Introduction: The induction and speed of production of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) immune biomarkers may vary by type and number of inoculated vaccine doses. This study aimed to explore variations in SARS-CoV-2 anti-spike (anti-S), anti-nucleocapsid (anti-N), and neutralizing immunoglobulin G (IgG) antibodies, and T-cell response by type and number of SARS-CoV-2 vaccine doses received.

Methods: In a naturally exposed and SARS-CoV-2-vaccinated population, we quantified the anti-S, anti-N, and neutralizing IgG antibody concentration and assessed T-cell response. Data on socio-demographics, medical history, and history of SARS-CoV-2 infection and vaccination were collected. Furthermore, nasal swabs were collected to test for SARS-CoV-2 infection. Confounder-adjusted association between having equal or more than a median concentration of the three IgG antibodies and T-cell response by number and type of the inoculated vaccines was quantified.

Results: We surveyed 952 male participants with a mean age of 35.5 years ± 8.4 standard deviations. Of them, 52.6% were overweight/obese, and 11.7% had at least one chronic comorbidity. Of the participants, 1.4, 0.9, 20.2, 75.2, and 2.2% were never vaccinated, primed with only one dose, primed with two doses, boosted with only one dose, and boosted with two doses, respectively. All were polymerase chain reaction-negative to SARS-CoV-2. BBIBP-CorV (Sinopharm) was the most commonly used vaccine (92.1%), followed by rAd26-S + rAd5-S (Sputnik V Gam-COVID-Vac) (1.5%) and BNT162b2 (Pfizer-BioNTech) (0.3%). Seropositivity to anti-S, anti-N, and neutralizing IgG antibodies was detected in 99.7, 99.9, and 99.3% of the study participants, respectively. The T-cell response was detected in 38.2% of 925 study participants. Every additional vaccine dose was significantly associated with increased odds of having ≥median concentration of anti-S [adjusted odds ratio (aOR), 1.34; 95% confidence interval (CI): 1.02-1.76], anti-N (aOR, 1.35; 95% CI: 1.03-1.75), neutralizing IgG antibodies (aOR, 1.29; 95% CI: 1.00-1.66), and a T-cell response (aOR, 1.48; 95% CI: 1.12-1.95). Compared with boosting with only one dose, boosting with two doses was significantly associated with increased odds of having ≥median concentration of anti-S (aOR, 13.8; 95% CI: 1.78-106.5), neutralizing IgG antibodies (aOR, 13.2; 95% CI: 1.71-101.9), and T-cell response (aOR, 7.22; 95% CI: 1.99-26.5) although not with anti-N (aOR, 0.41; 95% CI: 0.16-1.08). Compared with priming and subsequently boosting with BBIBP-CorV, all participants who were primed with BBIBP-CorV and subsequently boosted with BNT162b2 had ≥median concentration of anti-S and neutralizing IgG antibodies and 14.6-time increased odds of having a T-cell response (aOR, 14.63; 95% CI: 1.78-120.5). Compared with priming with two doses, boosting with the third dose was not associated, whereas boosting with two doses was significantly associated with having ≥median concentration of anti-S (aOR, 14.20; 95% CI: 1.85-109.4), neutralizing IgG (aOR, 13.6; 95% CI: 1.77-104.3), and T-cell response (aOR, 7.62; 95% CI: 2.09-27.8).

Conclusion: Achieving and maintaining a high blood concentration of protective immune biomarkers that predict vaccine effectiveness is very critical to limit transmission and contain outbreaks. In this study, boosting with only one dose or with only BBIBP-CorV after priming with BBIBP-CorV was insufficient, whereas boosting with two doses, particularly boosting with the mRNA-based vaccine, was shown to be associated with having a high concentration of anti-S, anti-N, and neutralizing IgG antibodies and producing an efficient T-cell response.