Rebecca Clark, Sam Davies, Jorge Labrador, Paul Loubet, Silvina Natalini Martínez, Helena Moza Moríñigo, Jean-François Nicolas, Mercè Pérez Vera, Mika Rämet, Maria Henar Rebollo-Rodrigo, Iván Sanz-Muñoz, Nancy Dezutter, Sophie Germain, Marie-Pierre David, Amulya Jayadev, Hiwot Amare Hailemariam, Shady Kotb, Nadia Meyer
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Primary objectives were to demonstrate the non-inferiority of FLU-aQIV and RSVPreF3 OA co-administration versus sequential administration in terms of hemagglutination inhibition (HI) titers for each FLU-aQIV strain and RSV-A and RSV-B neutralization titers, 1 month post-vaccination. Reactogenicity and safety were also assessed.</p><p><strong>Results: </strong>Overall, 1045 participants were vaccinated (Co-Ad: 523; Control: 522). Non-inferiority of FLU-aQIV and RSVPreF3 OA co-administration versus sequential administration was demonstrated in terms of HI titers for the A/Victoria(H1N1), B/Victoria, and B/Yamagata influenza strains and RSV-A neutralization titers (upper limits [ULs] of 95% confidence intervals [CIs] for adjusted geometric mean titer [GMT] ratios [Control/Co-Ad] ≤1.50) but not for A/Darwin(H3N2) HI titers (95% CI UL = 1.53). The immune response to A/Darwin(H3N2) was further assessed post-hoc using a microneutralization assay; the post-vaccination adjusted GMT ratio (Control/Co-Ad) was 1.23 (95% CI: 1.06-1.42, ie, UL ≤1.50), suggesting an adequate immune response to A/Darwin(H3N2) following co-administration. RSV-B neutralization titers were comparable between groups (95% CI UL for adjusted GMT ratio ≤1.50). Solicited adverse events were mostly mild or moderate and transient; unsolicited and serious adverse event rates were balanced between groups.</p><p><strong>Conclusions: </strong>Adjuvanted FLU-aQIV and RSVPreF3 OA had acceptable reactogenicity/safety profiles when co-administered in ≥65-year-olds, without clinically relevant interference with the immune responses to either vaccine.</p><p><strong>Clinical trials registration: </strong>NCT05568797.</p>","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":" ","pages":"1088-1098"},"PeriodicalIF":8.2000,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11478588/pdf/","citationCount":"0","resultStr":"{\"title\":\"Safety and Immunogenicity of Respiratory Syncytial Virus Prefusion F Protein Vaccine when Co-administered with Adjuvanted Seasonal Quadrivalent Influenza Vaccine in Older Adults: A Phase 3 Randomized Trial.\",\"authors\":\"Rebecca Clark, Sam Davies, Jorge Labrador, Paul Loubet, Silvina Natalini Martínez, Helena Moza Moríñigo, Jean-François Nicolas, Mercè Pérez Vera, Mika Rämet, Maria Henar Rebollo-Rodrigo, Iván Sanz-Muñoz, Nancy Dezutter, Sophie Germain, Marie-Pierre David, Amulya Jayadev, Hiwot Amare Hailemariam, Shady Kotb, Nadia Meyer\",\"doi\":\"10.1093/cid/ciae365\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>We evaluated co-administration of adjuvanted seasonal quadrivalent influenza vaccine (FLU-aQIV) and respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVPreF3 OA) in ≥65-year-olds.</p><p><strong>Methods: </strong>This phase 3, open-label trial randomized ≥65-year-olds to receive FLU-aQIV and RSVPreF3 OA concomitantly (Co-Ad) or sequentially, 1 month apart (Control). Primary objectives were to demonstrate the non-inferiority of FLU-aQIV and RSVPreF3 OA co-administration versus sequential administration in terms of hemagglutination inhibition (HI) titers for each FLU-aQIV strain and RSV-A and RSV-B neutralization titers, 1 month post-vaccination. Reactogenicity and safety were also assessed.</p><p><strong>Results: </strong>Overall, 1045 participants were vaccinated (Co-Ad: 523; Control: 522). Non-inferiority of FLU-aQIV and RSVPreF3 OA co-administration versus sequential administration was demonstrated in terms of HI titers for the A/Victoria(H1N1), B/Victoria, and B/Yamagata influenza strains and RSV-A neutralization titers (upper limits [ULs] of 95% confidence intervals [CIs] for adjusted geometric mean titer [GMT] ratios [Control/Co-Ad] ≤1.50) but not for A/Darwin(H3N2) HI titers (95% CI UL = 1.53). 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引用次数: 0
