A novel candidate HPV vaccine: MS2 phage VLP displaying a tandem HPV L2 peptide offers similar protection in mice to Gardasil-9

- Epitopes within the HPV minor capsid protein (L2) are potentially broadly cross-type neutralizing.
- We have constructed novel recombinant VLPs that display multiple HPV L2 epitopes on the N-terminus of MS2 coat protein.
- MS2-31/16L2 VLPs are highly immunogenic in mice.
- Immunization with mixed MS2 VLPs displaying multiple L2 epitopes does not compromise the immunogenicity of individual epitopes.
- In a mouse challenge model, MS2-31/16L2 VLPs protect against six HPV types at levels similar to the Gardasil-9 vaccine.

Human papillomaviruses (HPVs) cause approximately 5% of cancer cases worldwide. Fortunately, three prophylactic vaccines have been approved to protect against HPV infections. Gardasil-9, the most recent HPV vaccine, is predicted to offer protection against the HPV types that cause ∼90% of cervical cancer, 86% of HPV-associated penile cancers, and ∼93% of HPV-associated head & neck cancers. As an alternative to Gardasil-9, we developed and tested a novel candidate vaccine targeting conserved epitopes in the HPV minor capsid protein, L2. We displayed a tandem HPV31/16L2 peptide (amino acid 17-31) or consensus peptides from HPV L2 (amino acid 69-86 or 108-122) on the surface of bacteriophage MS2 virus-like particles (VLPs). Mice immunized with the MS2 VLPs displaying the tandem peptide or immunized with a mixture of VLPs (displaying the tandem peptide and consensus peptide 69-86) elicited high titer antibodies against individual L2 epitopes. Moreover, vaccinated mice were protected from cervicovaginal infection with HPV pseudoviruses 16, 31, 45, 58 and sera from immunized mice neutralized HPV pseudoviruses 18 and 33 at levels similar to mice immunized with Gardasil-9. These results suggest that immunization with a tandem, L2 peptide or a low valency mixture of L2 peptide-displaying VLPs can provide broad protection against multiple HPV types.