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.

Neutralizing Activities Against the Omicron Variant After a Heterologous Booster in Healthy Adults Receiving Two Doses of CoronaVac Vaccination.

BACKGROUND: The 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. METHODS: A total of 224 individuals who completed the 2-dose CoronaVac for 6 months were included. We studied reactogenicity and immunogenicity after a heterologous booster with the inactivated vaccine (BBIBP), the viral vector vaccine (AZD1222), and the messenger ribonucleic acid (mRNA) vaccine (both BNT162B2 and mRNA-1273). We also determined immunogenicity at 3- and 6-month boosting intervals. RESULTS: The solicited adverse events were mild to moderate and well tolerated. Total receptor binding domain (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 group. CONCLUSIONS: All 4 booster vaccines significantly increased binding and neutralizing antibodies in individuals immunized with 2 doses of CoronaVac. The present evidence may benefit vaccine strategies to thwart variants of concern, including the omicron variant.

Safety and immunogenicity of inactivated COVID-19 vaccine in health care workers.

Effective vaccines are essential for controlling the coronavirus disease 2019 (COVID-19) pandemic. CoronaVac, which is an inactivated virus vaccine, was the first imported COVID-19 vaccine in Thailand. To investigate the safety and immunogenicity of CoronaVac within the Thai population, we conducted a prospective cohort study among health care workers aged 18-59 years, who received a 2-dose regimen of CoronaVac 21 days apart between March and April 2021 at the hospital in Samut Sakhon, Thailand. We recruited 185 participants with a mean age of 32 years. Total antibodies against receptor-binding domain (RBD) and immunoglobulin G (IgG) against nucleocapsid (N) protein of SARS-CoV-2 were tested. Total antibodies against RBD were negative before immunization. One volunteer was positive for N, although negative for the RBD antibodies. The seroconversion rate of total antibodies against RBD after the first CoronaVac dose was 67% with a Geometric mean concentration (GMC) of 1.98 U/ml. Following CoronaVac dose 2, the seroconversion rate increased to 100% with a GMC of 92.9 U/ml. The seroconversion rates of IgG against N protein were 1% after dose 1 and 62.8% after dose 2. The overall incidence of adverse reactions was 59.5%. Injection-site pain was the most common local adverse event (52.4%), while myalgia was the most common systemic adverse event (31.9%). No serious adverse events were observed. A 0-21 days, 2-dose CoronaVac regimen appears safe, inducing a satisfactory response compared with convalescent serum obtained 4-6 weeks postnatural infection. Antibody responses after 2-dose CoronaVac were comparable to the convalescent plasma but waned rapidly after 3 months. Therefore, we recommend 2-dose CoronaVac administration with possible booster doses.

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

The coronavirus 2019 omicron variant has surged rapidly and raises concerns about immune evasion even in individuals with complete vaccination, because it harbors mutations. Here we examine the capability of booster vaccination following CoronaVac/AZD1222 prime to induce neutralizing antibodies (NAbs) against omicron (BA.1 and BA.2) and T-cell responses. A total of 167 participants primed with heterologous CoronaVac/AZD1222 for 4-5 months were enrolled, to receive AZD1222, BNT162b2, or mRNA-1273 as a third dose. Reactogenicity was recorded. Immunogenicity analyses of severe acute respiratory syndrome coronavirus 2-binding antibodies were measured using enzyme-linked immunosorbent assay. The NAb titers against omicron BA.1 and BA.2 were determined using the focus reduction neutralization test (FRNT50) and total interferon-γ responses were measured to observe the T-cell activation. A substantial loss in neutralizing potency to omicron variant was found at 4-5 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. In addition, individuals boosted with messenger RNA (mRNA) vaccines develop a T-cell response to spike protein, whereas those boosted with AZD1222 did not. Reactogenicity was mild to moderate without serious adverse events. Our findings demonstrated that mRNA booster vaccination is able to overcome waning immunity to provide antibodies that neutralize omicron BA.1 and BA.2, as well as a T-cell response.

Antibody persistence of standard versus double three-dose hepatitis B vaccine in liver transplant children: a randomized controlled trial.

