Institute of Human Genetics, School of Medicine, Pontificia Universidad Javeriana, Bogotá, Colombia.
Department of Clinical Epidemiology and Biostatistics, School of Medicine, Pontificia Universidad Javeriana, Bogotá, Colombia.
Front Immunol. 2023 Jul 27;14:1241038. doi: 10.3389/fimmu.2023.1241038. eCollection 2023.
The SARS CoV-2 antibody and CD4 T cell responses induced by natural infection and/or vaccination decline over time and cross-recognize other viral variants at different levels. However, there are few studies evaluating the levels and durability of the SARS CoV-2-specific antibody and CD4 T cell response against the Mu, Gamma, and Delta variants. Here, we examined, in two ambispective cohorts of naturally-infected and/or vaccinated individuals, the titers of anti-RBD antibodies and the frequency of SARS-CoV-2-specific CD4 T cells up to 6 months after the last antigen exposure. In naturally-infected individuals, the SARS-CoV-2 antibody response declined 6 months post-symptoms onset. However, the kinetic observed depended on the severity of the disease, since individuals who developed severe COVID-19 maintained the binding antibody titers. Also, there was detectable binding antibody cross-recognition for the Gamma, Mu, and Delta variants, but antibodies poorly neutralized Mu. COVID-19 vaccines induced an increase in antibody titers 15-30 days after receiving the second dose, but these levels decreased at 6 months. However, as expected, a third dose of the vaccine caused a rise in antibody titers. The dynamics of the antibody response upon vaccination depended on the previous SARS-CoV-2 exposure. Lower levels of vaccine-induced antibodies were associated with the development of breakthrough infections. Vaccination resulted in central memory spike-specific CD4 T cell responses that cross-recognized peptides from the Gamma and Mu variants, and their duration also depended on previous SARS-CoV-2 exposure. In addition, we found cross-reactive CD4 T cell responses in unexposed and unvaccinated individuals. These results have important implications for vaccine design for new SARS-CoV-2 variants of interest and concern.
SARS-CoV-2 抗体和 CD4 T 细胞反应由自然感染和/或接种引起，随着时间的推移而下降，并在不同水平上交叉识别其他病毒变体。然而，评估针对 Mu、Gamma 和 Delta 变体的 SARS-CoV-2 特异性抗体和 CD4 T 细胞反应的水平和持久性的研究较少。在这里，我们在两个前瞻性自然感染和/或接种个体队列中检查了最后一次抗原暴露后长达 6 个月时的抗 RBD 抗体滴度和 SARS-CoV-2 特异性 CD4 T 细胞的频率。在自然感染的个体中，SARS-CoV-2 抗体反应在症状出现后 6 个月下降。然而，观察到的动力学取决于疾病的严重程度，因为患有严重 COVID-19 的个体保持了结合抗体滴度。此外，针对 Gamma、Mu 和 Delta 变体存在可检测的结合抗体交叉识别，但抗体对 Mu 的中和能力很差。COVID-19 疫苗在接受第二剂后 15-30 天引起抗体滴度增加，但这些水平在 6 个月时下降。然而，正如预期的那样，疫苗的第三剂引起了抗体滴度的上升。接种疫苗后的抗体反应动力学取决于先前 SARS-CoV-2 的暴露情况。疫苗诱导的抗体水平较低与突破性感染的发展有关。接种疫苗导致针对 Spike 的中央记忆 CD4 T 细胞反应，这些反应交叉识别来自 Gamma 和 Mu 变体的肽，其持续时间也取决于先前 SARS-CoV-2 的暴露情况。此外，我们在未暴露和未接种疫苗的个体中发现了交叉反应性 CD4 T 细胞反应。这些结果对针对新的 SARS-CoV-2 变体的疫苗设计具有重要意义。
