Long-Term Dynamic Changes in Hybrid Immunity over Six Months after Inactivated and Adenoviral Vector Vaccination in Individuals with Previous SARS-CoV-2 Infection.

Numerous studies have largely focused on short-term immunogenicity in recovered individuals post mRNA vaccination. However, understanding the long-term durability, particularly in inactivated and adenoviral vectored vaccines, remains limited. We evaluated antibody responses, omicron variant neutralization, and IFN-γ responses in 119 previously infected individuals vaccinated with CoronaVac or ChAdOx1 up to six months post-vaccination. Both vaccines elicited robust immune responses in recovered individuals, surpassing those who were infection-naïve, and these persisted above pre-vaccination levels for six months. However, antibody levels declined over time (geometric mean ratio (GMR) = 0.52 for both vaccines). Notably, neutralizing activities against omicron declined faster in ChAdOx1 (GMR = 0.6) compared to CoronaVac recipients (GMR = 1.03). While the first dose of ChAdOx1 adequately induced immune responses in recovered individuals, a second dose demonstrated advantages in omicron variant neutralization and slower decline. Although both vaccines induced T cell responses, the median IFN-γ level at six months returned to pre-vaccination levels. However, more individuals exhibited reactive T cell responses. Extending the interval (13-15 months) between infection and vaccination could enhance antibody levels and broaden neutralization. Together, these findings demonstrate a robust humoral and cellular response that was sustained for at least six months after vaccination, thus guiding optimal vaccination strategies based on prior infection and vaccine platforms.

Real-World Study: Hybrid Immunity against SARS-CoV-2 Influences the Antibody Levels and Persistency Lasting More than One Year.

This study investigated the impact of hybrid immunity on antibody responses in the participants who received two to seven doses of the COVID-19 vaccine. The study was conducted between April and June 2023. Out of 771 serum samples analyzed, 71.7% exhibited hybrid immunity (positive for total anti-N Ig), while 28.3% showed vaccine-induced immunity (negative for total anti-N Ig). Participants were categorized based on the number of vaccine doses: 2, 3, 4, and ≥5. The findings highlight a trend where a higher number of vaccine doses received was associated with a lower infection rate. There was no significant difference in total RBD Ig levels between those who received 3, 4, or ≥5 doses in both the hybrid immunity and vaccination alone groups across all observed durations as follows: <6 months, 6 to <9 months, 9 to <12 months, and ≥12 months. Hybrid immunity consistently maintained higher total RBD Ig levels and durability compared to vaccination alone, with estimated half-lives (T1/2) of 189.5 days versus 106.8 days for vaccine alone. This investigation underscored the potential benefit of hybrid immunity and raised questions about the optimal strategies for further vaccine dosing.

Seroprevalence of SARS-CoV-2 anti-nucleocapsid total Ig, anti-RBD IgG antibodies, and infection in Thailand: a cross-sectional survey from October 2022 to January 2023.

Seroprevalence studies on SARS-CoV-2 are essential for estimating actual prevalence rates of infection and vaccination in communities. This study evaluated infection rates based on total anti-nucleocapsid immunoglobulin (N) and/or infection history. We determined the seroprevalence of anti-receptor binding domain (RBD) antibodies across age groups. A cross-sectional study was conducted in Chonburi province, Thailand, between October 2022 and January 2023. Participants included newborns to adults aged up to 80 years. All serum samples were tested for anti-N total Ig and anti-RBD IgG. The interviewer-administered questionnaires queried information on infection history and vaccination records. Of 1459 participants enrolled from the Chonburi population, ~ 72.4% were infected. The number of infections was higher in children aged < 5 years, with evidence of SARS-CoV-2 infection decreasing significantly with increasing age. There were no significant differences based on sex or occupation. Overall, ~ 97.4% of participants had an immune response against SARS-CoV-2. The anti-RBD IgG seroprevalence rate was lower in younger vaccinated individuals and was slightly increased to 100% seropositivity at ages > 60 years. Our findings will help predict the exact number of infections and the seroprevalence of SARS-CoV-2 in the Thai population. Furthermore, this information is essential for public health decision-making and the development of vaccination strategies.

