Shing Jaimie Z, Porras Carolina, Pinheiro Maísa, Herrero Rolando, Hildesheim Allan, Liu Danping, Gail Mitchell H, Romero Byron, Schiller John T, Zúñiga Michael, Mishra Sambit, Burdette Laurie, Jones Kristine, Schussler John, Ocampo Rebeca, Fang Jianwen, Liu Zhiwei, Lowy Douglas R, Tsang Sabrina H, Rodríguez Ana Cecilia, Schiffman Mark, Haas Cameron B, Carvajal Loretto J, Brown Jalen R, Kreimer Aimée R, Mirabello Lisa
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Agencia Costarricense de Investigaciones Biomédicas (ACIB), formerly Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, San José, Costa Rica.
NPJ Vaccines. 2024 Jun 8;9(1):101. doi: 10.1038/s41541-024-00896-y.
The AS04-adjuvanted human papillomavirus (HPV)16/18 vaccine, an L1-based vaccine, provides strong vaccine efficacy (VE) against vaccine-targeted type infections, and partial cross-protection to phylogenetically-related types, which may be affected by variant-level heterogeneity. We compared VE against incident HPV31, 33, 35, and 45 detections between lineages and SNPs in the L1 region among 2846 HPV-vaccinated and 5465 HPV-unvaccinated women through 11-years of follow-up in the Costa Rica HPV Vaccine Trial. VE was lower against HPV31-lineage-B (VE=60.7%;95%CI = 23.4%,82.8%) compared to HPV31-lineage-A (VE=94.3%;95%CI = 83.7%,100.0%) (VE-ratio = 0.64;95%CI = 0.25,0.90). Differential VE was observed at several lineage-associated HPV31-L1-SNPs, including a nonsynonymous substitution at position 6372 on the FG-loop, an important neutralization domain. For HPV35, the only SNP-level difference was at position 5939 on the DE-loop, with significant VE against nucleotide-G (VE=65.0%;95%CI = 28.0,87.8) but not for more the common nucleotide-A (VE=7.4%;95%CI = -34.1,36.7). Because of the known heterogeneity in precancer/cancer risk across cross-protected HPV genotype variants by race and region, our results of differential variant-level AS04-adjuvanted HPV16/18 vaccine efficacy has global health implications.
AS04佐剂人乳头瘤病毒（HPV）16/18疫苗是一种基于L1的疫苗，对疫苗靶向型感染具有很强的疫苗效力（VE），并对系统发育相关型提供部分交叉保护，这可能受变异水平异质性的影响。在哥斯达黎加HPV疫苗试验中，我们对2846名接种HPV疫苗和5465名未接种HPV疫苗的女性进行了11年的随访，比较了L1区域中不同谱系和单核苷酸多态性（SNP）对HPV31、33、35和45感染的疫苗效力。与HPV31谱系A（VE=94.3%；95%CI=83.7%，100.0%）相比，针对HPV31谱系B的疫苗效力较低（VE=60.7%；95%CI=23.4%，82.8%）（VE比值=0.64；95%CI=0.25，0.90）。在几个与谱系相关的HPV31-L1-SNP中观察到了不同的疫苗效力，包括FG环上第6372位的非同义替换，这是一个重要的中和结构域。对于HPV35，唯一的SNP水平差异位于DE环上的第5939位，对核苷酸G有显著的疫苗效力（VE=65.0%；95%CI=28.0，87.8），但对更常见的核苷酸A则没有（VE=7.4%；95%CI=-34.1，36.7）。由于已知不同种族和地区的癌前病变/癌症风险在交叉保护HPV基因型变异中存在异质性，我们关于不同变异水平的AS04佐剂HPV16/18疫苗效力的结果具有全球健康意义。
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