SARS-CoV-2 infection- induced seroprevalence among children and associated risk factors during pre- and omicron-dominant wave, from January 2021 through November 2022, Thailand: Longitudinal study

BackgroundSevere acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection can be asymptomatic in young children. Therefore, the true rate of infection is likely underestimated. Few data are available on the rate of infections in young children, and studies on the SARS-CoV-2 seroprevalence among children during omicron wave are limited. Our study aims to assess the SARS-CoV-2 infection-induced seroprevalence among children and estimated the associated risk factors for seropositivity. MethodsA longitudinal serological survey was conducted from January 2021 through November 2022. Samples were tested for anti-nucleocapsid (N) IgG, anti-receptor binding domain (RBD) IgG using a chemiluminescent microparticle immunoassay (CMIA) and detected anti-RBD Immunoglobulin (Ig) using an electrochemiluminescence immunoassay (ECLIA). The vaccination and SARS-CoV-2 infection history were collected. ResultsA total of 452 serum samples were obtained from 249 children aged 5-7 years old who were annually followed-up in the longitudinal serological survey. Of these, 191 participants provided samples at two serial time points, including during the pre-and omicron dominant wave. Overall, seroprevalence induced by SARS-CoV-2 infection was increased from 9.1% (95%CI: 0.6-12.6%) during the pre-omicron wave to 49.7% (95%CI: 35.9-66.8%) during the omicron wave. Amongst seropositive individuals, the infection-induced seroprevalence was lower in vaccinated participants than those with no vaccination (40.4% vs. 57.4%; risk ratio, 0.71; 95%CI: 0.52-0.95). Nevertheless, the ratio of seropositive cases per recalled infection was 1.56 during the omicron dominant wave. In addition, overall seroprevalence induced by infection, vaccination and hybrid immunity was 76.6% (151/197; 95%CI: 54.6-97.9%) between January and November 2022. Conclusionsour study reports an increase in infection-induced seroprevalence among children during the omicron wave. These findings highlight that estimating seroprevalence is crucial to monitor SARS-CoV-2 exposure, particularly in asymptomatic infection, and help to optimize public health policies and determine the effect of immunization in the pediatric population.

Immunogenicity and durability against Omicron BA.1, BA.2 and BA.4/5 variants at 3 to 4 months after a heterologous COVID-19 booster vaccine in healthy adults with a two-doses CoronaVac vaccination

ObjectivesSeveral countries have authorized a booster vaccine campaign to combat the spread of COVID-19. Data on persistence of booster vaccine-induced immunity against new Omicron subvariants are still limited. Therefore, our study aimed to determine the serological immune response of COVID-19 booster after CoronaVac-priming. MethodsA total of 187 CoronaVac-primed participants were enrolled and received an inactivated (BBIBP), viral vector (AZD1222) or mRNA vaccine (full-/half-dose BNT162B2, full-/half-dose mRNA-1273) as a booster dose. The persistence of humoral immunity both binding and neutralizing antibodies against wild-type and Omicron was determined on day 90- 120 after booster. ResultsA waning of total RBD immunoglobulin (Ig) levels, anti-RBD IgG, and neutralizing antibodies against Omicron BA.1, BA.2, and BA.4/5 variants was observed 90-120 days after booster vaccination. Participants who received mRNA-1273 had the highest persistence of the immunogenicity response, followed by BNT162b2, AZD1222, and BBIBP-CorV. The responses between full and half doses of mRNA-1273 were comparable. The percentage reduction of binding antibody ranged from 50% to 75% among all booster vaccine. ConclusionsThe antibody response substantially waned after 90-120 days post-booster dose. The heterologous mRNA and the viral vector booster demonstrated higher detectable rate of humoral immune responses against the Omicron variant compared to the inactivated BBIBP booster. Nevertheless, an additional fourth dose is recommended to maintain immune response against infection. HighlightsO_LIThe persistence of antibody responses is different among three vaccine platforms. C_LIO_LIHighly remained antibody levels were observed with the mRNA and viral vector booster. C_LIO_LIThe half-dose mRNA-1273 can be used interchangeably with the full-dose mRNA-1273. C_LIO_LIThe neutralizing activity against BA.5 was lower than wild type and BA.2 subvariant. C_LIO_LIA fourth dose is recommended for individuals who received an inactivated booster. C_LI

