Table 1.
Different VHH formats and their functionality used to tackle various viral infections.
| VHH Format | Functionality | Virus | Reference |
Homobivalent VHHs
|
- Enhance and broaden antiviral activity | RSV Influenza Rabies HIV |
Hultberg et al. [21] Schepens et al. [55] Detalle et al. [56] Palomo et al. [57] Hultberg et al. [21] Cardoso et al. [52] Hufton et al. [18] Ibanez et al. [54] Hultberg et al. [21] Terryn et al. [45] Hulsik et al. [51] Matz et al. [53] |
| Bispecific VHHs - VHH linked to anti albumin VHH  - VHH linked to anti IgG VHH  - VHH linked to VHH which binds different epitopes on same target  |
- Half-life extension - Half-life extension - Enhance and broaden antiviral activity |
Rabies FMDV RSV Rabies HIV |
Terryn et al. [45] Harmsen et al. [30] Hultberg et al. [21] Hultberg et al. [21] Matz et al. [53] |
| VHH Format | Functionality | Virus | Reference |
PEGylation
|
- Half-life extension | FMDV | Harmsen et al. [34] |
VHH linked to IgG Fc region
|
- Half-life extension - Enhance and broaden antiviral activity - Effector function |
MERS Influenza HIV Rotavirus |
Raj et al. [48] Zhao et al. [20] Cardoso et al. [52] Laursen et al. [75] Bobkov et al. [68] Günaydın et al. [76] |
VHH linked to ferritin
|
- Half-life extension | Influenza | Fan et al. [32] |
VHH linked to GCN4
|
- Enhance and broaden antiviral activity | Influenza | Tillib et al. [58] |
VHH linked to COMP48
|
- Enhance and broaden antiviral activity | Rabies | Boruah et al. [59] |
VHH linked to IgG
|
- Effector function - Targeting |
HIV | Sun et al. [77] |
| VHH Format | Functionality | Virus | Reference |
VHH linked to cytotoxic domain
|
- Effector function | HSV-2 | Geoghegan et al. [78] |
VHH linked to liposome
|
- Effector function - Targeting |
HIV | Wang et al. [79] |
VHH linked to bacteria
|
- Targeting | Rotavirus | Pant et al. [80] Günaydın et al. [76] Alvarez et al. [81] |
VHH linked to GPI
|
- Targeting | HIV RSV |
Liu et al. [82] Tiwari et al. [83] |
VHH linked to cell-penetrating peptide
|
- Targeting | HCV | Thueng-in et al. [84] Phalaphol et al. [85] Glab-ampai et al. [86] Tarr et al. [87] |
VHHs, single-domain antibodies; RSV: human respiratory syncytial virus; HIV: human immunodeficiency virus; IgG: immunoglobulin G; PEG: Polyethylene glycol; FMDV: foot-and mouth disease virus; MERS CoV: Middle East respiratory syndrome coronavirus; GCN4: amino acid starvation-responsive transcription factor; COMP48: human cartilage oligomeric matrix protein; HSV-2: Herpes Simplex Virus-2; GPI: glycosylphosphatidylinositol; HCV: hepatitis C virus.