HPV Vaccine Trial

HPV 疫苗试验

• 批准号: 10919010
• 负责人: Aimee Kreimer
• 金额: $ 370.04万
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10919010
• 关键词: Acquired Immunodeficiency Syndrome; Age; Antibodies; Antibody Avidity; Anus; Blinded; Cervical; Cervix Neoplasms; Cervix Uteri; Clinical; Collaborations; Communities; Costa Rica; Cytology; DNA; Dose; Effectiveness; Enrollment; Evaluation; Frequencies; Funding; HIV Infections; HIV Seropositivity; HPV-16/18 Vaccine; Head and Neck Cancer; Human Papilloma Virus Vaccination; Human Papilloma Virus Vaccine; Human Papilloma Virus-Related Malignant Neoplasm; Human Papillomavirus; Human papilloma virus infection; Human papillomavirus 16; Human papillomavirus 18; Immune response; Immunologics; Infection; Lesion; Malignant Neoplasms; Malignant neoplasm of anus; Malignant neoplasm of cervix uteri; Measures; Medical; Methodology; Molecular Conformation; Natural History; Oncogenic; Participant; Phase; Phylogenetic Analysis; Population; Population Group; Preventative vaccination; Public Health; Randomized; Randomized, Controlled Trials; Research; Resource-limited setting; Safety; Series; Site; Structural Protein; System; United States National Institutes of Health; Vaccinated; Vaccination; Vaccinee; Vaccines; Viral; Virus-like particle; Woman; Women' s Health; Work; dosage; efficacy evaluation; follow-up; high risk; immunogenic; immunogenicity; infection rate; men who have sex with men; oral HPV-positive head and neck cancers; premalignant; prevent; screening program; self assembly; unvaccinated; vaccine formulation; vaccine trial; virtual

Infections with oncogenic types of HPV cause virtually all cases of cervical cancer worldwide and subsets of various other anogenital and head and neck cancers. Prophylactic vaccination against HPV-16 and HPV-18, two of the most important HPV types, could protect against a large majority of the cases of cervical cancer globally and a considerable proportion of other HPV-associated cancers. Vaccines based on the L1 structural protein of HPV that self-assemble into conformationally-correct VLPs have been shown to be generally safe, immunogenic and effective at preventing precancerous lesions of the cervix associated with HPV-16/18. A community-based phase 3 randomized controlled trial of an HPV16/18 VLP vaccine was conducted in Costa Rica. Costa Rica was chosen for the trial because of our extensive successful scientific collaborations there, the high risk of cervical cancer, the universal medical system providing national linkage, and the likelihood of very high participation over the many needed years of close clinical follow-up. Randomization and 3-dose vaccination of 7,466 women enrolled into the HPV-16/18 Vaccine Trial in Costa Rica has been successfully completed. Women have been followed actively on an annual or semi-annual basis in the first four years of follow-up and every two years thereafter. Women have completed their first four years of follow-up in the blinded phase of the trial and have been enrolled in the extended (up to 10 years) follow-up phase of the study. Cross-over vaccination was offered to trial participants at the end of the four-year blinded phase of the trial. Results from this study have shown that 1) the vaccine is highly effective at preventing new infections with HPV types 16 or 18, 2) the vaccine confers partial protection against HPV types phylogenetically related to HPV 16 or 18, 3) the vaccine does not help treat existing infections, 4) fewer than 3 doses of the vaccine protects as well as the full 3-dose series for at least 4 years, 5) the vaccine protects against HPV infection at the anus, 6) Vaccine impact declines with increasing age at vaccination, 7) vaccination induces cross-neutralizing potential in sera of vaccinated individuals, 8) modest levels of antibodies generated by natural HPV infection provide partial protection against re-infection, and 9) antibody levels generated in vaccines from regions with high HIV infection rates are comparable to those observed among participants in our trial in Costa Rica. In support of the vaccine trials, a variety of methodologic and ancillary projects are underway or planned, that will maximize the yield of the main effort. This includes evaluation of immunological correlates of protection, including viral neutralization, total type-specific antibodies, and measures of antibody avidity. Immunological correlates of protection among naturally infected women are being examined and studies are underway to better understand why vaccinated women might be protected against HPV types not included in the vaccine formulation and why a single vaccine dose (prime-only) appears to protect for several years. Several analyses are underway or planned to evaluate the natural history of HPV infection at cervical and other sites and of cervical neoplasia in vaccinated and unvaccinated women. This effort is sponsored by Intramural NCI funds and by the NIH Office of Research on Women's Health (ORWH). It was formerly associated with Project Z01 CP010177.

