Anselm Jorda, Marlene Prager, Lena Pracher, Patrick Haselwanter, Matthias Jackwerth, Valentin Al Jalali, Erdem Yildiz, Amelie Leutzendorff, Maria Weber, Schermin Yourieva, Paula Kammerer, Theresa Pecho, Alice Decaminada, Lena Ederer, Ursula Wiedermann, Lukas Weseslindtner, Monika Redlberger-Fritz, Felix Bergmann, Markus Zeitlinger
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引用次数: 0
摘要
目的：关于联合接种两种疫苗是否会导致较差的免疫原性和反应原性，目前存在相互矛盾的证据。此前尚未对 Novavax 公司生产的 Omicron 适应型 COVID-19 疫苗（NVX-CoV2601）和 20 价肺炎球菌结合疫苗（PCV20）的联合接种进行过研究：在这项随机、双盲、安慰剂对照、非劣效性试验中，年龄≥60岁的免疫功能正常者按1:1:1:1的比例被随机分为四组：NVX-CoV2601加PCV20（联合组）；NVX-CoV2601加安慰剂（仅NVX组）；PCV20加安慰剂（仅PCV20组）；或安慰剂加安慰剂（安慰剂组）。主要结果是，与纯 NVX 组相比，联合组在第 28 天时的 Omicron 特异性抗尖头蛋白 IgG ELISA 单位。如果几何平均滴度比的双侧 95% CI 的下限高于 0.67 的非劣效边际，则确定为非劣效性。次要结果包括抗肺炎球菌球囊多糖（PCP）IgG ELISA 单位。疫苗接种后 7 天内收集了局部和全身不良反应。该研究已在 ClinicalTrials.gov 注册，注册号为 NCT05767606，并在欧盟临床试验注册中心注册，注册号为 EudraCT 2022-004118-12：所有 256 名随机参与者均完成了研究。四组参与者的基线特征相似。总体而言，中位年龄为 64 岁（IQR 61 至 69），256 名参与者中有 105 名男性（41%）。第28天时，联合组的几何平均抗尖峰蛋白IgG ELISA单位为534U/mL（95% CI 432-660），纯NVX组为556U/mL（95% CI 460-672），几何平均滴度比为0.96（95% CI 0.73-1.27），因此符合非劣效性标准。第28天时，联合组的抗五氯酚钠IgG ELISA单位为507U/mL（95% CI 416-619），纯PCV20组为592U/mL（95% CI 485-723）。三个活性治疗组的局部和全身反应性相似。未发现安全问题或严重不良事件：结论：NVX-CoV2601与PCV20联合用药后的免疫原性并不比单独使用NVX-CoV2601差。考虑到相似的安全性和致病反应，我们的研究结果可能有助于克服对同时接种疫苗的担忧，并为联合疫苗的开发铺平道路：Novavax.
Immunogenicity, safety, and reactogenicity of concomitant administration of the novavax vaccine against Omicron XBB.1.5 (NVX-CoV2601) and a 20-valent pneumococcal conjugate vaccine in adults aged ≥60 years: A randomised, double-blind, placebo-controlled, non-inferiority trial.
Objectives: There is conflicting evidence as to whether the combined administration of two vaccines can lead to poorer immunogenicity and reactogenicity. The co-administration of the Omicron-adapted COVID-19 vaccine from Novavax (NVX-CoV2601) and a 20-valent pneumococcal conjugate vaccine (PCV20) has not been previously investigated.
Methods: In this randomised, double-blind, placebo-controlled, non-inferiority trial, immunocompetent participants aged ≥60 years were randomised in a 1:1:1:1 ratio to four groups: NVX-CoV2601 plus PCV20 (combination group); NVX-CoV2601 plus placebo (NVX-only group); PCV20 plus placebo (PCV20-only group); or placebo plus placebo (placebo group). The primary outcome was Omicron-specific anti-spike protein IgG ELISA units at day 28 in the combination group compared with the NVX-only group. Non-inferiority was established if the lower limit of the two-sided 95% CI of the geometric mean titre ratio was above the non-inferiority margin of 0.67. Secondary outcomes included anti-pneumococcal capsular polysaccharide (PCP) IgG ELISA units. Solicited local and systemic adverse events were collected for 7 days after vaccination. This study was registered with ClinicalTrials.gov, number NCT05767606, and the EU Clinical Trials Register, EudraCT number 2022-004118-12.
Results: All 256 randomised participants completed the study. The baseline characteristics were similar in the four groups. Overall, the median age was 64 (IQR 61 to 69) and 105 (41%) of 256 were male. At day 28, the geometric mean anti-spike protein IgG ELISA units were 534 U/mL (95% CI 432-660) in the combination group and 556 U/mL (95% CI 460-672) in the NVX-only group, resulting in a geometric mean titre ratio of 0.96 (95% CI 0.73-1.27), thereby meeting the criteria for non-inferiority. Anti-PCP IgG ELISA units at day 28 were 507 U/mL (95% CI 416-619) in the combination group and 592 U/mL (95% CI 485-723) in the PCV20-only group. Local and systemic reactogenicity was similar in the three active treatment groups. No safety concerns or serious adverse events were observed.
Conclusions: Immunogenicity following co-administration of NVX-CoV2601 with PCV20 was non-inferior to administration of NVX-CoV2601 alone. Given the similar safety and reactogenicity profile, our findings may help to overcome concerns about concomitant vaccination and pave the way for combination vaccines.
期刊介绍：
The Journal of Infection publishes original papers on all aspects of infection - clinical, microbiological and epidemiological. The Journal seeks to bring together knowledge from all specialties involved in infection research and clinical practice, and present the best work in the ever-changing field of infection.
Each issue brings you Editorials that describe current or controversial topics of interest, high quality Reviews to keep you in touch with the latest developments in specific fields of interest, an Epidemiology section reporting studies in the hospital and the general community, and a lively correspondence section.
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