Antibody Response (IgM and IgG) After Two Doses of Immunization Against SARS-CoV-2 and Comparison of Two Different Third Dose Administrations
Authors: Sağlık İmran , Payaslıoğlu Melda , Başkılıç Aydın Reyhan , Ener Beyza , Ağca Harun , Tüzemen Nazmiye Ülkü , Özakın Cüneyt , Akalın Emin Halis 
Published: January 2023

Türkiye's first SARS-CoV-2 vaccination campaign started with an inactivated vaccine (Sinovac Life Sciences Co., Ltd., Beijing, China) mid-January 2021 for healthcare workers. The second dose was administered at an interval of 21 days-one month. As of July 2021 (4-4.5 months after the second dose), the Republic of Türkiye Ministry of Health suggested the third vaccination dose for healthcare workers and people over 50. The individuals could select between the choice of CoronaVac or an mRNA vaccine BNT162b2 (Pfizer‐BioNTech, Inc) for the third dose vaccination. Thus, a heterogeneous immunization emerged in society. This study is aimed to investigate the humoral response (IgG and IgM) after two doses of the SARS-CoV-2 vaccine and the possible effects of factors for this response, as well as to compare the third dose of homogeneous and heterogeneous vaccine administration. The study included 512 volunteers who are 21-65 years old that have been immunized against SARS-CoV-2 in at least two doses, working at Bursa Uludag University Faculty of Medicine Health Application and Research Center. The demographic characteristics of the participants (such as age, gender, and place of duty), background (presence of chronic disease, risky contact for SARS-CoV-2 transmission, and history of COVID-19 infection), and immunization characteristics were obtained with a questionnaire. Participants were divided into five main groups regarding the time elapsed months after the second dose and the type of vaccine administered (CoronaVac or BNT162b2). Group 1b (n=11); (blood samples were taken) one month after the second dose of BNT162b2 vaccine, group1c (n=12); one month after the second dose of CoronaVac, group 2 (n=9); two months after the second dose of CoronaVac vaccine, group 3 (n=27); three months after of CoronaVac vaccine, group 4 (n=418); four months after the second dose of CoronaVac vaccine and group 5 (n=35); five months after the second dose of CoronaVac vaccine. One month later, blood samples were taken from 52 participants in group 4 who received the third dose of the vaccine. In these participants, IgG levels were compared after two different third-dose vaccines [BNT162b2; group 4b (n=30) and CoronaVac; group 4c (n=22)]. SARS-CoV-2 IgM and IgG responses were evaluated by SARS-CoV-2 IgM (Abbott, USA) and IgG Quant II (Abbott, USA) kits on Architect i2000SR (Abbott, USA) autoanalyzer with a chemiluminescent based method at Bursa Uludag University Faculty of Medicine Medical Microbiology Laboratory. In this study, a high rate (>80%) of anti-S IgG seroconversion was observed in all groups given two doses of the SARS-CoV-2 vaccine. The median IgG levels in groups 1b, 1c, 2, 3, 4, and 5 were 4315.3 AU/mL (24-10337), 721.5 AU/mL (154-1430), 842.5 AU/mL (365-4447), 183.0 AU/mL (14-1635), 165.0 AU/mL (4-31796) and 110.0 AU/mL (28-8757), respectively. After CoronaVac vaccination with two doses, groups 3, 4, and 5 had low levels of anti-SARS-CoV-2 IgG compared to group 1c (p values: 0.034, 0.006, and 0.001, respectively). IgM positivity was between 12.5-33.5% in the participants whose blood samples were obtained at one, two, and three months after the vaccination and 3.2-4.3% in the participants after four and five months (p=0.001). The heterogeneous immunization [two doses of CoronaVac and one dose of BNT162b2: median 11084.5 AU/mL (2948-40000)] has provided higher SARS-CoV-2 IgG levels compared to homogeneous immunization [three doses of CoronaVac: median 1707.0 AU/mL (304-8322)] (p<0.001). When the factors that affect the vaccine response were examined four months after two doses of the CoronaVac vaccine, IgM and IgG responses were higher in participants who also had past COVID-19 infection history (p=0.001). Advanced age (>60) was the most critical negative factor in IgG levels (p=0.001). Unlike previous research, it was found that the presence of comorbidity and gender did not affect the vaccine response after four months. Having a high-risk contact history and working in high-risk areas (pandemic ward) did not affect the antibody response. Among the factors evaluated, the only factor affecting IgM positivity was the combination of vaccine and natural immunity. Decreased levels of anti-S IgG antibody three months after the CoronaVac vaccine may affect the protection, especially in advanced age groups. Although this situation creates a guide for the planning of booster doses, the neutralizing antibody and T-cell response are important for protection.