Time-course analysis of antibody and cytokine response after the third SARS-CoV-2 vaccine dose

Abstract

The widespread administration of an additional dose of the SARS-CoV-2 vaccine has been promoted across adult populations, demonstrating a robust immune response against COVID-19. Longitudinal studies provide crucial data on the durability of immune response after the third vaccination. This study aims to explore the antibody response, neutralizing activity, and cytokine response against the SARS-CoV-2 ancestral strain (wild-type) and its variants during the timeline before and after the administration of the third vaccine dose. Anti-spike antibody titers and neutralizing antibodies blocking ACE2 binding to spike antigens were measured in 62 study participants at baseline, and on days 7, 21, and 180 post-vaccination. Cytokine levels were assessed at the same points except for day 180, with an additional measurement on day 3 post-vaccination. The analysis revealed no substantial variation in anti-spike antibody titer against the SARS-CoV-2 ancestral strain between the pre-vaccination phase and three days following the third dose. However, a significant nine-fold increase in these titers was observed by day 7, maintained until day 21. Although a decrease was observed by day 180, all participants still had detectable antibody levels. A similar trend was noted for neutralizing antibodies, with a four-fold rise by day 7 post-vaccination. At day 180, a diminution of neutralizing antibody titers was evident for both wild-type and all variants, including Omicron subvariant. A transient increase in cytokine activity, notably involving components of the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway, such as CXCL10 and IL-10, was observed within three days after the third dose. This study underscores a distinct amplification of humoral immune response seven days following the third SARS-CoV-2 vaccine dose and observes a decline in neutralizing antibody titers 180 days following the third dose, thus indicating the temporal humoral effectiveness of booster vaccination. A short-term cytokine surge, notably involving the JAK/STAT pathway, highlights the dynamic immune modulation post-vaccination.