Durability of ChAdOx1 nCoV-19 (AZD1222) vaccine and hybrid humoral immunity against variants including omicron BA.1 and BA.4 6 months after vaccination (COV005): a post-hoc analysis of a randomised, phase 1b-2a trial.
Durability of ChAdOx1 nCoV-19 (AZD1222) vaccine and hybrid humoral immunity against variants including omicron BA.1 and BA.4 6 months after vaccination (COV005): a post-hoc analysis of a randomised, phase 1b-2a trial.
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DOI：
10.1016/s1473-3099(22)00596-5
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发表时间：
2023-03
影响因子：
56.3
通讯作者：
Izu, Alane
中科院分区：
文献类型：
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作者：
Madhi, Shabir A.;Kwatra, Gaurav;Richardson, Simone, I;Koen, Anthonet L.;Baillie, Vicky;Cutland, Clare L.;Fairlie, Lee;Padayachee, Sherman D.;Dheda, Keertan;Barnabas, Shaun L.;Bhorat, Qasim Ebrahim;Briner, Carmen;Ahmed, Khatija;Aley, Parvinder K.;Bhikha, Sutika;Bhorat, A. E.;Esmail, Aliasgar;Horne, Elizea;Kaldine, Haajira;Mukendi, Christian K.;Madzorera, Vimbai Sharon;Manamela, Nelia P.;Masilela, Mduduzi;Hermanus, S. Tandile;Motlou, Thopisang;Mzindle, Nonkululeko;Oelofse, Suzette;Patel, Faeezah;Rhead, Sarah;Rossouw, Lindie;Taoushanis, Carol;van Eck, Samuel;Lambe, Teresa;Gilbert, Sarah C.;Pollard, Andrew J.;Moore, Penny L.;Izu, Alane
COVID-19疫苗在非洲的推广滞后，那里的SARS-CoV-2感染率很高。我们的目的是评估在接种ChAdOx-nCoV 19（AZD 1222）疫苗之前SARS-CoV-2感染对抗体应答的影响，直至180天。我们在南非的7个地点进行了一项随机、安慰剂对照、1b-2a期研究，在AZD 1222首次和第二次给药后进行了一项非设盲的事后免疫原性分析。使用血清抗核衣壳（抗N）免疫球蛋白G（IgG）电致发光免疫测定法将未感染HIV的AZD 1222受体分为基线血清阳性组或血清阴性组，以在AZD 1222首次给药前确定SARS-CoV-2感染。在第一次给药（第0天）、第二次给药（第28天）、第42天和第180天前测量IgG与加标物（抗S）和受体结合结构域（抗RBD）的结合。通过假病毒试验（第28天、第42天和第180天）测量针对SARS-CoV-2变体D 614 G、β、δ、γ和A.VOI.V2以及omicron BA 1和BA.4变体的中和抗体（NAb）。本试验已在ClinicalTrials.gov（NCT 04444674）和泛非临床试验注册中心（PACTR 202006922165132）注册。在185名随机分配至AZD 1222组的受试者中，我们在最终分析中纳入了91名基线血清学阳性受试者和58名基线血清学阴性受试者。在血清阳性组中，与第28天相比，第42天的抗S IgG（和抗RBD IgG）或中和抗体（NAb）滴度变化不大。血清阳性组的抗S（和抗RBD）IgG几何平均浓度（GMC）始终高于血清阴性组，包括第180天（GMC 517·8 [95% CI 411·3-651·9] vs 82·1 [55·2-122·3] BAU/mL）。此外，血清阳性组的D 614 G NAb几何平均滴度（GMT）高于血清阴性组，滴度至少为185（针对野生型α COVID-19的80%推定风险降低阈值[PRRT]）的百分比也高于血清阴性组，包括第180天（92.0%[74.0 - 99.0] vs 18.2%[2.3 - 51.8]）。在β、A.VOI.V2和γ中观察到类似结果。对于δ、BA.1和BA.4，在第28天和第42天，血清阳性组的NAb GMT和滴度高于PRRT的比例显著高于血清阴性组，但到第180天，两组之间不再存在差异。在非洲普通人群中，单剂量AZD 1222可以提高SARS-CoV-2抗体应答的幅度和质量，因为非洲普通人群的COVID-19疫苗覆盖率较低，SARS-CoV-2血清阳性率为90%。比尔和梅琳达·盖茨基金会、南非医学研究理事会、英国研究与创新、英国国家健康研究所和南非医学研究理事会。摘要的祖鲁语翻译见补充材料部分。
COVID-19 vaccine rollout is lagging in Africa, where there has been a high rate of SARS-CoV-2 infection. We aimed to evaluate the effect of SARS-CoV-2 infection before vaccination with the ChAdOx-nCoV19 (AZD1222) vaccine on antibody responses through to 180 days. We did an unmasked post-hoc immunogenicity analysis after the first and second doses of AZD1222 in a randomised, placebo-controlled, phase 1b–2a study done in seven locations in South Africa. AZD1222 recipients who were HIV-uninfected, were stratified into baseline seropositive or seronegative groups using the serum anti-nucleocapsid (anti-N) immunoglobulin G (IgG) electroluminescence immunoassay to establish SARS-CoV-2 infection before the first dose of AZD1222. Binding IgG to spike (anti-S) and receptor binding domain (anti-RBD) were measured before the first dose (day 0), second dose (day 28), day 42, and day 180. Neutralising antibody (NAb) against SARS-CoV-2 variants D614G, beta, delta, gamma, and A.VOI.V2, and omicron BA1 and BA.4 variants, were measured by pseudovirus assay (day 28, day 42, and day 180). This trial is registered with ClinicalTrials.gov, NCT04444674, and the Pan African Clinicals Trials Registry, PACTR202006922165132. Of 185 individuals who were randomly assigned to AZD1222, we included 91 individuals who were baseline seropositive and 58 who were baseline seronegative, in the final analysis. In the seropositive group, there was little change of anti-S IgG (and anti-RBD IgG) or neutralising antibody (NAb) titres at day 42 compared with at day 28. Anti-S (and anti-RBD) IgG geometric mean concentrations (GMCs) were higher throughout in the seropositive compared with the seronegative group, including at day 180 (GMCs 517·8 [95% CI 411·3–651·9] vs 82·1 [55·2–122·3] BAU/mL). Also D614G NAb geometric mean titres (GMTs) were higher in the seropositive group than the seronegative group, as was the percentage with titres of at least 185 (80% putative risk reduction threshold [PRRT] against wild-type–alpha COVID-19), including at day 180 (92·0% [74·0–99·0] vs 18·2% [2·3–51·8). Similar findings were observed for beta, A.VOI.V2, and gamma. For delta, BA.1, and BA.4, NAb GMTs and the proportion with titres above the PRRT were substantially higher in the seropositive compared with seronegative group at day 28 and day 42, but no longer differed between the groups by day 180. A single dose of AZD1222 in the general African population, where COVID-19 vaccine coverage is low and SARS-CoV-2 seropositivity is 90%, could enhance the magnitude and quality of antibody responses to SARS-CoV-2. The Bill & Melinda Gates Foundation, the South African Medical Research Council, the UK Research and Innovation, the UK National Institute for Health Research, and the South African Medical Research Council. For the Zulu translation of the abstract see Supplementary Materials section.