Violán Concepció, Quirant-Sánchez Bibiana, Palau-Antoja Maria, Palacin Dolors, Pradenas Edwards, Trigueros Macedonia, Pera Guillem, Molist Gemma, Fernández-Rivas Gema, Boigués Marc, Isnard Mar, Prat Nuria, Carmona-Cervelló Meritxell, Lamonja-Vicente Noemi, León-Gómez Brenda Biaani, Martínez-Cáceres Eva María, Cardona Pere Joan, Blanco Julià, Massanella Marta, Torán-Monserrat Pere
Unitat de Suport a la Recerca Metropolitana Nord, Institut Universitari d'Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Mare de Déu de Guadalupe 2, Planta 1ª, Mataró, 08303 Barcelona, Spain.
Germans Trias i Pujol Research Institute (IGTP), 08916 Badalona, Spain.
Vaccines (Basel). 2025 Jul 9;13(7):738. doi: 10.3390/vaccines13070738.
: SARS-CoV-2 booster vaccination remains essential to prevent severe COVID-19, particularly in vulnerable populations such as older adults. This study evaluated the durability and dynamics of immune responses following booster vaccination(s) in >65-year-old individuals and examined their association with protection against new infections. : Immune responses were evaluated at 3, 9, and 15 months post-booster, measuring SARS-CoV-2-specific IgG antibodies against spike [IgG(S)] and nucleocapsid [IgG(N)] proteins, neutralizing activity against the Omicron BA.2 variant, and cellular immunity. A subset of participants was tested before booster administration. Regression analyses examined the influence of clinical and immunological factors-including a bivalent fourth dose-on infection risk over time. : Booster vaccination significantly enhanced IgG(S) and neutralizing capacity, peaking at 3 months. Although a decline was observed by 9 months, responses remained above baseline. Individuals with prior SARS-CoV-2 infection exhibited higher IgG(S) levels and neutralizing titers, and significantly lower reinfection rates (15%), compared to uninfected individuals. A fourth vaccine dose further increased IgG(S) levels. While neutralizing capacity was not consistently enhanced by the fourth dose, recipients experienced a lower rate of new infections. Immune trajectory analyses revealed that breakthrough infections elicited strong humoral responses comparable to those seen in previously infected individuals, highlighting the role of hybrid immunity. : In older adults, booster vaccination induces durable immune responses, with hybrid immunity offering enhanced protection. A fourth dose boosts antibody levels and reduces infection risk, supporting its use in this high-risk group. Continued monitoring is needed to determine the long-term effectiveness of boosters, particularly against emerging variants.
：新冠病毒加强针接种对于预防重症新冠肺炎仍然至关重要，尤其是在老年人等脆弱人群中。本研究评估了65岁以上人群接种加强针后免疫反应的持久性和动态变化，并研究了它们与预防新感染的关联。 ：在加强针接种后3个月、9个月和15个月评估免疫反应，测量针对刺突蛋白[IgG(S)]和核衣壳蛋白[IgG(N)]的新冠病毒特异性IgG抗体、针对奥密克戎BA.2变体的中和活性以及细胞免疫。一部分参与者在接种加强针之前进行了检测。回归分析研究了包括二价第四剂在内的临床和免疫因素对随时间推移感染风险的影响。 ：加强针接种显著增强了IgG(S)和中和能力，在3个月时达到峰值。尽管在9个月时观察到有所下降，但反应仍高于基线水平。与未感染个体相比，既往感染过新冠病毒的个体表现出更高的IgG(S)水平和中和滴度，且再感染率显著更低(15%)。第四剂疫苗进一步提高了IgG(S)水平。虽然第四剂并没有持续增强中和能力，但接种者的新感染率较低。免疫轨迹分析显示，突破性感染引发了与既往感染个体相当的强烈体液反应，突出了混合免疫的作用。 ：在老年人中，加强针接种可诱导持久的免疫反应，混合免疫提供了更强的保护。第四剂可提高抗体水平并降低感染风险，支持在这一高风险人群中使用。需要持续监测以确定加强针的长期有效性，尤其是针对新出现的变体。