SARS-CoV-2 Antibody Dynamics after COVID-19 Vaccination and Infection: A Real-World Cross-Sectional Analysis.

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.

Evaluation of Anti-S1 IgA Response to Different COVID-19 Vaccination Regimens.

IgA plays a crucial role in early virus neutralization. To identify the IgA stimulation by COVID-19 vaccine, this study aimed to evaluate the level of anti-S1 IgA in the serum of participants immunized with different COVID-19 vaccination regimens. Sera from 567 eligible participants vaccinated with two, three, or four doses of different types of COVID-19 vaccine were recruited. Post-vaccine anti-S1 IgA responses significantly varied according to vaccine type and regimen. The finding showed that heterologous boosters, especially after priming with an inactivated vaccine, elicited higher IgA levels than homologous boosters. Vaccination with SV/SV/PF produced the highest IgA level among all the immunization regimens after either two, three, or four doses. The different routes and amounts of vaccine used for vaccination showed non-significant differences in IgA levels. After the third dose of immunization for 4 months, the level of IgA decreased significantly from the level found on day 28 in both SV/SV/AZ and SV/SV/PF groups. In conclusion, our study showed that heterologous booster regimens for COVID-19 elicited higher anti-S1 IgA levels in serum, especially after priming with inactivated vaccine. The presented anti-S1 IgA may have advantages in preventing SARS-CoV-2 infection and severe disease.

Investigation of the Molecular Epidemiology and Evolution of Circulating Severe Acute Respiratory Syndrome Coronavirus 2 in Thailand from 2020 to 2022 via Next-Generation Sequencing.

Coronavirus disease 2019 (COVID-19) is an infectious condition caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which surfaced in Thailand in early 2020. The current study investigated the SARS-CoV-2 lineages circulating in Thailand and their evolutionary history. Complete genome sequencing of 210 SARS-CoV-2 samples collected from collaborating hospitals and the Institute of Urban Disease Control and Prevention over two years, from December 2020 to July 2022, was performed using next-generation sequencing technology. Multiple lineage introductions were observed before the emergence of the B.1.1.529 omicron variant, including B.1.36.16, B.1.351, B.1.1, B.1.1.7, B.1.524, AY.30, and B.1.617.2. The B.1.1.529 omicron variant was subsequently detected between January 2022 and June 2022. The evolutionary rate for the spike gene of SARS-CoV-2 was estimated to be between 0.87 and 1.71 × 10-3 substitutions per site per year. There was a substantial prevalence of the predominant mutations C25672T (L94F), C25961T (T190I), and G26167T (V259L) in the ORF3a gene during the Thailand outbreaks. Complete genome sequencing can enhance the prediction of future variant changes in viral genomes, which is crucial to ensuring that vaccine strains are protective against worldwide outbreaks.

Comparison of the reactogenicity and immunogenicity between two-dose mRNA COVID-19 vaccine and inactivated COVID-19 vaccine followed by an mRNA vaccine in children aged 5-11 years.

To compare the reactogenicity and immunogenicity between the two-dose mRNA COVID-19 vaccine regimen and one or two doses of inactivated vaccine followed by an mRNA vaccine regimen in healthy children between 5 and 11 years of age, a prospective cohort study was performed at King Chulalongkorn Memorial Hospital in Thailand between March to June 2022. Healthy children between 5 and 11 years of age were enrolled and received the two-dose mRNA COVID-19 vaccine (BNT162b2) regimen or the inactivated (CoronaVac) vaccine followed by the BNT162b2 vaccine regimen. In addition, healthy children who received two doses of BBIBP-CorV between 1 and 3 months prior were enrolled to receive a heterologous BNT162b2 as a third dose (booster). Reactogenicity was assessed by a self-reported online questionnaire. Immunogenicity analysis was performed to determine binding antibodies to wild-type SARS-CoV-2. Neutralizing antibodies to Omicron variants (BA.2 and BA.5) were tested using the focus reduction neutralization test. Overall, 166 eligible children were enrolled. Local and systemic adverse events which occurred within 7 days after vaccination were mild to moderate and well-tolerated. The two-dose BNT162b2, CoronaVac followed by BNT162b2, and two-dose BBIBP-CorV followed by BNT162b2 groups elicited similar levels of anti-receptor-binding domain (RBD) IgG. However, the two-dose BNT162b2 and two-dose BBIBP-CorV followed by BNT162b2 groups elicited higher neutralizing activities against the Omicron BA.2 and BA.5 variant than the CoronaVac followed by BNT162b2 group. The CoronaVac followed by BNT162b2 group elicited low neutralizing activities against the Omicron BA.2 and BA.5 variant. A third dose (booster) mRNA vaccine should be prioritized for this group.