Rapid hepatitis B (HB) surface antibody (anti-HBs) loss is prevalent after liver transplantation (LT). Herein, we evaluated anti-HBs persistence after HB vaccination using two regimens in LT children. We recruited 66 previously immunized LT children with anti-HBs level of < 100 mIU/mL. Participants were randomly reimmunized with standard-three-dose (SD) and double-three-dose (DD) intramuscular HB vaccination at 0, 1, and 6 months. Anti-HBs were assessed at every outpatient visit. Antibody loss defined as anti-HBs levels < 100 mIU/mL after three-dose vaccination. After three-dose vaccination, 81.8% and 78.7% of participants in the SD and DD groups, had anti-HBs levels > 100 mIU/mL, with a geometric mean titer (GMT) of 601.68 and 668.01 mIU/mL (P = 0.983). After a mean follow-up of 2.31 years, the anti-HBs GMT was 209.81 and 212.61 mIU/mL in the SD and DD groups (P = 0.969). The number of immunosuppressants used and an anti-HBs level < 1 mIU/mL at baseline were independently associated with anti-HB loss. The DD regimen strongly increased the risk of anti-HBs loss (adjusted hazard ratio, 2.97 [1.21-7.31]; P = 0.018). The SD HB reimmunization regimen effectively maintained protective anti-HBs levels in children undergoing LT, making it the preferred regimen for such children with anti-HB loss.Trial registration: TCTR20180723002.

Human Enterovirus B Is a Significant Cause of Aseptic Meningitis and Sepsis-Like Illness in Young Infants in Thailand.

Human enterovirus (EV) and Parechovirus (PeV) infections are major causes of sepsis-like illness in infants < 90 days of age. Enterovirus species B (EV-B) was found to be the leading cause of aseptic meningitis in young infants. In Thailand, EV and PeV are not part of the routine screening of blood or cerebrospinal fluid (CSF) of children with suspected aseptic meningitis and sepsis-like illness. Consequently, data on EV and PeV epidemiology are limited. This study tested clinical samples from hospitalized young infants with suspected aseptic meningitis or sepsis-like illness between 2013 and 2022 for EV, PeV, and Herpes simplex virus (HSV). Of 95 specimens, 10 were positive for EV, representing 10.5%. These positive samples included eight CSF and two stool samples. No samples were positive for PeV and HSV. Of these positive cases, EV-B was detected in eight, and EV-A was detected in two cases. The species of EV-B detected include echovirus-18 (E18) (n=2), E21 (n=2), E4(n=1), E5 (n=1), E9 (n=1), and E11 (n=1). Our report demonstrates the significant role of EV-B, and less frequently EV-A, in Thai infants with aseptic meningitis and sepsis-like illness.

Effectiveness of HPV vaccine as part of national immunization program for preventing HPV infection in Thai schoolgirls after seven years post-vaccination.

Thailand introduced a two-dose regimen of bivalent HPV vaccines for Grade 5 schoolgirls, approximately 11 years old, initially piloted in Ayutthaya province in 2014, and nationwide under the National Immunization Program (NIP) in 2017. This cross-sectional, case-control study evaluated the vaccine effectiveness in schoolgirls 7 years after a two-dose administration. Between May and June 2023, 211 grade 12 female students from Ayutthaya, who received the two-dose bivalent HPV vaccine CERVARIXⓇ (HPV types 16 and 18), and 376 grade 12 students from Nakhon Pathom who did not receive the HPV vaccine, were enrolled. HPV infection was detected by testing for HPV DNA in the first-void urine samples using real-time PCR (Cobas® 4800 and AnyplexTM HPV28). The study found that the HPV vaccine 100% effective against high-risk HPV (HR-HPV) types included in the vaccine (16, 18) and 32.8% effective against other HR-HPV types not included in the vaccine. Our findings indicated that the bivalent HPV vaccine does not provide cross-protection against non-vaccine HPV types. Prioritizing vaccines with the highest coverage of HR-HPV types, such as the nonavalent HPV vaccine, is crucial to effectively prevent a broader range of HR-HPV infections under the NIP.

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

Background: Several 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. Methods: A 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. Results: A 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. Conclusions: The 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.

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.

Safety and antibody responses of Omicron BA.4/5 bivalent booster vaccine among hybrid immunity with diverse vaccination histories: A cohort study.

This cohort study, conducted between July and August 2023, evaluated the adverse events (AEs) and immune response to a bivalent mRNA-1273.222 (containing sequences of the original Wuhan-H1 strain and the Omicron BA.4/5 variant) booster vaccine in 122 participants. The study included individuals with diverse vaccination histories, and their responses were assessed based on anti-receptor binding domain (RBD) IgG levels and neutralizing antibodies against the wild-type, Omicron BA.5, and XBB.1.16 variants. Following administration of the BA.4/5 bivalent vaccine, AEs were generally mild to moderate and well-tolerated within a few days. There were no reports of vomiting and no serious AEs or death. The findings demonstrated robust immune responses, with significant increases in anti-RBD IgG levels, particularly in groups that had received 3 -6 doses before the booster dose. The BA.4/5 bivalent booster effectively induced neutralizing antibodies against the vaccine strains, providing robust neutralization, including the XBB.1.16 strain. The study also highlighted that individuals with hybrid immunity, especially those assumed infected with the BA.5 strain or who had been infected twice, showed higher levels of robust neutralizing activity against Omicron XBB.1.16. Overall, these results indicate that the BA.4/5 bivalent booster vaccines can induce potent and good antibody responses in emerging Omicron subvariants, supporting its efficacy as a booster in individuals with diverse vaccination histories.

