Vaccine Clinical Research, Pfizer Inc, Sydney, Australia.
Australian Clinical Research Network, Maroubra, Australia.
J Infect Dis. 2022 Dec 13;226(12):2054-2063. doi: 10.1093/infdis/jiac189.
Respiratory syncytial virus (RSV) is an important cause of disease in older adults. We evaluated the safety and immunogenicity of a stabilized RSV prefusion F subunit (RSVpreF) vaccine candidate with/without adjuvant in adults aged 65-85 years.
Primary cohort participants were equally randomized to 1 of 7 RSVpreF formulations: 60 µg with either Al(OH)3 or CpG/Al(OH)3, 120 µg with either Al(OH)3 or CpG/Al(OH)3, 240 µg with either Al(OH)3 or CpG/Al(OH)3, 240 µg unadjuvanted, or placebo, administered concomitantly with high-dose seasonal inactivated influenza vaccine (SIIV). Participants in the month 0,2 cohort were randomized to RSVpreF 240 µg with CpG/Al(OH)3 or placebo, administered at months 0 and 2.
All RSVpreF vaccine candidates elicited robust and persistent serum neutralizing responses when administered alone or with SIIV. There was no notable difference in neutralizing response between the formulations, including those containing CpG. In the month 0,2 cohort, there was no booster effect of dose 2. SIIV responses were similar or slightly lower with concomitant administration of RSVpreF. Most systemic and local reactions were mild and more frequent after RSVpreF than placebo.
RSVpreF formulations were well tolerated and elicited robust neutralizing responses in older adults; however, CpG/Al(OH)3 did not further enhance responses. Clinical Trials Registration. NCT03572062.
呼吸道合胞病毒(RSV)是老年人发病的重要原因。我们评估了一种带有/不带有佐剂的稳定 RSV 融合前 F 亚单位(RSVpreF)候选疫苗在 65-85 岁成年人中的安全性和免疫原性。
主要队列参与者被平均随机分为 7 种 RSVpreF 制剂中的 1 种:60μg 与 Al(OH)3 或 CpG/Al(OH)3 联合使用、120μg 与 Al(OH)3 或 CpG/Al(OH)3 联合使用、240μg 与 Al(OH)3 或 CpG/Al(OH)3 联合使用、240μg 未添加佐剂或安慰剂,同时接种高剂量季节性流感疫苗(SIIV)。0、2 月队列的参与者被随机分为 RSVpreF 240μg 与 CpG/Al(OH)3 或安慰剂,在 0 月和 2 月接种。
当单独或与 SIIV 联合使用时,所有 RSVpreF 候选疫苗均能引起强烈且持久的血清中和反应。制剂之间的中和反应没有明显差异,包括含有 CpG 的制剂。在 0、2 月队列中,第 2 剂没有增强作用。同时使用 RSVpreF 可使 SIIV 反应相似或略低。大多数全身和局部反应较轻,接种 RSVpreF 后比安慰剂更频繁。
RSVpreF 制剂在老年人中耐受性良好,并引起强烈的中和反应;然而,CpG/Al(OH)3 并没有进一步增强反应。临床试验注册。NCT03572062。