摘要
背景：我们评估了在≥65岁的老年人中同时接种佐剂季节性四价流感疫苗（FLU-aQIV）和基于F蛋白的呼吸道合胞病毒（RSV）预融合疫苗（RSVPreF3 OA）的情况：这项 3 期开放标签试验随机分配年龄≥65 岁的患者同时接种 FLU-aQIV 和 RSVPreF3 OA（联合接种），或相隔 1 个月依次接种（对照组）。主要目的是证明FLU-aQIV和RSVPreF3 OA同时接种与顺序接种相比，在疫苗接种后1个月，各株FLU-aQIV的血凝抑制（HI）滴度以及RSV-A和RSV-B的中和滴度方面无劣效。此外，还对反应原性和安全性进行了评估：共有 1045 人接种了疫苗（联合免疫：523 人；对照组：522 人）。在甲型/乙型/Victoria(H1N1)、乙型/Victoria和乙型/Yamagata流感菌株的HI滴度和RSV-A中和滴度方面，FLU-aQIV和RSVPreF3 OA联合给药与连续给药相比无劣效（调整后几何平均滴度[GMT]比[对照组/联合给药组]≤1.50的95%置信区间[CI]上限[UL]），但在甲型/乙型/Victoria(H1N1)、乙型/Victoria和乙型/Yamagata流感菌株的HI滴度和RSV-A中和滴度方面无劣效。50），但对 A/Darwin(H3N2) HI 滴度的影响不大（95% CI UL = 1.53）。接种后调整的 GMT 比值（对照组/联合用药组）为 1.23（95% CI：1.06-1.42，即 UL ≤1.50），表明联合用药后对 A/Darwin(H3N2)产生了充分的免疫反应。各组之间的RSV-B中和滴度相当（调整后GMT比值的95% CI UL≤1.50）。主动发生的不良反应大多为轻度或中度，且为一过性；主动发生的不良反应和严重不良反应的发生率在各组之间保持平衡：临床试验注册：临床试验注册：NCT05568797。
Safety and Immunogenicity of Respiratory Syncytial Virus Prefusion F Protein Vaccine when Co-administered with Adjuvanted Seasonal Quadrivalent Influenza Vaccine in Older Adults: A Phase 3 Randomized Trial.
Background: We evaluated co-administration of adjuvanted seasonal quadrivalent influenza vaccine (FLU-aQIV) and respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVPreF3 OA) in ≥65-year-olds.
Methods: This phase 3, open-label trial randomized ≥65-year-olds to receive FLU-aQIV and RSVPreF3 OA concomitantly (Co-Ad) or sequentially, 1 month apart (Control). Primary objectives were to demonstrate the non-inferiority of FLU-aQIV and RSVPreF3 OA co-administration versus sequential administration in terms of hemagglutination inhibition (HI) titers for each FLU-aQIV strain and RSV-A and RSV-B neutralization titers, 1 month post-vaccination. Reactogenicity and safety were also assessed.
Results: Overall, 1045 participants were vaccinated (Co-Ad: 523; Control: 522). Non-inferiority of FLU-aQIV and RSVPreF3 OA co-administration versus sequential administration was demonstrated in terms of HI titers for the A/Victoria(H1N1), B/Victoria, and B/Yamagata influenza strains and RSV-A neutralization titers (upper limits [ULs] of 95% confidence intervals [CIs] for adjusted geometric mean titer [GMT] ratios [Control/Co-Ad] ≤1.50) but not for A/Darwin(H3N2) HI titers (95% CI UL = 1.53). The immune response to A/Darwin(H3N2) was further assessed post-hoc using a microneutralization assay; the post-vaccination adjusted GMT ratio (Control/Co-Ad) was 1.23 (95% CI: 1.06-1.42, ie, UL ≤1.50), suggesting an adequate immune response to A/Darwin(H3N2) following co-administration. RSV-B neutralization titers were comparable between groups (95% CI UL for adjusted GMT ratio ≤1.50). Solicited adverse events were mostly mild or moderate and transient; unsolicited and serious adverse event rates were balanced between groups.
Conclusions: Adjuvanted FLU-aQIV and RSVPreF3 OA had acceptable reactogenicity/safety profiles when co-administered in ≥65-year-olds, without clinically relevant interference with the immune responses to either vaccine.
期刊介绍：
Clinical Infectious Diseases (CID) is dedicated to publishing original research, reviews, guidelines, and perspectives with the potential to reshape clinical practice, providing clinicians with valuable insights for patient care. CID comprehensively addresses the clinical presentation, diagnosis, treatment, and prevention of a wide spectrum of infectious diseases. The journal places a high priority on the assessment of current and innovative treatments, microbiology, immunology, and policies, ensuring relevance to patient care in its commitment to advancing the field of infectious diseases.
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