感染致癌类型的HPV几乎会导致全世界所有的宫颈癌病例以及其他各种肛门癌和头颈癌的亚型。预防接种HPV-16和HPV-18这两种最重要的HPV类型，可以预防全球绝大多数宫颈癌病例和相当大比例的其他HPV相关癌症。基于HPV L1结构蛋白的疫苗自组装成构象正确的VLP，已被证明总体上是安全的，具有免疫原性，在预防与HPV-16/18相关的宫颈癌前病变方面有效。一项基于社区的HPV16/18 VLP疫苗的第三阶段随机对照试验在哥斯达黎加进行。之所以选择哥斯达黎加进行试验，是因为我们在那里进行了广泛的成功的科学合作，宫颈癌的高风险，提供国家联系的全民医疗系统，以及在所需的多年密切临床随访中非常高的参与率。在哥斯达黎加参加HPV-16/18疫苗试验的7466名妇女的随机和三剂疫苗接种工作已经顺利完成。在头四年的后续行动中，每年或每半年积极跟踪监测妇女情况，此后每两年跟踪监测一次。妇女已经在试验的盲目阶段完成了头四年的跟踪，并参加了研究的延长(最多10年)后续阶段。在为期四年的盲目试验阶段结束时，向试验参与者提供交叉疫苗接种。这项研究的结果表明，1)疫苗在预防新感染HPV16或18型方面非常有效，2)疫苗提供了对与HPV16或18的系统发育相关的HPV型的部分保护，3)疫苗无助于治疗现有的感染，4)少于3剂的疫苗保护以及至少4年的完整3剂系列的保护，5)疫苗保护肛门处的HPV感染，6)疫苗接种时随着年龄的增长疫苗影响力下降，7)疫苗接种诱导被接种个体的血清中交叉中和潜力，8)由自然HPV感染产生的中等水平的抗体提供了对再次感染的部分保护，以及9)来自艾滋病毒感染率高的地区的疫苗产生的抗体水平与我们在哥斯达黎加的试验参与者中观察到的抗体水平相当。为了支持疫苗试验，正在进行或计划进行各种方法和辅助项目，以最大限度地提高主要工作的产量。这包括评估保护性的免疫学相关性，包括病毒中和、总类型特异性抗体和抗体亲和力的测量。正在审查自然感染妇女中保护的免疫学相关性，并正在进行研究，以更好地了解为什么接种疫苗的妇女可能对疫苗配方中未包括的HPV类型具有保护作用，以及为什么一剂疫苗(仅优质疫苗)似乎可以保护数年。正在进行或计划进行一些分析，以评估宫颈和其他部位的HPV感染以及接种疫苗和未接种疫苗的妇女宫颈肿瘤的自然病史。这项工作由NCI内部基金和NIH妇女健康研究办公室(ORWH)赞助。它以前与项目Z01 CP010177相关联。

项目成果

Analysis of cervical HPV infections among unvaccinated young adult women to inform vaccine strategies in this age group: the Costa Rica HPV Vaccine Trial.

• DOI: 10.1136/sextrans-2022-055434
• 发表时间: 2022-07-16
• 期刊: Sexually transmitted infections
• 影响因子: 3.6

HPV vaccination initiation after the routine-recommended ages of 11-12 in the United States.

• DOI: 10.1016/j.pvr.2015.12.001
• 发表时间: 2016-12-01
• 期刊: Papillomavirus research (Amsterdam, Netherlands)
• 作者: Beachler DC;Gonzales FA;Kobrin SC;Kreimer AR
• 通讯作者: Kreimer AR

The Natural History of Oral Human Papillomavirus in Young Costa Rican Women.

• DOI: 10.1097/olq.0000000000000625
• 发表时间: 2017-07
• 期刊: Sexually transmitted diseases
• 影响因子: 3.1
• 作者: Beachler DC;Lang Kuhs KA;Struijk L;Schussler J;Herrero R;Porras C;Hildesheim A;Cortes B;Sampson J;Quint W;Gonzalez P;Kreimer AR
• 通讯作者: Kreimer AR

Comparing one dose of HPV vaccine in girls aged 9-14 years in Tanzania (DoRIS) with one dose of HPV vaccine in historical cohorts: an immunobridging analysis of a randomised controlled trial.

• DOI: 10.1016/s2214-109x(22)00306-0
• 发表时间: 2022-10
• 期刊: LANCET GLOBAL HEALTH
• 影响因子: 34.3
• 作者: Baisley, Kathy;Kemp, Troy J.;Kreimer, Aimee R.;Basu, Partha;Changalucha, John;Hildesheim, Allan;Porras, Carolina;Whitworth, Hilary;Herrero, Rolando;Lacey, Charles J.;Schiller, John T.;Lucas, Eric;Mutani, Paul;Dillner, Joakim;Indangasi, Jackton;Muwonge, Richard;Hayes, Richard J.;Pinto, Ligia A.;Watson-Jones, Deborah
• 通讯作者: Watson-Jones, Deborah

Prioritisation of the human papillomavirus vaccine in a time of constrained supply.

在供应紧张的情况下优先考虑人乳头瘤病毒疫苗。

• DOI: 10.1016/s2352-4642(20)30038-9
• 发表时间: 2020
• 期刊: The Lancet. Child & adolescent health
• 作者: Kreimer,AiméeR;Cernuschi,Tania;Rees,Helen;Saslow,Debbie;Porras,Carolina;Schiller,John
• 通讯作者: Schiller,John