Piano Mortari Eva, Ferrucci Francesca, Zografaki Irini, Carsetti Rita, Pacelli Luciano
B Lymphocytes Unit, Bambino Gesù Children's Hospital, istituto di ricovero e cura a carattere scientifico (IRCCS), Rome, Italy.
Medical Department, Covid Franchise, Pfizer s.r.l., Rome, Italy.
Front Immunol. 2025 Mar 18;16:1535014. doi: 10.3389/fimmu.2025.1535014. eCollection 2025.
Vaccines against COVID-19 have high efficacy and low rates of adverse events. However, none of the available vaccines provide sterilizing immunity, and reinfections remain possible. This review aims to summarize the immunological responses elicited by different immunization strategies, examining the roles of homologous and heterologous vaccination and hybrid immunity. Homologous vaccination regimens exhibit considerable variation in immune responses depending on the vaccine platform, particularly concerning antibody titers, B cell activation, and T cell responses. mRNA vaccines, such as mRNA-1273 and BNT162b2, consistently generate higher and more durable levels of neutralizing antibodies and memory B cells compared to adenovirus-based vaccines like Ad26.COV2.S and ChAdOx1. The combination of two distinct vaccine platforms, each targeting different immune pathways, seems to be more effective in promoting long-lasting B cell responses and potent T cell responses. The high heterogeneity of the available studies, the different dosing schemes, the succession of new variants, and the subjects' immunological background do not allow for a definitive conclusion. Overall, heterologous vaccination strategies, combining sequentially viral vector and mRNA may deliver a more balanced and robust humoral and cellular immune response compared to homologous regimens. Hybrid immunity, which arises from SARS-CoV-2 infection preceded or followed by vaccination produces markedly stronger immune responses than either vaccination or infection alone. The immune response to SARS-CoV-2 variants of concern varies depending on both the vaccine platform and prior infection status. Hybrid immunity leads to a broader antibody repertoire, providing enhanced neutralization of variants of concern. Heterologous vaccination and hybrid immunity may provide further opportunities to enhance immune responses, offering broader protection and greater durability of immunity. However, from all-cause mortality, symptomatic or severe COVID, and serious adverse events at present it is not possible to infer different effects between homologous and heterologous schemes. Next-generation vaccines could involve tweaks to these designs or changes to delivery mechanisms that might improve performance.
针对新型冠状病毒肺炎（COVID-19）的疫苗具有高效性和低不良事件发生率。然而，现有的疫苗均不能提供无菌免疫，再次感染仍有可能发生。本综述旨在总结不同免疫策略引发的免疫反应，探讨同源和异源疫苗接种以及混合免疫的作用。同源疫苗接种方案的免疫反应因疫苗平台而异，尤其在抗体滴度、B细胞活化和T细胞反应方面。与基于腺病毒的疫苗（如Ad26.COV2.S和ChAdOx1）相比，mRNA疫苗（如mRNA-1273和BNT162b2）始终能产生更高且更持久水平的中和抗体和记忆B细胞。两种不同疫苗平台的组合，每种针对不同的免疫途径，似乎在促进持久的B细胞反应和强效的T细胞反应方面更有效。现有研究的高度异质性、不同的给药方案、新变种的相继出现以及受试者的免疫背景使得无法得出明确结论。总体而言，与同源方案相比，依次结合病毒载体和mRNA的异源疫苗接种策略可能会产生更平衡、更强健的体液和细胞免疫反应。由接种疫苗之前或之后的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染所产生的混合免疫，其产生的免疫反应明显强于单独接种疫苗或感染。对关注的SARS-CoV-2变种的免疫反应因疫苗平台和既往感染状态而异。混合免疫导致更广泛的抗体库，增强了对关注变种的中和作用。异源疫苗接种和混合免疫可能提供进一步增强免疫反应的机会，提供更广泛的保护和更持久的免疫力。然而，从全因死亡率、有症状或严重的COVID-19以及严重不良事件来看，目前无法推断同源和异源方案之间的不同效果。下一代疫苗可能涉及对这些设计的调整或递送机制的改变，这可能会提高性能。
