Abstract
SARS-CoV-2 inactivated vaccines have shown remarkable efficacy in clinical trials, especially in reducing severe illness and casualty. However, the waning of humoral immunity over time has raised concern over the durability of immune memory following vaccination. Thus, we conducted a nonrandomized trial among the healthcare workers (HCWs) to investigate the long-term sustainability of SARS-CoV-2-specific B cells and T cells stimulated by inactivated vaccines and the potential need for a third booster dose. Although neutralizing antibodies elicited by the standard two-dose vaccination schedule dropped from a peak of 29.3 arbitrary units (AU)/mL to 8.8 AU/mL 5 months after the second vaccination, spike-specific memory B and T cells were still detectable, forming the basis for a quick recall response. As expected, the faded humoral immune response was vigorously elevated to 63.6 AU/mL by 7.2 folds 1 week after the third dose along with abundant spike-specific circulating follicular helper T cells in parallel. Meanwhile, spike-specific CD4+ and CD8+ T cells were also robustly elevated by 5.9 and 2.7 folds respectively. Robust expansion of memory pools by the third dose potentiated greater durability of protective immune responses. Another key finding in this trial was that HCWs with low serological response to two doses were not truly “non-responders” but fully equipped with immune memory that could be quickly recalled by a third dose even 5 months after the second vaccination. Collectively, these data provide insights into the generation of long-term immunological memory by the inactivated vaccine, which could be rapidly recalled and further boosted by a third dose.
Highlights
The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to spread across the globe currently[1,2]
We have previously conducted a nonrandomized trial and recruited healthcare workers (HCWs) from a prospective cohort, demonstrating the impact of the circadian rhythm on the immune response induced by a primary two-dose series of the inactivated SARS-CoV-2 vaccine (BBIBP-CorV, Sinopharm, Beijing)[11]
Fifty HCWs from this cohort were volunteered to participate in the current nonrandomized trial to investigate the duration of the primary vaccination regimen and potential benefits of a third dose, given 5 months after the second dose (Fig. 1a)
Summary
The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to spread across the globe currently[1,2]. The rapid spreading of COVID-19 has urged the governments to authorize the emergent use of vaccines against SARS-CoV-23–5. SARS-CoV-2 is an indicator of protective immunity after vaccination or infection[6,7]. NAbs capable of blocking the interaction between the spike protein and its receptor angiotensin-converting enzyme 2 (ACE2) are important for protection from COVID-198. Inducing potent NAbs and long-lasting memory B cells is the primary goal of SARS-CoV-2 vaccines. Two doses of mRNA or inactivated vaccines are capable of inducing potent neutralizing antibody responses[3,9,10]. Our previous study further demonstrated that inactivated vaccines elicited SARS-CoV-2-specific memory B cells[11], which are important for a rapid and robust recall of protective responses against viral infection.
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