Urueña A, Badano M N, Baré P, González J, Vicentín R, Calli R, Cañero-Velasco M C, Fink S, Vizzotti C
ISALUD University, Centro de Estudios para la Prevención y Control de Enfermedades Transmisibles, Venezuela 931 C1095AAS, Ciudad Autónoma de Buenos Aires, Argentina.
Instituto de Medicina Experimental (IMEX)-CONICET. Academia Nacional de Medicina., Laboratorio de Patogenia de Infecciones Virales, Av. Gral. Las Heras 3092, C1425ASU Ciudad Autónoma de Buenos Aires, Argentina.
Vaccine. 2022 Jan 3;40(1):114-121. doi: 10.1016/j.vaccine.2021.11.037. Epub 2021 Nov 24.
Infants' universal hepatitis A virus (HAV) single-dose vaccination has been highly effective for controlling HAV infection in Argentina, and in other Latin-American countries that adopted that strategy. Although antibodies wane over time, this has not been associated with HAV outbreaks or breakthrough infections, suggesting a relevant role for memory immunity. This study assessed long term humoral and cellular immune memory response after an average of 12 years follow-up of HAV single-dose vaccination. We selected 81 HAV-single dose vaccinated individuals from a 2015 study, including 54 with unprotective (UAL) and 27 with protective antibody levels (PAL) against HAV. Humoral memory response was assessed by measuring anti-HAV antibody titers at admission in both groups, and 30 days after a booster dose in the UAL group. Flow cytometry analysis of peripheral blood mononuclear cell samples stimulated with HAV antigen was performed in 47/81 individuals (21 with PAL, 26 with UAL) to identify activated CD4 + memory T cells or CD8 + memory T cells. The results showed that 48/52 (92%) individuals from UAL group who completed follow up reached protective levels after booster dose. In the PAL group, anti-HAV Abs waned in 2/27 (7%) individuals lacking seroprotection, while in 25/27 (93%) Abs remained >10 mUI/mL. HAV-specific memory CD4 + T cells were detected in 25/47 (53.2%) subjects while HAV-specific memory CD8 + T cells were observed in 16/47 (34.04%) individuals. HAV-specific memory CD4 and CD8 T cell responses were detected in 11/21 (52.4%) and in 9/21 (42.9%) subjects with PAL and in 14/26 (53.8%) and in 7/26 (26.9%) individuals with UAL, showing that the presence of memory T-cells was independent of the level or presence of anti-HAV antibodies. Long-term immunity demonstrated in the present work, including or not antibody persistence, suggests that individuals with waned Ab titers may still be protected and supports the single-dose HAV strategy.
婴儿甲型肝炎病毒（HAV）单剂量疫苗接种在阿根廷以及其他采用该策略的拉丁美洲国家，对于控制HAV感染已取得了显著成效。尽管抗体水平会随时间下降，但这并未引发HAV疫情或突破性感染，这表明记忆免疫发挥了重要作用。本研究评估了HAV单剂量疫苗接种平均12年随访后的长期体液免疫和细胞免疫记忆反应。我们从2015年的一项研究中选取了81名接种过HAV单剂量疫苗的个体，其中包括54名抗HAV抗体水平未达保护标准（UAL）的个体和27名抗HAV抗体水平达保护标准（PAL）的个体。通过测量两组个体入院时以及UAL组在加强剂量后30天的抗HAV抗体滴度，评估体液免疫记忆反应。对47/81名个体（21名PAL个体和26名UAL个体）的外周血单个核细胞样本进行HAV抗原刺激后的流式细胞术分析，以鉴定活化的CD4 +记忆T细胞或CD8 +记忆T细胞。结果显示，完成随访的UAL组中48/52（92%）的个体在加强剂量后达到了保护水平。在PAL组中，2/27（7%）缺乏血清保护的个体抗HAV抗体水平下降，而25/27（93%）的个体抗体水平仍>10 mUI/mL。在25/47（53.2%）的受试者中检测到了HAV特异性记忆CD4 + T细胞，在16/47（34.04%）的个体中观察到了HAV特异性记忆CD8 + T细胞。在PAL组的11/21（52.4%）和9/21（42.9%）受试者以及UAL组的14/26（53.8%）和7/26（26.9%）个体中检测到了HAV特异性记忆CD4和CD8 T细胞反应，这表明记忆T细胞的存在与抗HAV抗体水平或是否存在无关。本研究中所展示的长期免疫力，包括抗体是否持续存在，表明抗体滴度下降的个体仍可能受到保护，并支持HAV单剂量疫苗接种策略。