Seroprevalence of anti-SARS-CoV-2 antibodies and associated factors among household contacts of COVID-19 confirmed cases in Bangkok, Thailand.

Background: High COVID-19 transmission among household (HH) contacts of infected cases were reported with seroprevalence varying from 5.5% to 57.2% worldwide. Data on seroprevalence among HH contacts and factors associated with seropositivity in Thailand are limited. Objectives: To determine the seroprevalence and factors associated with anti-SARS-CoV-2 antibodies among HH contacts of COVID-19 confirmed cases. Materials and methods: Data on confirmed COVID-19 cases (primary cases) in Bangkok from March 2020-July 2021 were retrieved from Institute for Urban Disease Control and Prevention. Primary cases were contacted within 14 days of testing positive for permission to contact their HH contacts via telephone. HH contacts were then recruited to complete questionnaires about demographics, and risk factors and blood was collected and tested for total immunoglobulin antibody against SARS-CoV-2 spike S1 protein. Factors associated with seropositivity were analysed by logistic regression. Results: Eligible participants of 452 HH contacts of infected cases in Bangkok were contacted. Seroprevalence was 20.5% among HH contacts. Factors associated with seropositivity after multivariate analysis were relationship to index case (being other relatives to index case (other than close relatives/spouse) [aOR 4.04, 95% CI; 1.15, 14.14, p.029] and being a co-worker to index cases [aOR 0.16, 95% CI; 0.045, 0.60, p.006]), always staying in the same room with index case [aOR 5.64, 95% CI; 1.95, 16.34, p.001], sharing utensil [aOR 0.25, 95% CI; 0.074, 0.82, p.023], and participation in leisure activities together with index case [aOR 4.77, 95% CI; 1.47, 15.51, p.009]. Conclusion: Serological investigation can be used in detecting COVID-19 infection in conjunction with other molecular techniques. It is a useful tool for studies on seroprevalence in a population as well as seroconversion after a vaccination campaign. Sharing living environments are associated with seropositivity in HH contacts. Nevertheless, individual practices can be affected by awareness, cultural differences, and control measures implemented by each country.

The Fourth Dose of mRNA COVID-19 Vaccine Following 12 Different Three-Dose Regimens: Safety and Immunogenicity to Omicron BA.4/BA.5.

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.

Molecular characterisation and tracking of severe acute respiratory syndrome coronavirus 2 in Thailand, 2020-2022.

The global COVID-19 pandemic, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first detected in China in December 2019. To date, there have been approximately 3.4 million reported cases of COVID-19 and over 24,000 deaths in Thailand. In this study, we investigated the molecular characteristics and evolution of SARS-CoV-2 in Thailand from 2020 to 2022. Two hundred sixty-eight SARS-CoV-2 isolates, collected mostly in Bangkok from COVID-19 patients, were characterised by partial genome sequencing. Moreover, the viruses in 5,627 positive SARS-CoV-2 samples were identified as viral variants - B.1.1.7 (Alpha), B.1.617.2 (Delta), B.1.1.529 (Omicron/BA.1), or B.1.1.529 (Omicron/BA.2) - by multiplex real-time reverse transcription polymerase chain reaction (RT-PCR) assays. The results revealed that B.1.36.16 caused the predominant outbreak in the second wave (December 2020-January 2021), B.1.1.7 (Alpha) in the third wave (April-June 2021), B.1.617.2 (Delta) in the fourth wave (July-December 2021), and B.1.1.529 (Omicron) in the fifth wave (January-March 2022). The evolutionary rate of the viral genome was 2.60 × 10-3 (95% highest posterior density [HPD], 1.72 × 10-3 to 3.62 × 10-3) nucleotide substitutions per site per year. Continued molecular surveillance of SARS-CoV-2 is crucial for monitoring emerging variants with the potential to cause new COVID-19 outbreaks.

