Table 2.
Candidate eukaryotic VLP-based L2 HPV vaccines.
| Source of VLPs | HPV L2 Peptide Displayed (aa) | Length of Peptide | Position of Insertion on VLPs | Dose Immunized with | Neutralized or Protected against HPV Pseudoviruses (PsVs) * | Ref #. |
|---|---|---|---|---|---|---|
| HPV16 L1 | HPV16 L2 (aa 414–426) | 13 | Helix 4 loop (aa 414–426 replaced with L2) | Mice immunized with three doses of VLPs (100 μg/dose) | Assays not conducted; however, the peptide has been shown, in previous studies [63], to neutralize HPV 16 and HPV 6 | [64] |
| HPV16 L1 | HPV16 L2 (aa 18–38) | 21 | Helix 4 loop (between amino acids 430 and 433) | Rabbits immunized with five doses of VLPs (concentration not provided) | PsVs (neutralized): 16/18/31/52/58 | [65] |
| HPV16 L2 (aa 56–75) | 20 | PsVs (neutralized): 16/18/31/52/58 | ||||
| HPV16 L2 (aa 96–115) | 20 | PsVs (neutralized): 16/18/31/52/58 | ||||
| BPV1 | HPV16 L2 (aa 69–81) | 13 | Between amino acids 133 and 134 (DE loop) | Rabbits immunized with three doses of VLPs (50 μg/dose) | PsVs (neutralized): PsV11/PsV16 | [66] |
| HPV16 L2 (aa 108–120) | 13 | PsVs (neutralized): PsV11/PsV16 | ||||
| BPV1 | HPV16 L2 (aa 17–36) | 20 | Between amino acids 133 and 134 | Rabbits immunized with four doses of VLPs (25–50 μg/dose) | PsVs (neutralized): 5/16/18/45/58 | [67] |
| HPV16 L1 | HPV16 L2 (aa 17–36) | 20 | Between amino acids 136 and 137 (DE loop) | Rabbits immunized with four doses of VLPs (25–50 μg/dose) | PsVs (neutralized): 5/6/11/16/18/31/45/52/58/70 | [67,68] |
| Passive transferred sera protected mice against PsVs (genital): 6/16/18/26/31/33/34/35/39/43/44/45/51/52/53/56/58/59/66/68/73 | [69] | |||||
| Mice immunized with two doses of a mixture of 16L1 VLPs displaying 16L2 and HPV18 L1 VLPs (10 μg/dose) | PsV (genital): 58 | [68] | ||||
| HPV18 L1 | HPV33 L2 (aa 17–36) | 20 | Between amino acids 134 and 135 (DE loop) | Rabbits immunized with three doses of each VLP (20 μg/dose or 100 μg/dose) | QsV $ (neutralized): 5/6/11/18/16/31/33/45/52/58
QsVs (cutaneous): 11/18/58 |
[70] |
| HPV58 L2 (aa 56–75) | 20 | C-terminus | QsV (neutralized): 31/45 | |||
| HPV18 L1 | HPV33 L2 (aa 17–36) | 20 | HPV33 L2 inserted on DE loop and HPV58 L2 inserted on C-terminus | Rabbits immunized with three doses of a mixture of 18L1 VLPs displaying 33L2 on DE loop and 58L2 on C- terminus mixed human dose of 16L1/18L1 VLPs (Cervarix vaccine). Two μg/dose of chimeric 18L1-L2 and 1/10th per dose of Cervarix was used | QsVs (cutaneous): 6/11/16/18/31/35/39/45/59 | [70] |
| HPV58 L2 (aa 56–75) | 20 | Mice immunized with two of a mixture of 18L1 VLPs displaying 33L2 on DE loop and 58L2 on C- terminus mixed human dose of 16L1/18L1 VLPs (Cervarix vaccine). Two μg/dose of chimeric 18L1-L2 and 1/10th per dose of Cervarix was used | PsVs (genital): 11/16/35/45/58/59 | |||
| HPV18 L1 | HPV45 L2 (aa 16–35) | 20 | Between amino acids 134 and 135 | Rabbits immunized with five doses of VLPs (50 μg/dose) | Passive transferred sera protected mice against PsVs (genital): 16/18/39/45/59/68 | [71] |
| HPV16 L1 | HPV31 L2 (aa 17–38) | 22 | Helix 4 loop (between amino acids 430 and 433) | Mice immunized with four doses of VLPs (10 μg/dose) | PsVs (neutralized): 2/5/6/11/16/18/27/31/33/35/39/45/52/57/58/59/68 | [72] |
| Adeno- associated virus 2 VP3 virus particles | HPV16 L2 (aa 17–36) | 20 | HPV16 L2 inserted at position 587 and HPV31 L2 inserted at position 453 of VP3 | Mice immunized with three doses of particles (1 × 1011 per dose) | PsVs (neutralized): 16/18/31/45/52/58 | [73] |
| HPV31 L2 (aa 17–36) | 20 | Rabbits immunized with four doses of particles (2 × 1012 per dose) | PsVs (neutralized): 16/18/31/45/52/58 Passive transferred sera protected mice against PsVs (genital): 16 |
|||
| Adeno- associated virus 2 VP3 virus particles | HPV16 L2 (aa 17–36) | 20 | HPV16 L2 inserted at position 587 and HPV31 L2 inserted at position 453 of VP3 | Mice immunized with three doses of particles (1 × 1012 per dose) | PsVs (neutralized): 16/18/31/45/58 | [74] |
| HPV31 L2 (aa 17–36) | 20 | Rabbits immunized with three doses of particles (1 × 1019 per dose) | QsVs (cutaneous): 16/18/31/35/39/45/58/59 | |||
| Adenovirus type 5 | HPV16 L2 (12–41) | 30 | Hexon protein hypervariable regions 1 and 5 | Mice immunized with three doses of particles (1 × 1010 per dose) | PsVs (genital): 16/56 PsVs (neutralized): 16/73 |
[75] |
| Adenovirus type 35 | Concatemers of HPV: 6L2, 11L2, 16L2, 18L2, 31L2, 33L2, 45L2, 52L2, 58L2 (aa 17–36) | 60, 80, 100 | C-terminus of pIX | Mice immunized with two doses of particles (1 × 1010 per dose) | PsVs (neutralized): 16/18/31/59 | [76] |
| Hepatitis B core (HBc) VLPs | HPV16 L2 (aa 14–122) | 108 | Inserted between a heterodimer of HBc | Mice immunized with three doses of VLPs (5μg/dose) | PsVs (neutralized): 16 | [77] |
| Potato virus A VLPs | HPV16 L2 (aa 108–120) | 13 | L2 inserted on the N-terminus and E7 inserted on the C-terminus | Immunization studies not conducted | No studies | [78] |
| HPV16 E7 (aa 44–60) | 17 |
* Bolded PsVs indicate that protection/neutralization was both significant and complete, while PsVs not bolded (in black) indicate that although the protection/neutralization was significant, it was not complete. PsVs not bolded (in gray background) indicate that there was minimal protection/neutralization or no protection at all (not significant protection); # Ref: Reference; $ QsV: quasivirus (composed of HPV capsid and cottontail rabbit papillomavirus genome).