Antibody persistence to diphtheria toxoid, tetanus toxoid, Bordetella pertussis antigens, and Haemophilus influenzae type b following primary and first booster with pentavalent versus hexavalent vaccines.

Thailand has incorporated the whole-cell (wP) pertussis vaccine into the expanded program on immunization since 1977 and has offered the acellular pertussis (aP) vaccine as an optional vaccine for infants since 2001. We followed healthy children from a clinical trial (ClinicalTrials.gov NCT02408926) in which children were randomly assigned to receive either pentavalent (DTwP-HB-Hib) or hexavalent (DTaP-IPV-HB-Hib) vaccines for their primary series (administered at 2, 4, and 6 months) and first booster vaccination (18 months). Both groups received Tdap-IPV as a second booster at the age of 4 y. Blood samples were collected for evaluation of antibody persistence to diphtheria toxoid (DT), tetanus toxoid (TT), and Bordetella pertussis (B. pertussis) between 2 and 6 y of age annually, and for the immunogenicity study of Tdap-IPV at 1 month after the second booster. Antibody persistence to Haemophilus influenzae type b (Hib) was followed until 3 y of age. A total of 105 hexavalent-vaccinated children and 91 pentavalent-vaccinated children completed this study. Both pentavalent and hexavalent groups demonstrated increased antibody levels against DT, TT, and B. pertussis antigens following the second booster with Tdap-IPV. All children achieved a seroprotective concentration for anti-DT and anti-TT IgG at 1 month post booster. The hexavalent group possessed significantly higher anti-pertactin IgG (adjusted p = .023), whereas the pentavalent group possessed significantly higher anti-pertussis toxin IgG (adjusted p < .001) after the second booster. Despite declining levels post-second booster, a greater number of children sustained protective levels of anti-DT and anti-TT IgG compared to those after the first booster.

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.

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.

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.

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.

Durability of immune response against omicron BA.2 and BA.4/5 and T cell responses after boosting with mRNA and adenoviral vector-based vaccines following heterologous CoronaVac/ChAdOx-1nCov-19 vaccination.

Heterologous vaccination with inactivated vaccine followed by adenoviral vector-based vaccine has shown superiority in enhancing immune response compared to homologous primary series. However, data comparing immunity decline after a third booster following heterologous CoronaVac/ChAdOx-1nCov-19 has been limited. Here, we assessed neutralizing activity against omicron variant and T cell response at 3 months monitoring in 96 individuals who received ChAdOx-1nCov-19, BNT162b2, or mRNA-1273 as a third dose following heterologous CoronaVac/ChAdOx-1nCov-19. Comparing the antibody levels at 3 and 1 month(s) after the third booster, the results showed a persistence of anti-RBD IgG in all vaccine regimens, with the IgG level waning slower in the ChAdOx-1nCov-19 boosted group (geometric mean ratio (GMR): 0.64 (95%CI: 0.59-0.70)) compared to the BNT162b2 (0.34 (95%CI:0.31-0.38)) and mRNA-1273 boosted groups (0.32 (95%CI: 0.29-0.36)). Neutralizing activity against omicron BA.2 and BA.4/5 dropped by 1.2 to 1.5-fold but remained detectable, with the highest level observed in the mRNA-1273 group, followed by BNT162b2 and ChAdOx-1nCov-19 groups, respectively. Furthermore, the number of individuals with T cell reactivity decreased in BNT162b2 and mRNA-1273 groups, while it increased in ChAdOx-1nCov-19 group at 3-month post-boost compared to 1 month. Data on the durability of immune response could help comprehensively optimize the booster vaccine strategy.

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.

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.

Immunogenicity of the pentavalent DTwP-HB-Hib vaccine (Shan-5) used in the Thai Expanded Program on Immunization compared to the hexavalent DTaP-HB-Hib-IPV and DTwP-HB-Hib (Quinvaxem) vaccines administered to infants at 2, 4, 6 months of age.

