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mRNA 疫苗第五剂加强针接种后对 HIV 感染者中和抗体活性和 T 细胞应答的影响。

Neutralizing activity and T-cell response after bivalent fifth dose of messenger RNA vaccine in people living with HIV.

机构信息

National Institute for Infectious Diseases Lazzaro Spallanzani, Scientific Hospital and Care Institutions, HIV/AIDS Unit, Rome, Italy.

National Institute for Infectious Diseases Lazzaro Spallanzani, Scientific Hospital and Care Institutions, Laboratory of Virology, Rome, Italy.

出版信息

Int J Infect Dis. 2023 Sep;134:195-199. doi: 10.1016/j.ijid.2023.06.010. Epub 2023 Jun 19.

Abstract

OBJECTIVES

To investigate immunogenicity of SARS-CoV-2 vaccine third booster dose (3BD; fifth dose) with bivalent vaccine original/BA4/5 vaccine in people living with HIV (PLWH).

METHODS

This is an observational cohort study to evaluate the outcomes of SARS-CoV-2 vaccination (HIV-VAC study). We analyzed microneutralization assay and interferon-γ production in 48 PLWH on antiretroviral therapy with clusters of differentiation (CD4) count <200 cell/mm and/or previous AIDS according to immunization status: vaccinated PLWH who had a previous SARS-CoV-2 infection (hybrid immunization, HI) vs those only vaccinated (non-hybrid immunization, nHI) and current CD4 count.

RESULTS

After 15 days from its administration (T1), the 3BD bivalent messenger RNA vaccine elicited a statistically significant increase of neutralizing antibodies (nAbs) geometric mean titers from T0 to T1 against W-D614G (fold increase 4.8; P <0.0001), BA.5 (8.6 P <0.0001), BQ.1.1 (6.4, P <0.0001) and XBB.1 (6.5, P <0.0001). When compared to BA.5, nAbs geometric mean titers against BQ.1.1 and XBB.1 decreased by 3.5 and 4.1-fold, respectively. After controlling for age, years from AIDS diagnosis, CD4 count at administration and CD4 count nadir, the fold change reduction in nAbs response to other variants of concerns as compared to BA.1, was larger in participants with HI vs those nHI: 0.59 lower (95% confidence interval 0.36-0.97, P = 0.04) for BQ.1.1 and 0.67 lower (95% confidence interval: 0.47-0.96, P = 0.03) for XBB.1. In contrast, the analysis carried little evidence for an association between current CD4 count and response to the fifth dose of bivalent vaccine. Furthermore, cell-mediated immunity remained stable.

CONCLUSION

Our data support the current recommendation of offering bivalent mRNA vaccine booster doses to PLWH with low CD4 count or previous AIDS at first vaccination, especially in those who never previously acquired SARS-CoV-2 and regardless of current CD4 count.

摘要

目的

研究在接受抗逆转录病毒治疗且 CD4 计数<200 个细胞/mm3或既往有艾滋病的 HIV 感染者(PLWH)中,使用二价疫苗原始株/BA4/5 疫苗进行 SARS-CoV-2 疫苗第三剂加强接种(3BD;第五剂)的免疫原性。

方法

这是一项观察性队列研究,旨在评估 SARS-CoV-2 疫苗接种(HIV-VAC 研究)的结果。我们分析了 48 名接受抗逆转录病毒治疗且 CD4 计数<200 个细胞/mm3或既往有艾滋病的 PLWH 中的微中和试验和干扰素-γ产生情况,这些患者根据免疫接种状态分为以下两组:既往 SARS-CoV-2 感染(混合免疫,HI)的接种 PLWH 与仅接种疫苗(非混合免疫,nHI)的 PLWH,以及当前的 CD4 计数。

结果

在接种后 15 天(T1),3BD 二价信使 RNA 疫苗接种引起了针对 W-D614G(倍数增加 4.8;P<0.0001)、BA.5(8.6 P<0.0001)、BQ.1.1(6.4,P<0.0001)和 XBB.1(6.5,P<0.0001)的中和抗体(nAbs)几何平均滴度从 T0 到 T1 的统计学显著增加。与 BA.5 相比,BQ.1.1 和 XBB.1 的 nAbs 几何平均滴度分别降低了 3.5 倍和 4.1 倍。在控制年龄、从艾滋病诊断到接种疫苗的时间、接种疫苗时的 CD4 计数和 CD4 计数最低点后,与 BA.1 相比,HI 组与 nHI 组相比,对其他关注变异体的 nAbs 反应降低的倍数变化更大:BQ.1.1 降低 0.59(95%置信区间 0.36-0.97,P=0.04),XBB.1.1 降低 0.67(95%置信区间:0.47-0.96,P=0.03)。相比之下,分析结果几乎没有证据表明当前 CD4 计数与二价疫苗第五剂接种后的反应之间存在关联。此外,细胞介导的免疫保持稳定。

结论

我们的数据支持目前的建议,即对首次接种时 CD4 计数较低或既往有艾滋病的 PLWH 提供二价 mRNA 疫苗加强接种,尤其是对从未感染过 SARS-CoV-2 且无论当前 CD4 计数如何的 PLWH 提供加强接种。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d63e/10277256/02e76b290ac8/gr1_lrg.jpg

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