The coronavirus disease 2019 (COVID-19) pandemic has become a severe healthcare problem worldwide since the first outbreak in late December 2019. Currently, the COVID-19 vaccine has been used in many countries, but it is still unable to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, despite patients receiving full vaccination doses. Therefore, we aimed to appraise the booster effect of the different platforms of vaccines, including inactivated vaccine (BBIBP), viral vector vaccine (AZD122), and mRNA vaccine (BNT162b2), in healthy adults who received the full dose of inactivated vaccine (CoronaVac). The booster dose was safe with no serious adverse events. Moreover, the immunogenicity indicated that the booster dose with viral vector and mRNA vaccine achieved a significant proportion of Ig anti-receptor binding domain (RBD), IgG anti-RBD, and IgA anti-S1 booster response. In contrast, inactivated vaccine achieved a lower booster response than others. Consequently, the neutralization activity of vaccinated serum had a high inhibition of over 90% against SARS-CoV-2 wild-type and their variants (B.1.1.7–alpha, B.1.351–beta, and B.1.617.2–delta). In addition, IgG anti-nucleocapsid was observed only among the group that received the BBIBP booster. Our study found a significant increase in levels of IFN-ɣ secreting T-cell response after the additional viral vector or mRNA booster vaccination. This study showed that administration with either viral vector (AZD1222) or mRNA (BNT162b2) boosters in individuals with a history of two doses of inactivated vaccine (CoronaVac) obtained great immunogenicity with acceptable adverse events.

Coronavirus disease 2019 (COVID-19) booster vaccination is being comprehensively evaluated globally due to waning immunity and the emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Therefore, this study aimed to evaluate antibody responses in individuals vaccinated with two doses of the BBIBP-CorV vaccine and to explore the boosting effect of the different vaccine platforms in BBIBP-CorV-primed healthy adults, including a viral vector vaccine (AZD122) and mRNA vaccines (BNT162b2 and mRNA-1273). The results showed that in the BBIBP-CorV prime group, the total receptor-binding domain (RBD) immunoglobulin (Ig) and anti-RBD IgG levels waned significantly at three months after receiving the second dose. However, after the booster, RBD-specific binding antibody levels increased. Neutralizing antibody measured by a surrogate neutralization test showed inhibition over 90% against the SARS-CoV-2 delta variant but less than 70% against the omicron variant after the third dose on day 28. All booster vaccines could induce the total IFN-ɣ T-cell response. The reactogenicity was acceptable and well-tolerated without serious adverse events. This study supports the administration of the third dose with either a viral vector or mRNA vaccine for BBIBP-CorV-primed individuals to stimulate antibody and T-cell responses.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the waning of immunity in vaccinated individuals is resulting in increased numbers of SARS-CoV-2 breakthrough infections. This study investigated binding antibody responses and neutralizing activities against SARS-CoV-2 variants, in patients with COVID-19 who had been fully vaccinated with CoronaVac (n = 77), individuals who had been fully vaccinated with CoronaVac but had not contracted COVID-19 (n = 170), and individuals who had received AZD1222 as a third vaccination (n = 210). Breakthrough infection was generally detected approximately 88 days after the second CoronaVac vaccination (interquartile range 68–100 days). Blood samples were collected at a median of 34 days after infection. Binding antibody levels in sera from patients with breakthrough infection were significantly higher than those in individuals who had received AZD1222 as a third vaccination. However, neutralizing activities against wild-type and variants, including alpha (B.1.1.7), beta (B.1.351), and delta (B.1.617.2), were comparable in patients with breakthrough infections and individuals who received a third vaccination with AZD1222, which exceeds 90%. Omicron (B.1.1.529) was neutralized less effectively by serum from breakthrough infection patients, with a 6.3-fold reduction compared to delta variants. The study suggests that breakthrough infection after two doses of an inactivated vaccine can induce neutralizing antibodies against omicron. Further investigation is needed to assess the long-term persistence of antibodies against the omicron variant.

This study examined the neutralizing activity and receptor-binding domain (RBD) antibody levels against wild-type and omicron BA.1 and BA.2 variants in individuals who received three doses of COVID-19 vaccination. The relationship between the anti-RBD IgG against wild-type and live virus neutralizing antibody titers against omicron BA.1 and BA.2 variants was examined. In total, 310 sera samples from individuals after booster vaccination (third-dose) were tested for specific IgG wild-type SARS-CoV-2 RBD and the omicron BA.1 surrogate virus neutralization test (sVNT). The live virus neutralization assay against omicron BA.1 and BA.2 was performed using the foci-reduction neutralization test (FRNT50). The anti-RBD IgG strongly correlated with FRNT50 titers against BA.1 and BA.2. Non-linear regression showed that anti-RBD IgG at the cut-off value ≥148 BAU/mL and ≥138 BAU/mL were related to the threshold for FRNT50 titers ≥20 against BA.1 and BA.2, respectively. A moderate correlation was observed between the sVNT and FRNT50 titers. At FRNT50 titers ≥20, the predicted sVNT for BA.1 and BA.2 was ≥10.57% and ≥11.52%, respectively. The study identified anti-RBD IgG and sVNT levels that predict detectable neutralizing antibodies against omicron variants. Assessment and monitoring of protective immunity support vaccine policies and will help identify optimal timing for booster vaccination.

The Coronavirus disease 2019 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), continues to surge despite the widespread use of vaccination. In Thailand, more than 77% and 39% of the population received two doses and three doses of COVID-19 vaccines as of December 2022, respectively. In addition, during the Omicron predominant period in 2022, more than 70% of Thai individuals have been infected. To gain comprehensive insight into SARS-CoV-2 antibody dynamics following vaccination or following vaccination and infection (hybrid immunity), we performed a cross-sectional analysis of sera samples from individuals who received COVID-19 vaccination and/or have been infected with COVID-19 in Thailand between January 2021 and December 2022. A total of 4126 samples were collected. Humoral immunity was evaluated by quantifying the immunoglobulin (including IgG, IgM, and IgA isotypes) specific to the SARS-CoV-2 receptor-binding domain (RBD) or Ig anti-RBD. The results showed that individuals who received two-dose vaccination alone had lower levels of Ig anti-RBD, which rapidly waned over time. To restore the waning antibody, a third dose vaccination is recommended for uninfected individuals who have only received 2 doses.

The aim of this study is to investigate the reactogenicity and immunogenicity of the fourth dose using monovalent mRNA vaccines after different three-dose regimens and to compare the 30 µg BNT162b2 and 50 µg mRNA-1273 vaccines. This prospective cohort study was conducted between June and October 2022. The self-recorded reactogenicity was evaluated on the subsequent 7 days after a fourth dose. The binding and neutralizing activity of antibodies against the Omicron BA.4/5 variants were determined. Overall, 292 healthy adults were enrolled and received BNT162b2 or mRNA-1273. Reactogenicity was mild to moderate and well tolerated after a few days. Sixty-five individuals were excluded. Thus, 227 eligible individuals received a fourth booster dose of BNT162b2 (n = 109) and mRNA-1273 (n = 118). Most participants, regardless of the type of previous three-dose regimens, elicited a significantly high level of binding antibodies and neutralizing activity against Omicron BA.4/5 28 days after a fourth dose. The neutralizing activity against Omicron BA.4/5 between the BNT162b2 (82.8%) and mRNA-1273 (84.2%) groups was comparable with a median ratio of 1.02. This study found that the BNT162b2 and mRNA-1273 vaccines can be used as a fourth booster dose for individuals who were previously immunized with any prior three-dose mix-and-match COVID-19 vaccine regimens.