Abstract
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.
Highlights
Over 200 human papillomavirus (HPV) types, which are members of five genera (α, β, γ, μ, v) [1, 2], are responsible for approximately 5% of all human cancers and substantial precancerous and benign lesions [3, 4]
We found that vaccination with the HPV16L1-58L2 chimeric VLP (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, HPV18/39/45/59/68, HPV6/11, HPV2/27/57, and HPV5
Because HPV58 is highly prevalent in China, we have examined the potential of HPV58 L2 aa.15-37 (Figure 1, 100% identity with HPV52) to induce crosswww.impactjournals.com/oncotarget neutralizing antibodies and have generated HPV16L158L2 cVLP vaccine by inserting HPV58 L2 aa.16-37 into the DE surface loop of HPV16 L1 virus-like particle (VLP)
Summary
Over 200 human papillomavirus (HPV) types, which are members of five genera (α, β, γ, μ, v) [1, 2], are responsible for approximately 5% of all human cancers and substantial precancerous and benign lesions [3, 4]. Persistent infection with high-risk mucosal HPV (HPV 16/18/31/33/35/39/45/51/52/56/58/59/68/73/82 etc) is the etiological cause of most cervical cancer, which is the third most common cancer in women worldwide, and a proportion of other anogenital (vaginal, vulvar, penile and anal) and oropharyngeal cancers [5, 6]. While the nonavalent vaccine provides broader protection against oncogenic HPV infections and infection-related precancerous lesions, it still does not cover the cutaneous HPV types. High cost remains the primary challenge to global implementation of HPV vaccines, especially in the developing countries where nearly 90% of cervical cancer deaths occur [23, 24]
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