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.

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.

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.

Genome sequences of chikungunya virus isolates from an outbreak in southwest Bangkok in 2018.

An outbreak of chikungunya virus (CHIKV) infection occurred in southwest Bangkok during the 2018 rainy season. The envelope glycoprotein E1 gene sequence of the infecting strain belonged to an East/Central/South African lineage with alanine at residue 226. Mutations in the predicted E1 (K211E) and E2 (V264A) proteins of CHIKV were identified in CHIKV-infected patients and in an Aedes aegypti mosquito. Analysis of the complete genome sequences showed marked differences from the strains causing previous outbreaks in Thailand in 2008-2009 and 2013 but showed similarities to strains from more recent CHIKV outbreaks in South and Southeast Asia.

Hepatitis E virus infection in Thai blood donors.

BACKGROUND: Hepatitis E virus (HEV) infection in several industrialized and developing countries is associated with the consumption of pork and other meat products, an exposure risk among the majority of blood donors. We aimed to evaluate the prevalence of HEV in plasma from healthy blood donors in Thailand. STUDY DESIGN AND METHODS: We screened blood samples collected between October and December 2015, from 30,115 individual blood donors in 5020 pools of six, for HEV RNA using in-house real-time reverse-transcription polymerase chain reaction (RT-PCR). Thrice-reactive samples were subjected to a commercial real-time RT-PCR (cobas HEV test) and evaluated for anti-HEV immunoglobulin M and immunoglobulin G antibodies. Genotyping using nested RT-PCR, nucleotide sequencing, and phylogenetic analysis was performed. RESULTS: Twenty-six donors were positive for HEV RNA by the in-house assay, nine of whom were also positive by cobas test. None of the latter were reactive for anti-HEV immunoglobulin M or immunoglobulin G antibodies. Six samples were successfully genotyped and found to be HEV genotype 3. Thus, the frequency of HEV infection among healthy Thai blood donors is 1 in 1158. CONCLUSION: The presence of HEV RNA in the Thai blood supply was comparable to the rates reported in western European countries, but higher than in North America and Australia.

Frequency of HLA-DQB1*0201/02 and DQB1*0302 alleles and tissue transglutaminase antibody seropositivity in children with type 1 diabetes mellitus.

BACKGROUND: Patients with type 1 diabetes mellitus (T1DM) have an increased risk of celiac disease (CD). Both diseases have a common genetic susceptibility locus in the human leukocyte antigen (HLA) class II alleles. Testing for tissue transglutaminase antibodies (anti-tTG) is highly accurate for a CD diagnosis. OBJECTIVE: To determine the frequency of HLA-DQB1*0201/02 and DQB1*0302 alleles and anti-tTG seropositivity in children with T1DM. METHOD: Forty-six children with T1DM (male:female=24:22; mean age 12±3.7 years) without significant digestive symptoms were enrolled. The mean duration of diabetes was 5±3.5 years. Serum anti-tTG IgA and IgG as well as HLA-DQ2 (DQB1*0201/02) and -DQ8 (DQB1*0302) alleles were analyzed. The allele frequencies were compared with those in controls, which included 124 normal Thai individuals, as reported in our previous study. RESULTS: All subjects were negative for anti-tTG IgG. Only one patient (2.2%) was positive for anti-tTG IgA (38.5 U/mL; cut-off 15 U/mL). Although this patient was also heterozygous for HLA-DQ2 and was asymptomatic for CD, he declined endoscopic confirmation. Twenty-nine of 46 patients carried HLA-DQ2 and/or -DQ8 heterodimers. HLA-DQB1*0201/02 and HLA-DQB1*0302 allele frequencies were significantly higher (27% and 14%) in T1DM patients compared with normal controls (13.3% and 7.3%; P<0.001 and P=0.002, respectively). CONCLUSIONS: A significantly greater frequency of DQB1*0201/02 and DQB1*0302 alleles were present in children with T1DM compared with the control group. This indicates a potentially important role of these alleles in the development of T1DM. The prevalence of CD screening by serologic testing is negligible in Thai children with T1DM.

Lineage-specific detection of influenza B virus using real-time polymerase chain reaction with melting curve analysis.

Influenza B viruses comprise two lineages, Victoria (B/Vic) and Yamagata (B/Yam), which co-circulate globally. The surveillance data on influenza B virus lineages in many countries often underestimate the true prevalence due to the lack of a rapid, accurate, and cost-effective method for virus detection. We have developed a real-time PCR with melting curve analysis for lineage-specific differential detection of influenza B virus. By amplifying a region of the hemagglutinin gene using real-time PCR with SYBR Green I dye, B/Vic and B/Yam could be differentiated based on their melting temperature peaks. This method was efficient (B/Vic = 93.2 %; B/Yam 97.7 %), sensitive (B/Vic, 94.6 %; B/Yam, 96.3 %), and specific (B/Vic, 97.7 %; B/Yam, 97.1 %). The lower detection limit was 10(2) copies per microliter. The assay was evaluated using 756 respiratory specimens that were positive for influenza B virus, obtained between 2010 and 2015. The incidence of influenza B virus was approximately 18.9 % of all influenza cases, and the percentage was highest among children aged 6-17 years (7.57 %). The overall percentage of mismatched influenza B vaccine was 21.1 %. Our findings suggest that real-time PCR with melting curve analysis can provide a rapid, simple, and sensitive lineage-specific influenza B virus screening method to facilitate influenza surveillance.