Safety and Efficacy of a Third Dose of the BNT162b2 Vaccine in Liver-Transplanted and Healthy Adolescents.

Objectives: According to our previous study, the 2-dose-BNT162b2 vaccination is less effective against the Omicron variant. This study aimed to assess the safety and efficacy of a 3-dose-BNT162b2 vaccination in liver-transplanted (LT) and healthy adolescents. Methods: LT and healthy adolescents who met the inclusion criteria received a third dose of the BNT162b2 vaccine (30 µg). Antireceptor-binding domain immunoglobulin and T-cell-specific responses to severe acute respiratory syndrome coronavirus 2 spike peptides were assessed 3 months before the third dose (Visit -1) and 0 (Visit 0), 1 (Visit 1), and 2 months (Visit 2) after the third dose. Antinucleocapsid immunoglobulin and neutralizing antibodies were assessed at Visits 0 and 1. Adverse events (AEs) were monitored. Results: Eleven LT and 14 healthy adolescents aged 14.64 (13.2, 15.7) years (44.2% male) had antireceptor-binding domain immunoglobulin geometric mean titers of 1412.47 (95% confidence interval [CI], 948.18-2041.11) and 1235.79 (95% CI, 901.07-1705.73) U/mL at Visit -1 but increased to 38 587.76 (95% CI, 24 628.03-60 460.18) and 29 222.38 (95% CI, 16 291.72-52 401.03) U/mL (P < 0.05) at Visit 1, respectively. This was consistent with neutralizing antibodies (42.29% and 95.37% vs 44.65% and 91.68%, P < 0.001) and interferon-γ-secreting cells in LT and healthy adolescents at Visit 0 versus Visit 1, respectively. For serious AEs, an LT girl with autoimmune overlap syndrome died 5 months postvaccination from acute liver failure. Conclusions: In both LT and healthy adolescents, humoral and cellular immune responses were high after the 3-dose-BNT162b2 vaccination. However, serious AEs were suspected in LT adolescents with autoimmune diseases.

Epidemiology and clinical characteristics of severe acute respiratory infections among hospitalized children under 5 years of age in a tertiary care center in Bangkok, Thailand, 2019-2020.

Background: Acute respiratory infections (ARIs) are common in children and can range in severity from mild self-limiting illnesses to more severe conditions such as pneumonia and respiratory failure. Data on the epidemiology of viral and bacterial pathogens causing ARIs in children are scarce in this region. This study aimed to investigate the epidemiology and clinical manifestations of pathogens in children aged ≤5 years presenting with severe acute respiratory infection (SARI) in Bangkok, Thailand. The impact of rapid multiplex PCR-based testing on clinical management is also explored. Methods: This cross-sectional study enrolled consecutive children aged ≤5 years presenting with SARI at a tertiary care centre in Bangkok, Thailand, between 2019 and 2020. Nasopharyngeal swabs were collected once at admission, and viral and bacterial pathogens were tested using the QIAstat-Dx respiratory panel. Results: A total of 169 children were enrolled in this study. At least one pathogenic virus was detected in 91.7 % of participants. Based on the final diagnoses made upon discharge, 30.2 % had upper respiratory tract infection, whereas 66.3 % had lower respiratory tract infection. Pneumonia was the most common diagnosis (59.2 %). The most common pathogen identified was rhino/enterovirus (45.2 %), followed by respiratory syncytial virus (31.6 %) and parainfluenza virus (14.2 %). Co-infection was found in 15.4 % and was not associated with increased disease severity. Conclusions: This study provides additional insights into the pathogen profiles, clinical diagnosis, and co-infection combinations of ARIs in hospitalized children. This information is useful for diagnosis and treatment of ARIs, as well as implementation of appropriate infection control measures and guidance for future vaccine policy development.

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.

Dynamics of Cytokine, SARS-CoV-2-Specific IgG, and Neutralizing Antibody Levels in COVID-19 Patients Treated with Convalescent Plasma.