Safety and immunogenicity of a third dose of COVID-19 protein subunit vaccine (CovovaxTM) after homologous and heterologous two-dose regimens.

OBJECTIVES: To report the safety and immunogenicity profile of a protein subunit vaccine (CovovaxTM) given as a third (booster) dose to individuals primed with different primary vaccine regimens. METHODS: A third dose was administered to individuals with an interval range of 3-10 months after the second dose. The four groups were classified according to their primary vaccine regimens, including two-dose BBIBP-CorV, AZD1222, BNT162b2, and CoronaVac/AZD1222. Immunogenicity analysis was performed to determine binding antibodies, neutralizing activity, and the T-cell responses. RESULTS: Overall, 210 individuals were enrolled and boosted with the CovovaxTM vaccine. The reactogenicity was mild to moderate. Most participants elicited a high level of binding and neutralizing antibody against Wild-type and Omicron variants after the booster dose. In participants who were antinucleocapsid immunoglobulin G-negative from all groups, a booster dose could elicit neutralizing activity to Wild-type and Omicron variants by more than 95% and 70% inhibition at 28 days, respectively. The CovovaxTM vaccine could elicit a cell-mediated immune response. CONCLUSION: The protein subunit vaccine (CovovaxTM) can be proposed as a booster dose after two different priming dose regimens. It has strong immunogenicity and good safety profiles.

Comparison of the reactogenicity and immunogenicity of a reduced and standard booster dose of the mRNA COVID-19 vaccine in healthy adults after two doses of inactivated vaccine.

The coronavirus disease 2019 (COVID-19) pandemic has been a serious healthcare problem worldwide since December 2019. The third dose of heterologous vaccine was recently approved by World Health Organization. The present study compared the reactogenicity and immunogenicity of the reduced and standard third booster dose of the BNT162b2 and mRNA-1273 vaccine in adults who previously received the two-dose CoronaVac vaccine. Results showed that headache, joint pain, and diarrhea were more frequent in the 15 µg- than the 30 µg-BNT162b2 groups, whereas joint pain and chilling were more frequent in the 100 µg- than the 50 µg-mRNA-1273 groups. No significant differences in immunogenicity were detected. These findings demonstrate that the reduced dose of the mRNA vaccines elicited antibody responses against the SARS-CoV-2 delta and omicron variants that were comparable to the standard dose. The reduced dose could be used to increase vaccine coverage in situations of limited global vaccine supply.

Immunogenicity of ChAdOx1-nCoV-19 vaccine in solid malignancy patients by treatment regimen versus healthy controls: A prospective, multicenter observational study.

Background: Limited data exists regarding the efficacy of ChAdOx1-nCoV-19 vaccine against Severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) in solid cancer patients. We aimed to assess the immunogenicity of the ChAdOx1-nCoV-19 vaccine and the impact of different anticancer therapies for solid malignancies on immune response. Methods: This prospective, longitudinal observational study of immunogenicity following ChAdOx1-nCoV-19 vaccination among 385 solid cancer patients on active cancer treatment was conducted in two oncology centers. Participants received the first dose between June 18 and July 27, 2021 and the second dose at 8-10 weeks later. Blood samples were evaluated for total immunoglobulins against the receptor-binding of SARS-CoV-2 spike protein (anti-RBD total-Ig) before, and 4-week after the first- and second-doses. The primary endpoint was the geometric mean titers (GMT) of antibody among solid cancer patients compared to healthy controls and the impact of different cancer treatment types. Findings: Among solid cancer patients, the antibody level increased more slowly to significantly lower levels than achieved in healthy controls. The GMT at 4-weeks post-vaccination in cancer vs. healthy were 224.5 U/ml (95%CI 176.4-285.6) vs. 877.1 U/ml (95%CI 763.5-1008), p<0.0001), respectively. For different types of cancer treatments, chemotherapy agents, especially anthracyclines (GMR 0.004; 95%CI 0.002-0.008), paclitaxel (GMR 0.268; 95%CI 0.123-0.581), oxaliplatin (GMR 0.340; 95%CI 0.165-0.484), and immunotherapy (GMR 0.203; 95%CI 0.109-0.381) showed significantly lower antibody response. Anti-HER2, endocrine therapy and 5-fluouracil or gemcitabine, however, had less impact on the immune response. Interpretation: Suboptimal and heterogeneous immunologic responses were observed in cancer patients being treated with different systemic treatments. Immunotherapy or chemotherapy significantly suppressed the antibody response. Funding: Quality Improvement Fund, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society and Center of Excellence in Clinical Virology at Chulalongkorn University and Chulalongkorn Medical Oncology Research Fund.

