CD4/CD8 Ratio and KT Ratio Predict Yellow Fever Vaccine Immunogenicity in HIV-Infected Patients
CD4/CD8 Ratio and KT Ratio Predict Yellow Fever Vaccine Immunogenicity in HIV-Infected Patients
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DOI：
10.1371/journal.pntd.0005219
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发表时间：
2016-12-01
影响因子：
3.8
通讯作者：
Kallas, Esper G.
中科院分区：
文献类型：
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作者：
Avelino-Silva, Vivian I.;Miyaji, Karina T.;Kallas, Esper G.
研究背景HIV感染者对黄热病疫苗（YFV）的免疫应答不足，可能有更高的不良反应风险。慢性免疫激活的特点是低的CD 4/CD 8的比例或高吲哚胺2，3-双加氧酶-1（IDO）的活动D可能会影响疫苗的反应，在此population.MethodsWe前瞻性评估AE，病毒血症的YFV病毒和YF特异性中和抗体（NAB）在HIV感染（CD 4>350）和未感染的成人通过1年后接种。在接种疫苗后的前3个月内测量HIV状态对YFV初始抗体应答的影响，而在接种疫苗后1年测量对抗体应答持续性的影响。采用线性混合模型分析了HIV感染者的CD 4/CD 8比值、IDO活性（血浆犬尿氨酸/色氨酸[KT]比值）和病毒血症对NAb对YFV应答的预测作用。在接种后的前3个月内，HIV与AE、YFV病毒血症或NAb滴度无显著相关性。然而，在YFV后1年，HIV感染者的NAb滴度是HIV未感染者的0.32倍（95%CI 0.13至0.83，p = 0.021），与性别、年龄和既往接种无关。在HIV感染者中，CD 4/CD 8比值每增加10%，预测基线后YFV Nab滴度平均增加21%（p = 0.024）。同样，KT比值每增加10%，预测基线后YFV Nab滴度平均降低21%（p = 0.009）。人Pegivirus病毒血症与NAb滴度没有显着相关性。ConclusionsHIV感染似乎降低了NAb对YFV的反应的持久性，这种效应可以通过较低的CD 4/CD 8比率或较高的KT比率来预测。
BackgroundHIV-infected individuals have deficient responses to Yellow Fever vaccine (YFV) and may be at higher risk for adverse events (AE). Chronic immune activation-characterized by low CD4/CD8 ratio or high indoleamine 2,3-dioxygenase-1 (IDO) activity D may influence vaccine response in this population.MethodsWe prospectively assessed AE, viremia by the YFV virus and YF-specific neutralizing antibodies (NAb) in HIV-infected (CD4>350) and -uninfected adults through 1 year after vaccination. The effect of HIV status on initial antibody response to YFV was measured during the first 3 months following vaccination, while the effect on persistence of antibody response was measured one year following vaccination. We explored CD4/CD8 ratio, IDO activity (plasma kynurenine/tryptophan [KT] ratio) and viremia by Human Pegivirus as potential predictors of NAb response to YFV among HIV-infected participants with linear mixed models.Results12 HIV-infected and 45-uninfected participants were included in the final analysis. HIV was not significantly associated with AE, YFV viremia or NAb titers through the first 3 months following vaccination. However, HIV-infected participants had 0.32 times the NAb titers observed for HIV-uninfected participants at 1 year following YFV (95% CI 0.13 to 0.83, p = 0.021), independent of sex, age and prior vaccination. In HIV-infected participants, each 10% increase in CD4/CD8 ratio predicted a mean 21% higher post-baseline YFV Nab titer (p = 0.024). Similarly, each 10% increase in KT ratio predicted a mean 21% lower post-baseline YFV Nab titer (p = 0.009). Viremia by Human Pegivirus was not significantly associated with NAb titers.ConclusionsHIV infection appears to decrease the durability of NAb responses to YFV, an effect that may be predicted by lower CD4/CD8 ratio or higher KT ratio.