Coronavirus disease 2019 (COVID-19) is a contagious illness worldwide. While guidelines for the treatment of COVID-19 have been established, the understanding of the relationship among neutralizing antibodies, cytokines, and the combined use of antiviral medications, steroid drugs, and convalescent plasma therapy remains limited. Here, we investigated the connection between the immunological response and the efficacy of convalescent plasma therapy in COVID-19 patients with moderate-to-severe pneumonia. The study included a retrospective analysis of 49 patients aged 35 to 57. We conducted clinical assessments to determine antibody levels, biochemical markers, and cytokine levels. Among the patients, 48 (98%) were discharged, while one died. We observed significantly higher levels of anti-nucleocapsid, anti-spike, and neutralizing antibodies on days 3, 7, and 14 after the transfusion compared to before treatment. Serum CRP and D-dimer levels varied significantly across these four time points. Moreover, convalescent plasma therapy demonstrated an immunoregulatory effect on cytokine parameters, with significant differences in IFN-ß, IL-6, IL-10, and IFN-α levels observed at different sampling times. Evaluating the cytokine signature, along with standard clinical and laboratory parameters, may help to identify the onset of a cytokine storm in COVID-19 patients and determine the appropriate indication for anti-cytokine treatment.

SARS-CoV-2 infection- induced seroprevalence among children and associated risk factors during the pre- and omicron-dominant wave, from January 2021 through December 2022, Thailand: A longitudinal study.

BACKGROUND: Severe 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 SARS-CoV-2 seroprevalence among children during the omicron wave are limited. We assessed the SARS-CoV-2 infection-induced seroprevalence among children and estimated the associated risk factors for seropositivity. METHODS: A longitudinal serological survey was conducted from January 2021 through December 2022. The inclusion criteria were healthy children between 5 and 7 years old and their parents or legal guardians provided written informed consent. Samples were tested for anti-nucleocapsid (N) IgG and anti-receptor binding domain (RBD) IgG using a chemiluminescent microparticle immunoassay (CMIA), and total anti-RBD immunoglobulin (Ig) was detected using an electrochemiluminescence immunoassay (ECLIA). The vaccination and SARS-CoV-2 infection history were collected. RESULTS: In all, 457 serum samples were obtained from 241 annually followed-up children in this longitudinal serological survey. Of these, 201 participants provided samples at two serial time points-during the pre-omicron and omicron-dominant wave. Overall, seroprevalence induced by SARS-CoV-2 infection increased from 9.1% (22/241) during the pre-omicron to 48.8% (98/201) during the omicron wave. Amongst seropositive individuals, the infection-induced seropositivity was lower in vaccinated participants with two doses of BNT162b2 than in the unvaccinated participants (26.4% vs. 56%; OR, 0.28; 95%CI: 0.14-0.58). Nevertheless, the ratio of seropositive cases per recalled infection was 1.63 during the omicron dominant wave. The overall seroprevalence induced by infection, vaccination, and hybrid immunity was 77.1% (155/201) between January and December 2022. CONCLUSIONS: We report an increase in infection-induced seroprevalence among children during the omicron wave. These findings highlight that a seroprevalence survey can help determine the true rate of infection, particularly in asymptomatic infection, and optimize public health policies and vaccine strategies in the pediatric population.

Neutralizing antibodies against Omicron BA.5 among children with infection alone, vaccination alone, and hybrid immunity.

OBJECTIVES: To assess the binding antibody response and strength of neutralization against Omicron BA.5 in serum samples from children with different antigen exposures (infection/vaccination) and hybrid immunity. METHODS: This study recruited children aged 5-7 years. All samples were tested for anti-nucleocapsid immunoglobulin (Ig)G, anti-receptor binding domain (RBD) IgG, and total anti-RBD Ig. Neutralizing antibodies (nAbs) against Omicron BA.5 were determined using a focus reduction neutralization test. RESULTS: A total of 196 serum samples from unvaccinated children with infection (n = 57), vaccination alone (n = 71), and hybrid immunity (n = 68). Our results showed that 90% of the samples from children with hybrid immunity, 62.2% from two-dose vaccination, and 48% from Omicron infection alone had detectable nAbs against Omicron BA.5. The highest neutralizing titer was observed in infection plus two-dose vaccination, which reached 6.3-fold increase, whereas nAb titers in two-dose vaccination was comparable to Omicron-infected sera. However, sera from pre-Omicron infection and single-dose vaccination failed to neutralize Omicron BA.5; although, the total anti-RBD Ig were comparable with Omicron-infected sera. CONCLUSION: This result highlights that hybrid immunity provided cross-reactive antibodies to neutralize Omicron BA.5 compared with either vaccination or infection alone. The finding emphasizes the importance of vaccination in unvaccinated children who are infected with pre-Omicron or Omicron variants.

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.

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.

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.

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.