Abstract：
BACKGROUND: A single dose of Ad26.COV2.S is well-tolerated and effective in preventing moderate-to-severe disease outcomes due to COVID-19. We evaluated the impact of dose level, number of doses, and dose interval on immunogenicity, reactogenicity, and safety of Ad26.COV2.S in adults. Anamnestic responses were also explored.
METHODS: This randomised, double-blind, placebo-controlled, Phase 2a study was conducted in adults aged 18-55 years and ≥ 65 years (NCT04535453). Four dose levels (1.25 × 1010, 2.5 × 1010, 5 × 1010, and 1 × 1011 viral particles [vp], single and 2-dose schedules, and dose intervals of 56 and 84 days, were assessed. Four or 6 months post-primary vaccination, Ad26.COV2.S 1.25 × 1010 vp was given to evaluate anamnestic responses. Humoral and cell-mediated immune responses were measured. Reactogenicity and safety were assessed in all participants.
RESULTS: All Ad26.COV2.S schedules induced humoral responses with evidence of a dose response relationship. A single dose of Ad26.COV2.S (5 × 1010 vp) induced antibody and cellular immune responses that persisted for up to at least 6 months. In the 2-dose regimens, antibody responses were higher than 1-dose regimens at comparable dose levels, and the magnitude of the immune response increased when the interval between doses was increased (84 days vs 56 days). Rapid, marked immune responses were observed in all groups after vaccine antigen exposure indicating immune memory. Durable immune responses were observed in all groups for up to at least 6 months post-antigen exposure. Strong and consistent correlations between neutralising and binding antibodies were observed CD4 + and CD8 + T cell responses were similar after all regimens. Reactogenicity within 7 days post-vaccination tended to be dose-related.
CONCLUSIONS: The study supports the primary, single dose schedule with Ad26.COV2.S at 5 × 1010 vp and homologous booster vaccination after a 6 month interval. Rapid and marked responses to vaccine antigen exposure indicate induction of immune memory by 1- and 2-dose primary vaccination.
METHODS: This randomised, double-blind, placebo-controlled, Phase 2a study was conducted in adults aged 18-55 years and ≥ 65 years (NCT04535453). Four dose levels (1.25 × 1010, 2.5 × 1010, 5 × 1010, and 1 × 1011 viral particles [vp], single and 2-dose schedules, and dose intervals of 56 and 84 days, were assessed. Four or 6 months post-primary vaccination, Ad26.COV2.S 1.25 × 1010 vp was given to evaluate anamnestic responses. Humoral and cell-mediated immune responses were measured. Reactogenicity and safety were assessed in all participants.
RESULTS: All Ad26.COV2.S schedules induced humoral responses with evidence of a dose response relationship. A single dose of Ad26.COV2.S (5 × 1010 vp) induced antibody and cellular immune responses that persisted for up to at least 6 months. In the 2-dose regimens, antibody responses were higher than 1-dose regimens at comparable dose levels, and the magnitude of the immune response increased when the interval between doses was increased (84 days vs 56 days). Rapid, marked immune responses were observed in all groups after vaccine antigen exposure indicating immune memory. Durable immune responses were observed in all groups for up to at least 6 months post-antigen exposure. Strong and consistent correlations between neutralising and binding antibodies were observed CD4 + and CD8 + T cell responses were similar after all regimens. Reactogenicity within 7 days post-vaccination tended to be dose-related.
CONCLUSIONS: The study supports the primary, single dose schedule with Ad26.COV2.S at 5 × 1010 vp and homologous booster vaccination after a 6 month interval. Rapid and marked responses to vaccine antigen exposure indicate induction of immune memory by 1- and 2-dose primary vaccination.
摘要：
背景：单剂量的Ad26。COV2.S耐受性良好，可有效预防COVID-19导致的中度至重度疾病结局。我们评估了剂量水平的影响，剂量的数量，和免疫原性的剂量间隔，反应原性,Ad26的安全性COV2.S在成人还探索了记忆障碍的反应。
方法：这是随机的，双盲,安慰剂对照,2a期研究在18-55岁和≥65岁的成年人中进行(NCT04535453)。四种剂量水平（1.25×1010，2.5×1010，5×1010和1×1011病毒颗粒[vp]，单剂量和2剂量时间表，和56天和84天的剂量间隔，被评估。初次疫苗接种后4或6个月，Ad26.COV2.S1.25×1010vp用于评估记忆反应。测量体液和细胞介导的免疫应答。对所有参与者进行反应性和安全性评估。
结果：全部Ad26。COV2.S时间表诱导体液反应，并有剂量反应关系的证据。单剂量的Ad26。COV2.S（5×1010vp）诱导的抗体和细胞免疫反应持续至少6个月。在2剂量方案中，在相当的剂量水平下，抗体反应高于1剂量方案，当剂量间隔增加时（84天对56天），免疫反应的幅度增加。快速，疫苗抗原暴露后，所有组均观察到明显的免疫反应，表明免疫记忆。在抗原暴露后至少6个月,在所有组中观察到持久的免疫应答。观察到中和抗体与结合抗体之间的强烈且一致的相关性,在所有方案之后,CD4+和CD8+T细胞应答是相似的。疫苗接种后7天内的反应原性倾向于剂量相关。
结论：该研究支持主要的，单剂量方案与Ad26。COV2.5×1010vp的S和6个月间隔后的同源加强疫苗接种。对疫苗抗原暴露的快速和显著的反应表明通过1-和2-剂量初次疫苗接种诱导免疫记忆。
方法：这是随机的，双盲,安慰剂对照,2a期研究在18-55岁和≥65岁的成年人中进行(NCT04535453)。四种剂量水平（1.25×1010，2.5×1010，5×1010和1×1011病毒颗粒[vp]，单剂量和2剂量时间表，和56天和84天的剂量间隔，被评估。初次疫苗接种后4或6个月，Ad26.COV2.S1.25×1010vp用于评估记忆反应。测量体液和细胞介导的免疫应答。对所有参与者进行反应性和安全性评估。
结果：全部Ad26。COV2.S时间表诱导体液反应，并有剂量反应关系的证据。单剂量的Ad26。COV2.S（5×1010vp）诱导的抗体和细胞免疫反应持续至少6个月。在2剂量方案中，在相当的剂量水平下，抗体反应高于1剂量方案，当剂量间隔增加时（84天对56天），免疫反应的幅度增加。快速，疫苗抗原暴露后，所有组均观察到明显的免疫反应，表明免疫记忆。在抗原暴露后至少6个月,在所有组中观察到持久的免疫应答。观察到中和抗体与结合抗体之间的强烈且一致的相关性,在所有方案之后,CD4+和CD8+T细胞应答是相似的。疫苗接种后7天内的反应原性倾向于剂量相关。
结论：该研究支持主要的，单剂量方案与Ad26。COV2.5×1010vp的S和6个月间隔后的同源加强疫苗接种。对疫苗抗原暴露的快速和显著的反应表明通过1-和2-剂量初次疫苗接种诱导免疫记忆。
