Han Zhenwei, Wang Shen, Mu Ting, Zhao Ping, Song Lingli, Zhang Ying, Zhao Jin, Yin Wen, Wu Yue, Wang Huan, Gong Bo, Ji Min, Roden Richard B S, Yang Yanping, Klein Michel, Wu Ke
Project Management Department, Wuhan BravoVax Co., Ltd., Wuhan 430070, China.
State Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Key Laboratory of Industrial Biotechnology, School of Life Sciences, Hubei University, Wuhan 430062, China.
Vaccines (Basel). 2024 Jun 20;12(6):689. doi: 10.3390/vaccines12060689.
Human papillomavirus (HPV) is a prevalent cause of mucosal and cutaneous infections and underlying conditions ranging from benign warts to anogenital and oropharyngeal cancers affecting both males and females, notably cervical cancer. Cervical cancer is the fourth leading cause of cancer deaths among women globally and is the most impactful in low- and middle-income countries (LMICs), where the costs of screening and licensed L1-based HPV vaccines pose significant barriers to comprehensive administration. Additionally, the licensed L1-based HPV vaccines fail to protect against all oncogenic HPV types. This study generated three independent lots of an L2-based target antigen (LBTA), which was engineered from conserved linear L2-protective epitopes (aa11-88) from five human alphapapillomavirus genotypes in under cGMP conditions and adjuvanted with aluminum phosphate. Vaccination of rabbits with LBTA generated high neutralizing antibody titers against all 17 HPV types tested, surpassing the nine types covered by Gardasil9. Passive transfer of naïve mice with LBTA antiserum revealed its capacity to confer protection against vaginal challenge with all 17 αHPV types tested. LBTA shows stability at room temperature over >1 month. Standard and toxicology studies suggest a promising safety profile. These findings suggest LBTA's promise as a next-generation vaccine with comprehensive coverage aimed at reducing the economic and healthcare burden of cervical and other HPV+ cancers in LMICs, and it has received regulatory approval for a first-in-human clinical study (NCT05672966).
人乳头瘤病毒(HPV)是黏膜和皮肤感染以及多种潜在病症的常见病因,这些病症涵盖从良性疣到影响男性和女性的肛门生殖器及口咽癌,宫颈癌尤为突出。宫颈癌是全球女性癌症死亡的第四大主要原因,在低收入和中等收入国家(LMICs)影响最为严重,在这些国家,筛查成本以及已获许可的基于L1的HPV疫苗构成了全面接种的重大障碍。此外,已获许可的基于L1的HPV疫苗无法预防所有致癌性HPV类型。本研究在cGMP条件下,利用来自五种人α乳头瘤病毒基因型的保守线性L2保护性表位(aa11 - 88)构建了三个独立批次的基于L2的靶抗原(LBTA),并佐以磷酸铝。用LBTA对兔子进行免疫接种后,产生了针对所有17种测试HPV类型的高中和抗体滴度,超过了九价重组人乳头瘤病毒疫苗(Gardasil9)所涵盖的九种类型。用LBTA抗血清对未接触过抗原的小鼠进行被动转移,结果显示其能够对所有17种测试的αHPV类型的阴道攻击提供保护。LBTA在室温下超过1个月仍保持稳定。标准和毒理学研究表明其安全性良好。这些发现表明LBTA有望成为一种具有全面覆盖范围的下一代疫苗,旨在减轻低收入和中等收入国家宫颈癌及其他HPV相关癌症的经济和医疗负担,并且它已获得首次人体临床试验的监管批准(NCT05672966)。