Yuste Eloisa, Gil Horacio, Garcia Felipe, Sanchez-Merino Victor
National Microbiology Center, Institute of Health Carlos III (ISCIII), 28220 Madrid, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), 28029 Madrid, Spain.
Vaccines (Basel). 2024 Oct 17;12(10):1176. doi: 10.3390/vaccines12101176.
BACKGROUND/OBJECTIVES: The impact of virion maturation on neutralizing antibody responses in HIV treatment is not fully understood. This study examines whether antiretroviral regimens (ART) with boosted protease inhibitors (b-PI), which increase exposure to immature virions, affect neutralization capacity compared to Non-b-PI regimens.
Neutralization activity was assessed in 45 HIV-infected individuals on b-PI regimens and 56 on Non-b-PI regimens, adjusting for factors like infection duration, ART initiation, and immune markers. Individuals on b-PI regimens had significantly lower neutralization scores [mean: 6.1, 95% Confidence Interval (CI): 5.3-6.9] than those on Non-b-PI regimens (mean: 8.9, 95% CI: 8.0-9.9; < 0.0001). This difference was not explained by infection duration or CD4+ counts. CD4+/CD8+ ratios were positively associated with neutralization, while b-PI use was negatively associated. A regression model indicated that b-PI use significantly predicted lower neutralization scores (beta = -0.30, = 0.049).
These findings suggest that exposure to immature virions via b-PI use reduces neutralizing antibody responses, highlighting the importance of virion maturation in antibody induction. ART regimens promoting exposure to mature virions may enhance neutralization, with potential implications for HIV vaccine design. Further research is needed to explore implications for HIV vaccine design, especially using virus-like particles.
背景/目的：病毒体成熟对HIV治疗中中和抗体反应的影响尚未完全明确。本研究旨在探讨使用增强型蛋白酶抑制剂（b-PI）的抗逆转录病毒疗法（ART），因其增加了未成熟病毒体的暴露，与非b-PI疗法相比，是否会影响中和能力。
对45名接受b-PI疗法的HIV感染者和56名接受非b-PI疗法的感染者进行中和活性评估，并对感染持续时间、ART起始时间和免疫标志物等因素进行校正。接受b-PI疗法的个体中和评分显著低于接受非b-PI疗法的个体（平均值：6.1，95%置信区间[CI]：5.3 - 6.9）（平均值：8.9，95%CI：8.0 - 9.9；<0.0001）。这种差异无法用感染持续时间或CD4 +细胞计数来解释。CD4+/CD8+比值与中和呈正相关，而使用b-PI则呈负相关。回归模型表明，使用b-PI可显著预测较低的中和评分（β = -0.30，= 0.049）。
这些发现表明，通过使用b-PI暴露于未成熟病毒体会降低中和抗体反应，凸显了病毒体成熟在抗体诱导中的重要性。促进暴露于成熟病毒体的ART方案可能会增强中和作用，这对HIV疫苗设计具有潜在意义。需要进一步研究以探讨其对HIV疫苗设计的影响，特别是使用病毒样颗粒方面。