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

ObjectiveTo 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 5-11 years of age. MethodsA prospective cohort study was performed at King Chulalongkorn Memorial Hospital in Thailand between March to June 2022. Healthy children between 5-11 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 1-3 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 and surrogate neutralizing antibodies to SARS-CoV-2 wild-type and Omicron variants. ResultsOverall, 166 eligible children were enrolled. Local and systemic AE which occurred within 7 days after vaccination were mild to moderate and well-tolerated. At one-month, post-two or post-three doses, children vaccinated with two-dose BNT162b2, CoronaVac/BNT162b2, and two-dose BBIBP-CorV followed by BNT162b2 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 Omicron BA.2 variant than the CoronaVac/BNT162b2 group. ConclusionThe heterologous, CoronaVac vaccine followed by the BNT162b2 vaccine, regimen elicited lower neutralizing activities against the emerging Omicron BA.2 variant than the two-dose mRNA regimen. A third dose (booster) mRNA vaccine should be prioritized for this group.

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

ObjectiveTo report the safety and immunogenicity profile of a protein subunit vaccine (Covovax) given as a third (booster) dose to individuals primed with different primary vaccine regimens. MethodsIndividuals primed with two doses of COVID-19 vaccines for at least 3 months were enrolled and assigned to five groups according to their primary vaccine regimens: CoronaVac, BBIBP-CorV, AZD1222, BNT162b2, and CoronaVac/AZD1222. Immunogenicity analysis was performed to determine binding antibodies, neutralizing activity, and the T-cell response. ResultsOverall, 215 individuals were enrolled and boosted with the Covovax vaccine. The reactogenicity achieved was mild-to-moderate. Most participants elicited a high level of binding and neutralizing antibody responses against wild type and omicron variants following the booster dose. The 197 participants were classified by anti-N IgG. Of these, 141/197 (71.6%) were a seronegative population, and neutralizing activity and IFN-{gamma} release were further monitored. 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 Covovax vaccine could elicit a cell-mediated immune response. ConclusionThe protein subunit vaccine (Covovax) can be proposed as a booster dose after two different priming dose regimens. It has strong immunogenicity and good safety profiles.

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 SARS-CoV-2 RBD antibody 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) vaccination 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 with [≥]148 BAU/mL and [≥]138 BAU/mL were related to detectable FRNT50 titers ([≥]1:20) against BA.1 and BA.2, respectively. A moderate correlation was observed between the sVNT and FRNT50 titers. At detectable FRNT50 titers ([≥]1:20), the predicted sVNT for BA.1 and BA.2 were [≥]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 BBIBP-CorV vaccine and a third booster dose with viral vector and mRNA COVID-19 vaccines against delta and omicron variants in prime immunized adults with two doses of 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 BBIBP-CorV vaccine and to explore the boosting effect of the different vaccine platforms in BBIBP-CorV-primed healthy adults, including 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) immuno-globulin (Ig) and anti-RBD IgG levels waned significantly at 3 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 of inhibition over 90% against the SARS-CoV-2 delta variant but less than 70% against omicron variant after the third dose on day 28. All booster vaccines could induce the total IFN-{square} T-cell response. The reactogenicity was acceptable and well tolerated without serious adverse events. This study supported administration of the third dose with either viral vector or mRNA vaccine for the BBIBP-CorV-primed individuals to stimulate antibody and T cell responses.

Persistence of immunity against omicron BA.1 and BA.2 following homologous and heterologous COVID-19 booster vaccines in healthy adults after a two-doses AZD1222 vaccination

ObjectivesThe SARS-CoV-2 Omicron variant presents numerous mutations potentially able to evade neutralizing antibodies (NAbs) elicited by COVID-19 vaccines. Therefore, this study aimed to provide evidence on a heterologous booster strategy to overcome the waning immunity against Omicron variants. MethodsParticipants who completed Oxford/AstraZeneca (hereafter AZD1222) for 5-7 months were enrolled. The reactogenicity and persistence of immunogenicity in both humoral and cellular response after a homologous or heterologous booster with the AZD1222 and mRNA vaccines (BNT162B2, full or half-dose mRNA-1273) administered six months after primary vaccination were determined. ResultsTotal 229 individuals enrolled, a waning of immunity was observed 5-7 months after the AZD1222-primed. Total RBD immunoglobulin (Ig) levels, anti-RBD IgG and focus reduction neutralization test against Omicron BA.1 and BA.2 and T cell response peaked 14-28 days after booster vaccination. Both the full and half dose of mRNA-1273 induced the highest response, followed by BNT162b2 and AZD1222. At 90 days, the persistence of immunogenicity was observed among all mRNA-boosted individuals. Adverse events were acceptable and well tolerated for all vaccines. ConclusionsA heterologous mRNA booster provided a significantly superior boost of binding and NAbs levels against the Omicron variant compared to a homologous booster in individuals with AZD1222-primed vaccinations.

