AstraZeneca COVID-19 vaccine induces robust broadly cross-reactive antibody responses in Malawian adults previously infected with SARS-CoV-2.

AstraZeneca COVID-19 vaccine induces robust broadly cross-reactive antibody responses in Malawian adults previously infected with SARS-CoV-2.
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阿斯利康COVID-19疫苗在先前感染SARS-CoV-2的马拉维成年人中诱导了强大的广泛交叉反应性抗体应答。

DOI:
10.1186/s12916-022-02342-z
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发表时间:
2022-03-28
期刊:
影响因子:
9.3
通讯作者:
Jambo KC
Jambo KC
中科院分区:
医学1区
文献类型:
--
作者:
Chibwana MG;Moyo-Gwete T;Kwatra G;Mandolo J;Hermanaus T;Motlou T;Mzindle N;Ayres F;Chaponda M;Tembo G;Mwenechanya P;Mitole N;Jassi C;Kamng'ona R;Afran L;Mzinza D;Mwandumba HC;Gordon SB;Jere K;Madhi S;Moore PL;Heyderman RS;Jambo KC

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结合和中和抗刺抗体在对抗SARS-CoV-2感染的免疫防御中起着关键作用。由于已知抗体会随着时间的推移而减弱,新的免疫逃避变体正在出现,我们的目标是评估既往感染过SARS-CoV-2的非洲成年人中抗Spike抗体的动态变化,并确定随后接种新冠肺炎疫苗的效果。采用前瞻性队列设计,我们在马拉维的布兰太尔招募了有实验室确认的轻/中度新冠肺炎的成年人,并对他们进行了270 天的随访(n = 52)。其中一部分人随后接受了单剂阿斯利康新冠肺炎疫苗(ChAdOx NCoV-19)(n = 12)。我们使用基于Luminex的分析方法测量了血清中抗Spike和受体结合域(RBD)抗体的浓度。用血凝试验检测SARS-CoV-2变异株(VOC)间抗RBD抗体的交叉反应性。假病毒中和试验被用来测量挥发性有机化合物的中和滴度。使用普通或重复测量的单因素方差分析比较log10变换后的数据,并使用Šídák或Holm-Šídák检验调整p值以进行多次比较。我们发现,在轻/中度感染SARS-CoV-2后的6个 月内,中和抗体减弱(30-60 天vs.210-270 天;LOGID50 6.8 vs.5.3,p = 0.0093)。恢复期血清中高水平的结合抗刺突或抗RBD抗体与对同源感染株的强大中和活性相关(p < 0.0001)。在轻/中度感染SARS-CoV-2后单剂注射阿斯利康新冠肺炎疫苗,可使接种后30 天的抗峰值抗体和RBDIg G水平增加2至3倍(p < 0.0001)。来自这些接种个体的抗RBD抗体对多种VOCs具有广泛的交叉反应,并对原始D614G、Beta和Delta变体具有中和效力。这些发现表明,阿斯利康新冠肺炎疫苗是一种有效的增强剂,可以有效地增强最初接种SARS-CoV-2感染后交叉变异抗体的免疫力。在撒哈拉以南非洲制定疫苗接种政策时,需要考虑到混合免疫的效力及其最大限度地发挥新冠肺炎疫苗效益的潜力,因为那里获得疫苗剂量的机会仍然有限。
Binding and neutralising anti-Spike antibodies play a key role in immune defence against SARS-CoV-2 infection. Since it is known that antibodies wane with time and new immune-evasive variants are emerging, we aimed to assess the dynamics of anti-Spike antibodies in an African adult population with prior SARS-CoV-2 infection and to determine the effect of subsequent COVID-19 vaccination. Using a prospective cohort design, we recruited adults with prior laboratory-confirmed mild/moderate COVID-19 in Blantyre, Malawi, and followed them up for 270 days (n = 52). A subset of whom subsequently received a single dose of the AstraZeneca COVID-19 vaccine (ChAdOx nCov-19) (n = 12). We measured the serum concentrations of anti-Spike and receptor-binding domain (RBD) IgG antibodies using a Luminex-based assay. Anti-RBD antibody cross-reactivity across SARS-CoV-2 variants of concern (VOC) was measured using a haemagglutination test. A pseudovirus neutralisation assay was used to measure neutralisation titres across VOCs. Ordinary or repeated measures one-way ANOVA was used to compare log10 transformed data, with p value adjusted for multiple comparison using Šídák's or Holm-Šídák's test. We show that neutralising antibodies wane within 6 months post mild/moderate SARS-CoV-2 infection (30–60 days vs. 210–270 days; Log ID50 6.8 vs. 5.3, p = 0.0093). High levels of binding anti-Spike or anti-RBD antibodies in convalescent serum were associated with potent neutralisation activity against the homologous infecting strain (p < 0.0001). A single dose of the AstraZeneca COVID-19 vaccine following mild/moderate SARS-CoV-2 infection induced a 2 to 3-fold increase in anti-Spike and -RBD IgG levels 30 days post-vaccination (both, p < 0.0001). The anti-RBD IgG antibodies from these vaccinated individuals were broadly cross-reactive against multiple VOCs and had neutralisation potency against original D614G, beta, and delta variants. These findings show that the AstraZeneca COVID-19 vaccine is an effective booster for waning cross-variant antibody immunity after initial priming with SARS-CoV-2 infection. The potency of hybrid immunity and its potential to maximise the benefits of COVID-19 vaccines needs to be taken into consideration when formulating vaccination policies in sub-Saharan Africa, where there is still limited access to vaccine doses.
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