Department of Pathology, Johns Hopkins University, 1550 Orleans St, Baltimore, MD, 21287, United States.
Department of Biostatistics, Johns Hopkins University, 550 N Broadway, Baltimore, MD, 21205, United States.
Virology. 2022 Oct;575:63-73. doi: 10.1016/j.virol.2022.08.006. Epub 2022 Aug 23.
Human alphapapillomaviruses (αHPV) infect genital mucosa, and a high-risk subset is a necessary cause of cervical cancer. Licensed L1 virus-like particle (VLP) vaccines offer immunity against the nine most common αHPV associated with cervical cancer and genital warts. However, vaccination with an αHPV L2-based multimer vaccine, α11-88x5, protected mice and rabbits from vaginal and skin challenge with diverse αHPV types. While generally clinically inapparent, human betapapillomaviruses (βHPV) are possibly associated with cutaneous squamous cell carcinoma (CSCC) in epidermodysplasia verruciformis (EV) and immunocompromised patients. Here we show that α11-88x5 vaccination protected wild type and EV model mice against HPV5 challenge. Passive transfer of antiserum conferred protection independently of Fc receptors (FcR) or Gr-1+ phagocytes. Antisera demonstrated robust antibody titers against ten βHPV by L1/L2 VLP ELISA and neutralized and protected against challenge by 3 additional βHPV (HPV49/76/96). Thus, unlike the licensed vaccines, α11-88x5 vaccination elicits broad immunity against αHPV and βHPV.
人类α型乳头瘤病毒（αHPV）感染生殖器黏膜，高危型别是宫颈癌的必要病因。已获许可的 L1 病毒样颗粒（VLP）疫苗可预防与宫颈癌和生殖器疣相关的 9 种最常见的 αHPV。然而，基于 αHPV L2 的多聚体疫苗α11-88x5 对阴道和皮肤的多种 αHPV 类型的挑战具有保护作用，可保护小鼠和兔子免受感染。虽然一般在临床上无明显症状，但人类β型乳头瘤病毒（βHPV）可能与疣状表皮发育不良（EV）和免疫功能低下患者的皮肤鳞状细胞癌（CSCC）有关。在这里，我们表明 α11-88x5 疫苗接种可保护野生型和 EV 模型小鼠免受 HPV5 的挑战。抗血清的被动转移可独立于 Fc 受体（FcR）或 Gr-1+吞噬细胞提供保护。抗血清通过 L1/L2 VLP ELISA 对十种 βHPV 显示出强大的抗体滴度，并中和和保护免受另外三种 βHPV（HPV49/76/96）的挑战。因此，与已许可的疫苗不同，α11-88x5 疫苗接种可引发针对 αHPV 和 βHPV 的广泛免疫。