Effects of boosted mRNA and adenoviral-vectored vaccines on immune responses to omicron BA.1 and BA.2 following the heterologous CoronaVac/AZD1222 vaccination

BackgroundThe coronavirus 2019 omicron variant has surged rapidly and raises concerns about immune evasion because it harbors mutations even in individuals with complete vaccination. Here, we examine the capability of the booster vaccination to induce neutralizing antibodies (NAbs) against omicron (BA.1 and BA.2) and T-cell responses. MethodsA total of 167 participants primed with heterologous CoronaVac/AZD1222 were enrolled to receive AZD1222, BNT162b2, or mRNA-1273 as a booster dose. Reactogenicity was recorded. Binding antibody, neutralizing antibody (NAb) titers against omicron BA.1 and BA.2, and total interferon gamma (IFN-{gamma}) post-booster responses were measured. ResultsA substantial loss in neutralizing potency to omicron variant was found at 4 to 5 months after receiving the heterologous CoronaVac/AZD1222. Following booster vaccination, a significant increase in binding antibodies and neutralizing activities toward delta and omicron variants was observed. Neutralization to omicron BA.1 and BA.2 were comparable, showing the highest titers after boosted mRNA-1273 followed by BNT162b2 and AZD1222. Notably, boosted individuals with mRNA vaccines could induce T cell response. Reactogenicity was mild to moderate without serious adverse events. ConclusionsOur findings highlight that the booster vaccination could overcome immunity wanes and provide adequate NAbs coverage against omicron BA.1 and BA.2.

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 g-than the 30 g-BNT162b2 groups, whereas joint pain and chilling were more frequent in the 100 g-than the 50 g-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. HighlightsO_LIThe 15 g- and 30 g-BNT162b2, and 50 g- and 100 g-mRNA-1273 booster doses were compared C_LIO_LIBooster vaccination with the mRNA vaccine elicits high Ig and IgG anti-RBD in CoronaVac-vaccinated adults C_LIO_LINo differences were observed in antibody responses after the reduced or standard booster dose of the mRNA vaccine in CoronaVac-vaccinated adults C_LIO_LINeutralizing antibodies against the delta and omicron variants were significantly higher after the booster dose C_LIO_LINeutralizing antibody titers were lower against the omicron variant than the delta variant in all vaccinated adults C_LI

Neutralizing Activities against the Omicron Variant after a Heterologous Booster in Healthy Adults Receiving Two Doses of CoronaVac Vaccination

BackgroundThe use of an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (CoronaVac) against SARS-CoV-2 is implemented worldwide. However, waning immunity and breakthrough infections have been observed. Therefore, we hypothesized that the heterologous booster might improve the protection against the delta and omicron variants. MethodsA total of 224 individuals who completed the two-dose CoronaVac for six months were included. We studied reactogenicity and immunogenicity following a heterologous booster with the inactivated vaccine (BBIBP), the viral vector vaccine (AZD1222), and the mRNA vaccine (both BNT162B2 and mRNA-1273). We also determined immunogenicity at 3- and 6-months boosting intervals. ResultsThe solicited adverse events (AEs) were mild to moderate and well-tolerated. Total RBD immunoglobulin (Ig), anti-RBD IgG, focus reduction neutralization test (FRNT50) against delta and omicron variants, and T cell response were highest in the mRNA-1273 group followed by the BNT162b2, AZD1222 and BBIBP groups, respectively. We also witnessed a higher total Ig anti-RBD in the long-interval than in the short-interval groups. ConclusionsAll four booster vaccines significantly increased binding and NAbs in individuals immunized with two doses of CoronaVac. The present evidence may benefit vaccine strategies development to thwart variants of concern, including the omicron variant.

COVID-19 breakthrough infection after inactivated vaccine induced robust antibody responses and cross-neutralization of SARS-CoV-2 variants, but less immunity against omicron

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 = 78), 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 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 activities are exceeding 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 antibody against omicron. Further investigation is needed to assess the long-term persistence of antibody against omicron variant.