BACKGROUND: The pentavalent DTwP-HB-Hib (Shan-5) vaccine was first introduced into the Thailand Expanded Program on Immunization (EPI) in 2019. The Shan-5 vaccine is administered to infants at 2, 4, and 6 months of age, after initial vaccination with monovalent hepatitis B (HepB) and Bacillus Calmette-Guérin (BCG) vaccines at birth. This study compared the immunogenicity of the HepB, diphtheria, tetanus, and Bordetella pertussis antigens incorporated in the EPI Shan-5 vaccine versus the optional pentavalent (DTwP-HB-Hib) Quinvaxem and hexavalent (DTaP-HB-Hib-IPV) Infanrix-hexa vaccine. METHODS: Three-dose Shan-5-vaccinated children were prospectively enrolled at the Regional Health Promotion Centre 5, Ratchaburi province, Thailand, between May 2020 and May 2021. Blood sampling was performed at months 7 and 18. The levels of HepB surface antibody (anti-HBs), anti-diphtheria toxoid (DT) IgG, anti-tetanus toxoid (TT) IgG, and anti-pertussis toxin (PT) IgG were evaluated using commercially available enzyme-linked immunoassays. RESULTS: Anti-HBs levels of ≥10 mIU/mL were achieved in 100 %, 99.2 %, and 99.2 % of infants in the Shan-5 EPI group, hexavalent group and Quinvaxem group one month after four dose immunization (at 0, 2, 4, 6 months of age), respectively. The geometric mean concentrations of the EPI Shan-5 and hexavalent groups were comparable but were higher than those of the Quinvaxem group. At one month after primary vaccination (month 7), infants in the Shan-5 EPI group had significantly higher levels of anti-DT IgG, anti-TT IgG, and anti-PT IgG than infants in the hexavalent and Quinvaxem groups. CONCLUSIONS: The immunogenicity of the HepB surface antigen in the EPI Shan-5 vaccine was similar to that achieved by the hexavalent vaccine, but was higher than that achieved by the Quinvaxem vaccine. The Shan-5 vaccine is highly immunogenic and generates robust antibody responses after primary immunization.

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.

Neutralizing antibody against Enterovirus-A71 in Thai children: A longitudinal study from birth to age 4 years.

Thailand is one of the countries in the Asia-pacific region that has been most affected by the Enterovirus-A71 (EV-A71) epidemic. An individual who is susceptible to EV-A71 may also be infected asymptomatically, thus, a serological assay is a useful tool to estimate the cumulative incidence of infection in the community and to provide guidance for vaccination scheduling. There have been several candidate EV-A71 vaccines, of which three have been approved and licensed in China. The population target for EV-A71 vaccine is children younger than three years of age. In Thailand, there are limited data available on the seroprevalence of EV-A71 neutralizing (NT) antibodies and the timing of seroconversion in children. This study aims to investigate the seroprevalence and seroconversion rate of EV-A71 NT antibody in a cohort of Thai children. Sera were collected at the King Chulalongkorn Memorial Hospital in Bangkok, Thailand from 100 children between 2015 and 2020. Maternal sera were collected on the day of delivery. Serum samples from children were collected at birth (month 0) and at 2, 7, 18, 24, 36, and 48 months of age to test for EV-A71 NT antibody titers using an enzyme-linked immunosorbent assay (ELISA)-based microneutralization test. The seroprotection rate (NT antibody ≥1:16) in children at months 0, 2, 7, 18, 24, 36, and 48 was 81.0%, 60.0%, 9.0%, 10.0%, 13.0%, 17.0%, and 37.1%, respectively. The seroprotection rate was lowest at month 7 due to waning of the maternal antibody and the immunity of children increased with increasing age. At 48 months of age, less than 40% of children were seroprotected. Children at the age of 6 months should be considered a primary target for vaccination.

Levels of antibodies specific to diphtheria toxoid, tetanus toxoid, and Haemophilus influenzae type b in healthy children born to Tdap-vaccinated mothers.

