Long-term assessment of anti-SARS-CoV-2 antibody levels post-pandemic: Tracking the dynamics after two, three, and four COVID-19 vaccine doses

Background: Given the limited available data about to the number of vaccine doses administered over an extended time in Iran, the immune status of vaccinated individuals and any potential disparities in this regard among those who received different numbers of vaccine doses remain unknown. Therefore, this study aimed to assess humoral immunity of individuals who received different doses of the COVID-19 vaccines in Iran. Methods: This study was conducted from February, 2022 to December 2023 including 605 vaccinated subjects. The durability of anti-spike, anti-nucleocapsid (NCP), neutralizing antibody, and interferon-gamma (IFN gamma) was evaluated at least 6 months after the last vaccination, as well as 60 and 120 days after it, in individuals who received two or three doses of the COVID-19 vaccine. Furthermore, the evaluation of humoral and cellular response was performed before the fourth dose (second booster) as well as 21 and 60 days thereafter. Results: The 3-dose group showed significantly higher levels of anti-spike, neutralizing antibodies, and IFN gamma compared to the 2-dose group. Both the 2-dose and 3-dose groups experienced a slight decrease in the dynamic of SARS-CoV-2 Abs, though the associated levels remained within a positive range. After receiving the fourth dose of PastoCovac, most participants had significantly high levels of anti-spike, neutralizing antibodies, and IFN-gamma, regardless of the type of three-dose regimen they had previously received. The average antibody titer decreased after 60 days from the fourth dose, but remained relatively stable during the follow-up period. Conclusion: This study found that the level of anti-SARS-CoV-2 antibodies and IFN-gamma, as well as their durability, were still within a positive range in 2-dose and 3-dose vaccinated groups over the long-term followup. Furthermore, PastoCovac vaccine enhanced humoral and cellular immune responses and could be recommended as a booster dose for individuals previously vaccinated with any previously administered COVID-19 vaccine. (c) 2025 The Author(s). Published by Elsevier Ltd on behalf of King Saud Bin Abdulaziz University for Health Sciences. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).