严重急性呼吸综合征冠状病毒2变体疫苗加强针试验：初步分析。
SARS-CoV-2 Variant Vaccine Boosters Trial: Preliminary Analyses.
作者信息
Branche Angela R, Rouphael Nadine G, Diemert David J, Falsey Ann R, Losada Cecilia, Baden Lindsey R, Frey Sharon E, Whitaker Jennifer A, Little Susan J, Anderson Evan J, Walter Emmanuel B, Novak Richard M, Rupp Richard, Jackson Lisa A, Babu Tara M, Kottkamp Angelica C, Luetkemeyer Anne F, Immergluck Lilly C, Presti Rachel M, Bäcker Martín, Winokur Patricia L, Mahgoub Siham M, Goepfert Paul A, Fusco Dahlene N, Malkin Elissa, Bethony Jeffrey M, Walsh Edward E, Graciaa Daniel S, Samaha Hady, Sherman Amy C, Walsh Stephen R, Abate Getahun, Oikonomopoulou Zacharoula, El Sahly Hana M, Martin Thomas C S, Rostad Christina A, Smith Michael J, Ladner Benjamin G, Porterfield Laura, Dunstan Maya, Wald Anna, Davis Tamia, Atmar Robert L, Mulligan Mark J, Lyke Kirsten E, Posavad Christine M, Meagher Megan A, Stephens David S, Neuzil Kathleen M, Abebe Kuleni, Hill Heather, Albert Jim, Lewis Teri C, Giebeig Lisa A, Eaton Amanda, Netzl Antonia, Wilks Samuel H, Türeli Sina, Makhene Mamodikoe, Crandon Sonja, Lee Marina, Nayak Seema U, Montefiori David C, Makowski Mat, Smith Derek J, Roberts Paul C, Beigel John H
出版信息
medRxiv. 2022 Jul 15:2022.07.12.22277336. doi: 10.1101/2022.07.12.22277336.
BACKGROUND
Protection from SARS-CoV-2 vaccines wanes over time and is compounded by emerging variants including Omicron subvariants. This study evaluated safety and immunogenicity of SARS-CoV-2 variant vaccines.
METHODS
This phase 2 open-label, randomized trial enrolled healthy adults previously vaccinated with a SARS-CoV-2 primary series and a single boost. Eligible participants were randomized to one of six Moderna COVID19 mRNA vaccine arms (50µg dose): Prototype (mRNA-1273), Omicron BA.1+Beta (1 or 2 doses), Omicron BA.1+Delta, Omicron BA.1 monovalent, and Omicron BA.1+Prototype. Neutralization antibody titers (ID ) were assessed for D614G, Delta, Beta and Omicron BA.1 variants and Omicron BA.2.12.1 and BA.4/BA.5 subvariants 15 days after vaccination.
RESULTS
From March 30 to May 6, 2022, 597 participants were randomized and vaccinated. Median age was 53 years, and 20% had a prior SARS-CoV-2 infection. All vaccines were safe and well-tolerated. Day 15 geometric mean titers (GMT) against D614G were similar across arms and ages, and higher with prior infection. For uninfected participants, Day 15 Omicron BA.1 GMTs were similar across Omicron-containing vaccine arms (3724-4561) and higher than Prototype (1,997 [95%CI:1,482-2,692]). The Omicron BA.1 monovalent and Omicron BA.1+Prototype vaccines induced a geometric mean ratio (GMR) to Prototype for Omicron BA.1 of 2.03 (97.5%CI:1.37-3.00) and 1.56 (97.5%CI:1.06-2.31), respectively. A subset of samples from uninfected participants in four arms were also tested in a different laboratory at Day 15 for neutralizing antibody titers to D614G and Omicron subvariants BA.1, BA.2.12.2 and BA.4/BA.5. Omicron BA.4/BA.5 GMTs were approximately one third BA.1 GMTs (Prototype 517 [95%CI:324-826] vs. 1503 [95%CI:949-2381]; Omicron BA.1+Beta 628 [95%CI:367-1,074] vs. 2125 [95%CI:1139-3965]; Omicron BA.1+Delta 765 [95%CI:443-1,322] vs. 2242 [95%CI:1218-4128] and Omicron BA.1+Prototype 635 [95%CI:447-903] vs. 1972 [95%CI:1337-2907).
CONCLUSIONS
Higher Omicron BA.1 titers were observed with Omicron-containing vaccines compared to Prototype vaccine and titers against Omicron BA.4/BA.5 were lower than against BA.1 for all candidate vaccines.
CLINICALTRIALSGOV
NCT05289037.
背景
新冠病毒疫苗的保护作用会随着时间减弱，且包括奥密克戎亚变体在内的新变种使情况更加复杂。本研究评估了新冠病毒变种疫苗的安全性和免疫原性。
方法
这项2期开放标签随机试验招募了先前接种过新冠病毒初级系列疫苗和一剂加强针的健康成年人。符合条件的参与者被随机分配到六种莫德纳新冠mRNA疫苗组之一（50µg剂量）：原型株（mRNA-1273）、奥密克戎BA.1+贝塔株（1或2剂）、奥密克戎BA.1+德尔塔株、奥密克戎BA.1单价株和奥密克戎BA.1+原型株。在接种疫苗15天后，评估针对D614G、德尔塔、贝塔和奥密克戎BA.1变种以及奥密克戎BA.2.12.1和BA.4/BA.5亚变体的中和抗体滴度（ID ）。
结果
2022年3月30日至5月6日，597名参与者被随机分组并接种疫苗。中位年龄为53岁，20%的人曾感染过新冠病毒。所有疫苗均安全且耐受性良好。各疫苗组和各年龄组针对D614G的第15天几何平均滴度（GMT）相似，既往感染过的参与者GMT更高。对于未感染的参与者，含奥密克戎疫苗组的第15天奥密克戎BA.1 GMT相似（3724 - 4561），且高于原型株组（1997 [95%CI：1482 - 2692]）。奥密克戎BA.1单价株疫苗和奥密克戎BA.1+原型株疫苗针对奥密克戎BA.1的几何平均比值（GMR）分别为2.03（97.5%CI：1.37 - 3.00）和1.56（97.5%CI：1.06 - 2.31）。来自四个疫苗组未感染参与者的一部分样本在第15天还在另一个实验室进行了检测，以测定针对D614G和奥密克戎亚变体BA.1、BA.2.12.2和BA.4/BA.5的中和抗体滴度。奥密克戎BA.4/BA.5的GMT约为BA.1 GMT的三分之一（原型株组：517 [95%CI：324 - 826] 对比1503 [95%CI：949 - 2381]；奥密克戎BA.1+贝塔株组：628 [95%CI：367 - 1074] 对比2125 [95%CI：1139 - 3965]；奥密克戎BA.1+德尔塔株组：765 [95%CI：443 - 1322] 对比2242 [95%CI：1218 - 4128]；奥密克戎BA.1+原型株组：635 [95%CI：447 - 903] 对比1972 [95%CI：1337 - 2907]）。
结论
与原型株疫苗相比，含奥密克戎疫苗的奥密克戎BA.1滴度更高，且所有候选疫苗针对奥密克戎BA.4/BA.5的滴度低于针对BA.1的滴度。
临床试验注册号
NCT05289037。
Zotero 插件