INTRODUCTION: Vaccination of pregnant women protects both women and their newborns against some infectious diseases. Thailand implemented tetanus toxoid (TT) vaccination of pregnant women in 1977, which was replaced by tetanus-diphtheria toxoid (dT) vaccination in 2005. The tetanus-diphtheria-acellular pertussis (Tdap) vaccine has been recommended for pregnant women at 27-36 weeks of gestation since 2012 in several countries. Data on antibody responses to diphtheria toxoid (DT), TT, and Hemophilus influenzae type b (Hib) induced by combined vaccines in children born to TT-vaccinated and/or Tdap-vaccinated mothers are limited. MATERIAL AND METHODS: We investigated anti-DT, anti-TT, and anti-Hib IgG responses in a cohort of Thai children (ClinicalTrial.gov NCT02408926) born to mothers who received a TT-containing and/or the Tdap vaccine during pregnancy. Children born to Tdap-vaccinated mothers were randomized to receive either a hexavalent (Infanrix-hexa) or pentavalent (Quinvaxem) vaccine, whereas children born to TT-vaccinated mothers received only Quinvaxem vaccine at 2, 4, 6, and 18 months of age. IgG levels were evaluated at birth (cord blood), 2 (pre-primary), 7 (post-primary), 18 (pre-booster), and 19 months of age (post-booster) using a commercially available enzyme-linked immunoassay. RESULTS: Seroprotective concentrations of anti-DT, anti-TT, and anti-Hib IgG were achieved in >90% and >99% of children following primary and booster vaccination, respectively. Among children born to Tdap-vaccinated mothers, the pentavalent vaccine induced higher levels of anti-Hib IgG than the hexavalent vaccine after primary and booster vaccination. Significantly higher anti-Hib IgG levels were observed among children receiving the pentavalent vaccine and who were born to TT-vaccinated mothers than among children receiving the pentavalent vaccine and born to Tdap-vaccinated mothers after primary and booster vaccination. CONCLUSIONS: Vaccination with a TT-containing and/or the Tdap vaccine during pregnancy did not compromise the seroprotection rate achieved following primary and booster immunization in individuals receiving either the pentavalent or hexavalent vaccine.

Antibodies to measles, mumps, and rubella virus in Thai children after two-dose vaccination at 9 months and 2.5 years: A longitudinal study.

INTRODUCTION: Thailand changed the schedule of childhood measles-mumps-rubella (MMR) vaccination in 2014, moving the second dose from the age of 6 years to 2.5 years. There are currently no data on antibody responses to the MMR vaccine since this recommendation. MATERIAL AND METHODS: We investigated antibody responses in a cohort of children who received two doses of MMR vaccine at the ages of 9 months and 2.5 years that was originally established to evaluate antibody levels to Bordetella pertussis antigens (ClinicalTrials.gov no. NCT02408926). Infants were born to mothers who previously received tetanus-diphtheria-acellular pertussis vaccine at 27-36 weeks of gestation. Anti-measles, -mumps, and -rubella virus IgG levels were measured at birth (cord blood) and the ages of 2 and 7 months (before the first MMR vaccination); 18 and 24 months (9 and 15 months, respectively, after the first dose); and 36 months (6 months after the second dose) using commercially available enzyme-linked immunosorbent assay kits. RESULTS: At 7 months of age, 96.2%, 99.6%, and 98.8% of infants had no protection against measles, mumps, and rubella, respectively. Levels of antibody against all three antigens increased significantly after the first but not the second dose. At 6 months after two-dose vaccination, 97.4%, 84.8%, and 78.7% of children remained seroprotected against measles, mumps, and rubella, respectively. CONCLUSIONS: Maternally derived antibodies to measles, mumps, and rubella virus disappeared by the age of 7 months in Thai children. Two-dose MMR vaccination at 9 months and 2.5 years of age induced robust immune responses against these viruses.