Safety and immunogenicity of the RTS,S/AS01 malaria vaccine in infants and children identified as HIV-infected during a randomized trial in sub-Saharan Africa.
Safety and immunogenicity of the RTS,S/AS01 malaria vaccine in infants and children identified as HIV-infected during a randomized trial in sub-Saharan Africa.
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DOI：
10.1016/j.vaccine.2019.10.077
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发表时间：
2020-01-22
期刊：
影响因子：
5.5
通讯作者：
Oneko M
中科院分区：
文献类型：
--
作者：
Otieno L;Guerra Mendoza Y;Adjei S;Agbenyega T;Agnandji ST;Aide P;Akoo P;Ansong D;Asante KP;Berkley JA;Gesase S;Hamel MJ;Hoffman I;Kaali S;Kamthunzi P;Kariuki S;Kremsner P;Lanaspa M;Lell B;Lievens M;Lusingu J;Malabeja A;Masoud NS;Mtoro AT;Njuguna P;Ofori-Anyinam O;Otieno GA;Otieno W;Owusu-Agyei S;Schuerman L;Sorgho H;Tanner M;Tinto H;Valea I;Vandoolaeghe P;Sacarlal J;Oneko M
我们在7个撒哈拉以南非洲国家进行了一项大型III期随机对照试验，评估了RTS、S/AS01疟疾疫苗在被确认为艾滋病毒感染的儿童子集中的安全性和免疫原性。在研究的0、1、2、20个月，6~12周的婴儿和5~17个月的儿童随机接受4剂RT、S/AS01剂(R3R组)、3剂RTS、S/AS01剂加1剂对照疫苗(R3C组)或4剂对照疫苗(C3C组)。排除了患有WHO III/IV期HIV疾病的婴儿和儿童，但不对所有参与者进行常规的HIV检测；我们的分析包括根据病史或临床怀疑并经聚合酶链式反应或抗体检测证实为HIV感染的儿童。评估严重不良事件(SAE)和抗环子孢子(CS)抗体。在参加试验的15459名儿童中，至少有1,953人接受了艾滋病毒检测，153人被确认为艾滋病毒感染者(R3R：51；R3C：54；C3C：48)。在这些儿童中，R3R组、R3C组和C3C组的SAE发生率分别为92.2%(95%CI：81.1-97.8)、85.2%(72.9-93.4)和87.5%(74.8-95.3)，中位随访期分别为39.3、39.4和38.3个月。每组中有15名艾滋病毒感染者在研究期间死亡(R3R：29.4%，R3C：27.8%，C3C：31.3%)。没有死亡被认为与疫苗接种有关。在配对病例对照分析中，接种后1个月抗CS几何平均抗体浓度在接种后1个月分别为193.3 EU/m L、491.5 EU/m L和491.5 EU/m L(P=0.0001)。在HIV感染的儿童中，RTS、S/AS01的安全性与对照疫苗(脑膜炎双球菌或狂犬病)相当。RT-S、S/AS01在HIV感染的儿童中具有免疫原性，但抗体浓度低于HIV状态未知或阴性的儿童。
We assessed the safety and immunogenicity of the RTS,S/AS01 malaria vaccine in a subset of children identified as HIV-infected during a large phase III randomized controlled trial conducted in seven sub-Saharan African countries. Infants 6–12 weeks and children 5–17 months old were randomized to receive 4 RTS,S/AS01 doses (R3R group), 3 RTS,S/AS01 doses plus 1 comparator vaccine dose (R3C group), or 4 comparator vaccine doses (C3C group) at study months 0, 1, 2 and 20. Infants and children with WHO stage III/IV HIV disease were excluded but HIV testing was not routinely performed on all participants; our analyses included children identified as HIV-infected based on medical history or clinical suspicion and confirmed by polymerase chain reaction or antibody testing. Serious adverse events (SAEs) and anti-circumsporozoite (CS) antibodies were assessed. Of 15459 children enrolled in the trial, at least 1953 were tested for HIV and 153 were confirmed as HIV-infected (R3R: 51; R3C: 54; C3C: 48). Among these children, SAEs were reported for 92.2% (95% CI: 81.1–97.8) in the R3R, 85.2% (72.9–93.4) in the R3C and 87.5% (74.8–95.3) in the C3C group over a median follow-up of 39.3, 39.4 and 38.3 months, respectively. Fifteen HIV-infected participants in each group (R3R: 29.4%, R3C: 27.8%, C3C: 31.3%) died during the study. No deaths were considered vaccination-related. In a matched case-control analysis, 1 month post dose 3 anti-CS geometric mean antibody concentrations were 193.3 EU/mL in RTS,S/AS01-vaccinated HIV-infected children and 491.5 EU/mL in RTS,S/ AS01-vaccinated immunogenicity controls with unknown or negative HIV status (p = 0.0001). The safety profile of RTS,S/AS01 in HIV-infected children was comparable to that of the comparator (meningococcal or rabies) vaccines. RTS,S/AS01 was immunogenic in HIV-infected children but antibody concentrations were lower than in children with an unknown or negative HIV status.
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