Vaccine-Related adverse events following AZD1222 (ChAdOx1-nCoV-19) Covid-19 vaccine in solid malignancy patients receiving cancer treatment, as compared to age-matched healthy controls.

The study aimed to evaluate vaccine-related adverse events (VRAEs) following ChAdOx1-nCoV-19 vaccine in solid cancer patients receiving treatment compared to healthy controls. 399 cancer patients and 90 healthy volunteers were enrolled. In the overall population, the incidence of VRAEs was significantly lower in cancer patients than in healthy volunteers (57% vs 80%, P < .001). Because the mean age of the cancer patients was higher than the healthy volunteers (59 vs 48 years, P < .001), we analyzed age-matched comparison and found that there was no significant difference of VRAEs between two groups (74% vs 79%, P .32). Most VRAEs were of mild severity in both groups. The most common local VRAE was pain at the injection site in both groups, and the most common systemic VRAE was fatigue in the cancer cohort, while myalgia was the most common VRAE among the healthy controls. In the cancer cohort, fever was the only VRAE that led to interruption of the cancer treatment (in two cases). Among the cancer treatment types, patients undergoing chemotherapy-containing regimens had a lower likelihood of experiencing VRAEs. In summary, the overall incidence of VRAEs following ChAdOx1-nCoV-19 vaccine in actively treated cancer patients was comparable to healthy controls after adjusting for age. The VRAEs that occurred rarely interfered with the cancer treatment. These findings substantiate that vaccination with AZD1222 is safe in cancer patients undergoing treatment.

Strong Correlations between the Binding Antibodies against Wild-Type and Neutralizing Antibodies against Omicron BA.1 and BA.2 Variants of SARS-CoV-2 in Individuals Following Booster (Third-Dose) Vaccination.

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.

Immunogenicity Following Two Doses of the BBIBP-CorV Vaccine and a Third Booster Dose with a Viral Vector and mRNA COVID-19 Vaccines against Delta and Omicron Variants in Prime Immunized Adults with Two Doses of the BBIBP-CorV Vaccine.

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-É£ 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.

Immunogenicity of heterologous inactivated and adenoviral-vectored COVID-19 vaccine: Real-world data.

Limited data are available on the responses to heterologous vaccine regimens for SARS-CoV-2, especially among countries using inactivated and adenoviral-vectored vaccines. A total of 77 participants who received heterologous inactivated COVID-19 vaccine (CoronaVac) and adenoviral-vectored vaccine (AZD1222) were enrolled in our study. There were two comparison groups vaccinated with the homologous CoronaVac (N = 79) and AZD1222 (N = 78) regimen. All sera samples were tested for anti-receptor-binding-domain IgG (anti-RBD IgG) using a chemiluminescent microparticle immunoassay (CMIA). The neutralizing activity in a subset of serum samples was tested against the original Wuhan strain and variants of concern, B.1.1.7, B.1.617.2 and B.1.351, using an enzyme-linked immunosorbent assay (ELISA)-based surrogate virus neutralization test (sVNT). The heterologous CoronaVac/AZD1222 vaccine induced higher levels of anti-RBD IgG than that of two-dose homologous CoronaVac or AZD1222 vaccines (p < 0.001). Sera samples of the CoronaVac/AZD1222 vaccine recipients elicited higher neutralizing antibody activity against the original Wuhan and all variants of concern than in the recipients of the two-dose CoronaVac. The heterologous CoronaVac followed by AZD1222 is an alternative regimen to combat with the SARS-CoV-2 variants in case of vaccine shortage with improved immunogenicity compared to the homologous CoronaVac regimen.