Human papillomavirus 16L1-58L2 chimeric virus-like particles elicit durable neutralizing antibody responses against a broad-spectrum of human papillomavirus types

The neutralizing antibodies elicited by human papillomavirus (HPV) major capsid protein L1 virus-like particle (VLP)-based vaccines are largely type-specific. An HPV vaccine inducing cross-neutralizing antibodies broadly will be cost-effective and of great value. To this end, we constructed HPV16L1-58L2 chimeric VLP (cVLP) by displaying HPV58 L2 aa.16-37 on the DE surface region of HPV16 L1. We found that vaccination with the HPV16L1-58L2 cVLP formulated with alum plus monophosphoryl lipid A (Alum-MPL) adjuvant elicited robust neutralizing antibodies in both mice and rabbits against all tested HPV types including HPV16/31/33/35/52/58 (genus α9), HPV18/39/45/59/68 (genus α7), HPV6/11 (genus α10), HPV2/27/57 (genus α4), and HPV5 (genus β1). Importantly, the cross-neutralizing antibody response was maintained at least 82 weeks in mice or 42 weeks in rabbits, and complete protection against HPV58 was observed at week 85 in mice. Our data demonstrate that HPV16L1-58L2 cVLP is an excellent pan-HPV vaccine candidate.