Immune responses to inactivated and vector-based vaccines in individuals previously infected with SARS-CoV-2

Immunity wanes in individuals previously infected with SARS-CoV-2, and vaccinating those individuals may help reduce reinfection. Herein, reactogenicity and immunogenicity following vaccination with inactivated (CoronaVac) and vector-based (ChAdOx1-S, AZD1222) vaccines were examined in previously infected individuals. Immune response was also compared between short and long intervals between first date of detection and vaccination. Adverse events were mild but were higher with AZD1222 than with CoronaVac. Baseline IgG-specific antibodies and neutralizing activity were significantly higher with shorter than longer intervals. With a single-dose vaccine, IgG and IgA-specific binding antibodies, neutralizing activity, and total interferon-gamma response peaked at 14 days. Immune response was significantly higher in recovered individuals than in infection-naive individuals. Antibody response was greater with longer than shorter intervals. AZD1222 induced higher antibody and T cell responses than those of CoronaVac. Thus, to achieve immunity, individuals with prior SARS-CoV-2 exposure may require only a single dose of AZD1222 or two doses of CoronaVac to achieve the immune response. These findings supported vaccine strategies in previously infected individuals.

Safety and immunogenicity of the third booster dose with inactivated, viral vector, and mRNA COVID-19 vaccines in fully immunized healthy adults with inactivated vaccine

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 interferon gamma-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.

Safety and immunogenicity of heterologous and homologous inactivated and adenoviral-vectored COVID-19 vaccines in healthy adults

In light of intermittent supply shortages of individual vaccines and evidence of rare but serious adverse events after vaccination, heterologous regimens for COVID-19 vaccines have gained significant interest. This study aims to assess the reactogenicity and immunogenicity of the heterologous adenoviral vector vaccine regimen (ChAdOx1-S, AstraZeneca; hereafter referred to as AZ) and the inactivated vaccine regimen (CoronaVac; hereafter referred to as CV) regimen in healthy Thai adults immunized between June and September 2021. Our study showed that adverse events following homologous CV-CV and AZ-AZ, and heterologous CV-AZ and AZ-CV combinations, were mild and well tolerated overall. Receptor-binding domain (RBD)-specific antibody responses and neutralizing activities against wild-type and variants of concern after two-dose vaccination were higher in the heterologous CV-AZ and homologous AZ-AZ groups compared to the CV-CV and AZ-CV groups. Conversely, the spike-specific IgA response was detected only in the CV-AZ group after two doses of vaccination. The total interferon gamma response was detected in both the CV-AZ and AZ-CV groups after the two-dose vaccination. Given the shorter completion time of two doses, heterologous CoronaVac followed by ChAdOx1-S can be considered as an alternative regimen to homologous efficacy-proven ChAdOx1-S in countries with circulating variants. Additional studies on the efficacy and durability of immune responses induced by heterologous vaccine regimens are warranted.

Immunogenicity of a third dose viral-vectored COVID-19 vaccine after receiving two-dose inactivated vaccines in healthy adults

In June 2021, Thailand was hit by the delta variant of SARS-CoV-2 resulting in the biggest wave of COVID-19. Due to the widespread delta variant, more than 600 healthcare workers had COVID-19 despite completion of two-dose CoronaVac. The Ministry of Public Health recommended that healthcare workers received a third dose of AZD1222 to increase level of protection against SARS-CoV-2. However, immune response after the third vaccination with AZD1222 are limited. In this study, sera from those who received a booster of AZD1222 in June-July 2021 were tested for SARS-CoV-2 spike receptor-binding-domain (RBD) IgG, anti-RBD total immunoglobulins and anti-spike protein 1 (S1) IgA. The neutralizing activities in a subset of serum samples were tested against the wild type and variants of concern (B.1.1.7, B.1.617.2, and B.1.351) using an enzyme-linked immunosorbent assay-based surrogate virus neutralization test. Participants who received the booster of AZD1222 possessed higher levels of spike RBD-specific IgG, total immunoglobulins, and anti-S1 IgA than that two-dose vaccines (p < 0.001). They also elicited higher neutralizing activity against the wild type and all variants of concern than those in the recipients of the two-dose vaccines. This study demonstrated a high immunogenicity of the AZD1222 booster who completed the two-dose inactivated vaccines.