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.

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.

Genomic epidemiology and evolutionary analysis during XBB.1.16-predominant periods of SARS-CoV-2 omicron variant in Bangkok, Thailand: December 2022-August 2023.

The growing occurrence of novel recombinants, such as XBB.1.16, has emerged and become predominant, raising concerns about the impact of genomic recombination on the evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study investigated the molecular epidemiological trends and evolution of the Omicron XBB.1.16 epidemic in Bangkok between December 2022 and August 2023. Partial spike and complete genome sequencing of SARS-CoV-2 samples collected from collaborating hospitals were performed. The analysis of 491 partial spike sequences identified 15 distinct lineages, with XBB.1.16 dominating the lineages beginning in March 2023. Phylogenetic analysis revealed at least four distinct XBB.1.16 lineages, suggesting multiple independent introductions into Bangkok. The estimated emergence of XBB.1.16 occurred approximately in January 2022, with an evolutionary rate of 0.79 × 10-3 substitutions per site per year. Monitoring the genomic epidemiology and evolution of XBB.1.16 is vital for the early detection of new strains or emerging variants, which may guide vaccine design and the inclusion of new vaccine strains.

Prevalence and the impact of hepatitis E infection in pediatric liver transplanted recipients with hepatitis in Thailand.

BACKGROUND: The hepatitis E virus (HEV) infection typically causes acute and self-limiting hepatitis. However, chronic infection can occur in immunocompromised hosts. This study determined the prevalence and impact of HEV infection in liver transplanted (LT) children who had transaminitis. METHODS: The demographic data, anti-HEV IgM/IgG, serum/stool HEV RNA, and management for LT children with acute or persistent transaminitis from 2003 to 2020 were retrospectively reviewed. HEV serology was tested by ELISA, and HEV RNA was detected by semi-nested PCR. RESULTS: Seventy-two children with LT with persistent transaminitis with a median age of 4.41 (1.32, 9.14) years (55.6% female) and one with acute hepatitis were investigated for HEV infection. Anti-HEV IgM, anti-HEV IgG, serum, or stool HEV RNA was investigated in 95.8% (N = 69), 93.1% (N = 67), 43.1% (N = 31), and 37.5% (N = 27) of patients, respectively. The prevalence of HEV infection was 37.5% (N = 27). There was no significant difference in characteristics between the HEV-infected and HEV-non-infected patients. Moreover, 22.2% (N = 16) and 15.3% (N = 11) of patients had past HEV infection and HEV-related acute or chronic infection, respectively. Most of the patients had primary treatment as the presumed graft rejection without improvement. In two patients, detectable HEV RNA in serum turned undetectable in approximately 2 weeks and 2 months, and liver enzyme levels normalized after reducing immunosuppressive therapy. CONCLUSIONS: The prevalence of HEV infection among pediatric LT recipients with hepatitis was high. Chronic HEV infection was evidenced in two patients. Investigations of HEV infection in pediatric LT recipients with persistent transaminitis should guide proper management.

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.

Canine respiratory coronavirus in Thailand undergoes mutation and evidences a potential putative parent for genetic recombination.

Canine respiratory coronavirus (CRCoV) is associated with canine infectious respiratory disease complex. Although its detection has been reported worldwide, the genomic characteristics and evolutionary patterns of this virus remain poorly defined. In this study, 21 CRCoV sequences obtained from dogs in Thailand during two episodes (2013-2015, group A; 2021-2022, group B) were characterized and analyzed. The genomic characteristics of Thai CRCoVs changed from 2013 to 2022 and showed a distinct phylogenetic cluster. Phylogenetic analysis of the spike (S) genes divided the analyzed CRCoV strains into five clades. The full-length genome characterization revealed that all Thai CRCoVs possessed a nonsense mutation within the nonstructural gene located between the S and envelope genes, leading to a truncated putative nonstructural protein. Group B Thai CRCoV strains represented the signature nonsynonymous mutations in the S gene that was not identified in group A Thai CRCoVs, suggesting the ongoing evolutionary process of Thai CRCoVs. Although no evidence of recombination of Thai CRCoV strains was found, our analysis identified one Thai CRCoV strain as a potential parent virus for a CRCoV strain found in the United States. Selective pressure analysis of the hypervariable S region indicated that the CRCoV had undergone purifying selection during evolution. Evolutionary analysis suggested that the CRCoV was emerged in 1992 and was first introduced in Thailand in 2004, sharing a common ancestor with Korean CRCoV strains. These findings regarding the genetic characterization and evolutionary analysis of CRCoVs add to the understanding of CRCoVs. IMPORTANCE Knowledge of genomic characterization of the CRCoV is still limited and its evolution remains poorly investigated. We, therefore, investigated the full-length genome of CRCoV in Thailand for the first time and analyzed the evolutionary dynamic of CRCoV. Genomic characterization of Thai CRCoV strains revealed that they possess unique genome structures and have undergone nonsynonymous mutations, which have not been reported in previously described CRCoV strains. Our work suggests that the Thai CRCoVs were not undergone mutation through genetic recombination for their evolution. However, one Thai CRCoV strain PP158_THA_2015 was found to be a potential parent virus for the CRCoV strains found in the United States. This study provides an understanding of the genomic characterization and highlights the signature mutations and ongoing evolutionary process of CRCoV that could be crucial for monitoring in the future.

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.

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.

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.

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.

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.

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.

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.

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.

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

OBJECTIVES: The 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. METHODS: Participants who completed the Oxford/AstraZeneca (hereafter AZD1222) vaccine dose 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 messenger RNA (mRNA) vaccines (BNT162b2, full, or half-dose mRNA-1273) administered 6 months after primary vaccination were determined. RESULTS: A total of 229 individuals enrolled, and waning of immunity was observed 5-7 months after the AZD1222-primed vaccinations. Total receptor-binding domain (RBD) immunoglobulin (Ig) levels, anti-RBD IgG, and focus reduction neutralization test against Omicron BA.1 and BA.2 variants and T cell response peaked at 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 for all vaccines. CONCLUSION: A heterologous mRNA booster provided a significantly superior boost of binding and NAbs levels against the Omicron variant compared with a homologous booster in individuals with AZD1222-primed vaccinations.