*Viruses* **2020**, *12*, 18

Of all these VLP insertions, HPV16 L1 VLPs displaying on the DE loop, L2 peptides representing aa 17–36 from HPV16 elicited antibodies that efficiently neutralized/protected against diverse HPV pseudovirus types (6/16/18/26/31/33/34/35/39/43/44/45/51/52/53/56/58/59/66/68/73) [69]. This is followed by HPV18 L1 VLPs displaying, on the DE loop and on the C-terminus, L2 peptides representing aa 17–36 from HPV33 and L2 peptides representing aa 56–75 from HPV58, respectively (Table 2). The VLPs protected rabbits from developing papillomas following challenge with diverse quasiviruses (6/11/16/18/31/35/39/45/59) [70]; the VLPs also protected mice from genital infection with HPV pseudoviruses (11/16/35/45/58/59). It is worth highlighting that HPV16 L1 VLPs displaying, between aa 130/433, L2 peptides representing aa 17–38 from HPV31 elicited antibodies that neutralized (to some degree) diverse HPV pseudovirus types (2/5/6/11/16/18/27/31/33/35/39/45/52/57/58/59/68) [72] (Table 2). Among the L2 insertions displayed on virus/virus-associated particles, Adeno-associated virus 2 VP3 virus particles displaying L2 peptides representing aa 17–36 from both HPV16 and HPV31 protected rabbits. The recombinant particles protected rabbits from developing papillomas following infection with eight different quasiviruses one year after immunization. Moreover, the rabbits did not develop papillomas for 10 weeks (the length of the study).

In summary, the type of peptide and the location of peptide insertion on eukaryotic VLPs make a difference in the neutralization potential. L2 peptide (aa 17–36) inserted on the DE loop elicits efficient broadly protective antibodies against diverse HPV types.
