Low-dose Ad26.COV2.S protection against SARS-CoV-2 challenge in rhesus macaques.
Low-dose Ad26.COV2.S protection against SARS-CoV-2 challenge in rhesus macaques.
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DOI：
10.1016/j.cell.2021.05.040
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发表时间：
2021-06-24
期刊：
影响因子：
64.5
通讯作者：
Barouch DH
中科院分区：
文献类型：
--
作者：
He X;Chandrashekar A;Zahn R;Wegmann F;Yu J;Mercado NB;McMahan K;Martinot AJ;Piedra-Mora C;Beecy S;Ducat S;Chamanza R;Huber SR;van Heerden M;van der Fits L;Borducchi EN;Lifton M;Liu J;Nampanya F;Patel S;Peter L;Tostanoski LH;Pessaint L;Van Ry A;Finneyfrock B;Velasco J;Teow E;Brown R;Cook A;Andersen H;Lewis MG;Schuitemaker H;Barouch DH
我们先前报道了用表达优化的SARS-CoV-2刺突的基于腺病毒血清型26（Ad 26）载体的疫苗（Ad26.COV2.S）单次免疫保护恒河猴对抗SARS-CoV-2攻击。为了评估减少剂量的Ad26.COV2.S，用1 × 1011、5 × 1010、1.125 × 1010或2 × 109病毒颗粒（vp）Ad26.COV2.S或假疫苗免疫30只恒河猴一次，并用SARS-CoV-2攻击。低至2 × 109 vp的疫苗剂量在支气管肺泡灌洗中提供了稳健的保护，而鼻拭子中的保护需要1.125 × 1010 vp的剂量。免疫后激活的记忆B细胞和结合或中和抗体滴度与保护效力相关。在次优疫苗剂量下，观察到病毒突破，但未显示疾病增强。这些数据表明，用相对低剂量的Ad26.COV2.S单次免疫可有效保护恒河猴免受SARS-CoV-2攻击，尽管可能需要更高的疫苗剂量来保护上呼吸道。对减少剂量的单次注射Ad26.COV2.S的评估揭示了对SARS-CoV-2攻击的保护，而没有增强疾病。可能需要更高的剂量来保护上呼吸道。
We previously reported that a single immunization with an adenovirus serotype 26 (Ad26)-vector-based vaccine expressing an optimized SARS-CoV-2 spike (Ad26.COV2.S) protected rhesus macaques against SARS-CoV-2 challenge. To evaluate reduced doses of Ad26.COV2.S, 30 rhesus macaques were immunized once with 1 × 1011, 5 × 1010, 1.125 × 1010, or 2 × 109 viral particles (vp) Ad26.COV2.S or sham and were challenged with SARS-CoV-2. Vaccine doses as low as 2 × 109 vp provided robust protection in bronchoalveolar lavage, whereas doses of 1.125 × 1010 vp were required for protection in nasal swabs. Activated memory B cells and binding or neutralizing antibody titers following vaccination correlated with protective efficacy. At suboptimal vaccine doses, viral breakthrough was observed but did not show enhancement of disease. These data demonstrate that a single immunization with relatively low dose of Ad26.COV2.S effectively protected against SARS-CoV-2 challenge in rhesus macaques, although a higher vaccine dose may be required for protection in the upper respiratory tract. Evaluation of a reduced dosage of the single-shot Ad26.COV2.S reveals protection against SARS-CoV-2 challenge without enhancement of disease. A higher dosage may be needed for protection in the upper respiratory tract.
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