LAUSR

Several countries have achieved high two-dose COVID-19 vaccination coverage but have been unable to control the spread of SARS-CoV-2. A third dose (booster) has been recommended worldwide to achieve better protection against the newly emerged SARS-CoV-2 omicron variant. Several two-dose primary series regimens have been widely approved and implemented, including two-dose CoronaVac (CV), BBIBP-CorV (BBIBP), BNT162b2 (BNT), mRNA-1273, and AZD1222 (AZ) vaccines. Many countries, including Thailand, have implemented a mix-and-match primary series regimen, which is CV followed by AZ vaccine [1]. Our previous study demonstrated that the third dose of AZ, BNT or mRNA-1273 vaccine administered to individuals receiving two doses of an inactivated vaccine (CV and BBIBP) as their primary series can induce high levels of binding and neutralizing antibodies against SARS-CoV-2 [2,3]. Our previous study demonstrated that the mRNA or viral-vectored vaccine used as a booster following twodose AZ initial course can boost cellular immunity and neutralizing antibody responses against wild-type and SARS-CoV-2 variants of concern including delta and omicron (BA.1 and BA.2), with acceptable safety profiles [4]. In addition, in individuals vaccinated with mix-and-match primary series regimens (CV followed by AZ), a third dose of AZ, BNT or mRNA-1273 induces a high level of anti-RBD IgG and neutralizing antibody titers against omicron BA.1 and BA.2 [5]. The objective of this article is to summarize the results from the previously published studies and make a recommendation on the use of third-dose (booster) COVID-19 vaccines in healthy adults who were primary immunized with different two-dose schedules. The total receptor-binding domain (RBD)-specific immunoglobulin (Ig) antibody response following the standard dose of BNT vaccine booster was compared among Thai individuals who received five different regimens of two-dose primary series COVID-19 vaccine as previously published [2–4] or are currently under review [5]. This information will increase awareness and promote vaccine acceptance among different two-dose schedules vaccinated individuals and healthcare providers. Data from previous studies comprising 234 healthy participants who were Thai individuals 18 years of age or older were analyzed. All participants had received twodose primary series COVID-19 vaccine with no history of laboratory-confirmed SARS-CoV-2 infection. Participants in the BBIBP/BBIBP, CV/CV, CV/AZ and AZ/AZ group received the third-dose BNT and had blood testing preand post-booster. Participants in the PZ/PZ group were healthy individuals who sought antibody testing at 4 weeks post-booster. Therefore, blood samples at prebooster were not available in this group. All participants were enrolled at the clinical trial unit of the Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University between September 2021 and January 2022. The secondand third-dose vaccination interval was between 4 and 6 months. Blood collection was performed at four weeks post-booster. All sera samples were tested for total RBD Ig specific to SARS-CoV-2 using an electrochemiluminescence immunoassay (ECLIA) (Roche Diagnostics, Basel, Switzerland). The baseline demographic characteristics of participants in all groups who received two-dose BBIBP (n = 52), CV (n = 54), AZ (n = 61), BNT (n = 12) and mixand-match CV/AZ (n = 55) vaccine were generally comparable. However, the mean age of participants who received two-dose AZ vaccine was significantly higher than other groups (p < 0.001) due to the prioritization of this vaccine in the elderly during the initial implementation (Table S1). No significant differences in sex were observed between the groups. The results showed that at baseline (pre-booster), the geometric mean ratios (GMRs) of the CV/CV, CV/AZ, and AZ/AZ prime individuals compared to the BBIBP/BBIBP group were 5.7 (3.6–9.1), 46.8 (30.4–71.8) and 29.6 (19.4– 45.0), respectively (Table S2). At 28 days post-booster vaccination with BNT, all groups demonstrated