Diagnostic accuracy of urine heparin binding protein for pediatric acute pyelonephritis.

UNLABELLED: Timely antibiotic initiation for acute pyelonephritis (APN) can prevent renal complications. We investigated whether urine heparin binding protein (UHBP), a cytokine released from activated neutrophils, was a useful diagnostic tool for APN. Febrile children with presumed APN were prospectively enrolled between January and September 2013, and divided into two groups based on urine cultures. UHBP levels were measured at enrollment in all children and 1 month after antibiotic treatment in children with APN. UHBP levels in children with APN at baseline and 1 month versus controls were 47.0 ± 8.4 and 16.6 ± 3.8 vs. 15.0 ± 2.9 ng/mL, respectively (p < 0.001). Test performance characteristics were calculated against a gold standard of positive urine cultures and compared with leukocyte esterase (LE) and nitrite measured by dipsticks and pyuria by microscopy. The sensitivity and specificity for UHBP levels ≥34 ng/mL were 100 and 100 %. Spearman's rank coefficient was used to assess the associations between routine laboratory tests and UHBP levels. Significant positive correlations were found with pyuria grade (Spearman's rho = 0.62; p < 0.001), neutrophil count (rho = 0.38; p = 0.03), and platelet count (rho = 0.39; p = 0.03). CONCLUSIONS: UHBP is a valid adjunctive diagnostic tool for aiding clinicians in making rapid treatment decisions for APN.

Seroprevalence of antibodies against varicella zoster virus across all age groups during the post-COVID-19 pandemic period in Chonburi Province, Thailand.

As of 2024, Thailand has not incorporated the varicella-zoster virus (VZV) vaccine into the Expanded Program on Immunization (EPI). This study aimed to evaluate VZV seroprevalence across all age groups in Chonburi Province, Thailand, during the post-COVID-19 era, and to support the development of a vaccination plan against VZV. A total of 950 participants were enrolled from October 2022 to January 2023. VZV antibody levels were measured using ELISA kits (EUROIMMUN, Lübeck, Germany), with seropositivity set at ≥110 IU/L. The overall VZV seropositivity rate was 64.8%, similar to rates in 1994 and 2014. However, seropositivity rates for the 5-9, 10-14, and 15-19 age groups were significantly higher in the 1994 study, and for the 10-14 and 15-19 age groups in the 2014 study, indicating a declining trend among young Thai individuals. The seropositivity rate increased with age, with a seroprevalence exceeding 80% in individuals aged 30 years and older. Our study found a significant association between the history of varicella and seropositivity. Thus, a positive history may indicate immunity. In conclusion, a significant portion of Thai adolescents are still vulnerable to varicella, highlighting the crucial role of vaccination in averting serious illness.

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.

Persistence of Antibodies against Measles, Mumps, and Rubella after the Two-Dose MMR Vaccination: A 7-Year Follow-Up Study.

In 2014, the Expanded Program on Immunization of Thailand changed the timing of the second dose of the measles-mumps-rubella (MMR) vaccine from 4-6 years to 2.5 years, while maintaining the first dose at 9 months of age. This study aimed to examine the dynamics and durability of immune responses induced by the two-dose MMR vaccine in a group of 169 Thai children from 4 to 7 years of age (4.5 years after the second MMR dose). We followed a cohort of healthy children from a clinical trial (ClinicalTrials.gov NCT02408926) where they were administered either the Priorix vaccine (GlaxoSmithKline Biologicals, Rixensart, Belgium) or M-M-RII (Merck & Co., Kenilworth, NJ, USA) at 9 months and 2.5 years of age. Blood samples were collected annually from ages 4 to 7 years. Anti-measles, -mumps, and -rubella IgG levels were evaluated using the enzyme-linked immunosorbent assay (EUROIMMUN, Lubeck, Germany). A total of 169 children completed this study. Over the 4.5 years following the two-dose MMR vaccination, we observed a decline in the seroprotection rates against measles and mumps, but not rubella. Longitudinal monitoring of antibody persistence, among other strategies, will help predict population-level immunity and inform public health interventions to address potential future outbreaks.

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.

Hepatitis E virus genotype 3f sequences from pigs in Thailand, 2011-2012.

Phylogenetic analysis of partial ORF1 and ORF2 genes of Hepatitis E virus (HEV) strains from pigs in Thailand during 2011-2012 was performed. The result indicated that the current Thai strains belonged to the genotype 3 subgroup 3f, which were similar to the previous HEVs circulating in humans in Thailand.

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

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

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.

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.

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.