–271 a.a. from HA globular head domains | C-term, none | Mice, s.c. | Induction of HA-specific antibodies and protection from lethal challenge with mouse-adapted influenza PR8 virus |
| [78] | 222 a.a. from HA1 globular head domain | C-term, none | Human, i.m. | A single dose up to 8 μg was well tolerated with no serious adverse events, increased titre of anti-HA1 antibodies lasting at least 6 months |
| [30] | 222 a.a. from HA1 globular head domain | C-term, none | Human, i.m. | A single dose of 5 μg was well tolerated and induced a > 10-fold increase in HA1 antibody levels and seroprotection in elderly subjects |
| [89] | 222 a.a. from HA1 globular head domain | C-term & HV, none | Human, i.m. | A single dose of 1.25 or 2.5 μg was well tolerated, inducing a 19-fold increase in anti-HA antibodies by day 21 in 97 subjects aged 18–64 |
| [95] | Various epitopes from HA1 globular head domain | C-term & HV, none | Human, i.m. | A single dose of any of 4 flagellin fusions with HA1 attached at either the D3 domain or the C-terminus increased anti-HA1 titres by day 21 in adults aged 18–40 |
| [5] | 222 a.a. from HA1-2 globular head domain | N-term, none | Mice, i.p. | Boosts at 14 and 28 days elicited robust HA1-2-specific serum IgG1 and IgG2a titers lasting for at least 3 months post-immunisation |
| [47] | Various epitopes from matrix protein 2 or HA2 domain | HV, none | Mice, i.n. | Three different flagellin fusion proteins were cross-linked to form nanoparticles, immunized mice were fully protected against lethal doses of viral challenge |
| [48] | 22 a.a. from M2e and 33 a.a. from helix C of HA stalk | N-term, none | Mice, i.m. | Flagellin was further modified with a coiled-coil domain to produce self-assembling nanoparticles, boosts at days 14 and 28, full protection from lethal viral challenge |
| [40] | Various epitopes from M2e and HA2-2 | C-term & HV, none | Mice, s.c. | Flagellins containing both M2e and MA2-2 epitopes induced strong IgG, CD4+, and CD8+ T-cell responses to target antigens, and protection from lethal viral challenge |
All antigens reported in Table 1 were expressed in E. coli, indicating that glycosylation of the antigen is not necessary to elicit immunoprotection. There was no use of additional adjuvant beyond flagellin itself in these studies. C-term: C-terminus; CTL: cytotoxic T-cell; HA: hemagglutinin; HV: hypervariable; IFN: interferon; i.m.: intramuscular; i.n.: intranasal; i.p.: intraperitoneal; M2e: matrix protein 2 extracellular domain; NP: nucleoprotein; N-term: N-terminus; s.c.: subcutaneous.
CE: Writing—original draft, Writing—review & editing. The author read and approved the submitted version.
The author declares that there are no conflicts of interest.
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