The immunogenicity and reactogenicity of four COVID-19 booster vaccinations against SARS-CoV-2 variants following CoronaVac or ChAdOx1 nCoV-19 primary series.

BACKGROUND: The appropriate COVID-19 booster vaccine following inactivated or adenoviral vector COVID-19 vaccination is unclear. OBJECTIVE: To investigate the immunogenicity of four COVID-19 booster vaccines. METHODS: We prospectively enrolled healthy adults who received a two-dose CoronaVac or ChAdOx1 8-12 weeks earlier and allocated them to receive one of the following booster vaccine: inactivated (BBIBP-CorV), ChAdOx1 or mRNA (BNT162b2 at full [30 µg] and half [15 µg] dose) vaccines. We determined the reactogenicity and the humoral (anti-receptor binding domain IgG (anti-RBD-IgG), neutralizing antibodies (nAb) against Delta, Beta and Omicron variants) and cellular immunity measuring by interferon gamma (IFN-γ) responses post-booster. AR patients. RESULTS: Among the 352 participants (179 CoronaVac and 173 ChAdOx1 participants), 285 (81%) were female, and median age was 39 (IQR: 31-47) years. Two weeks post-booster, both 30 µg- and 15 µg- BNT162b2 induced the highest anti-RBD IgG concentration (BAU/mL); Coronavac-prime: 30 µg-BNT162b2, 5152.2 (95%CI 4491.7-5909.8); 15 µg-BNT162b2, 3981.1 (3397.2-4665.4); ChAdOx1, 1358.0 (1141.8-1615.1); BBIBP-CorV, 154.6 (92.11-259.47); ChAdOx1-prime: 30 µg-BNT162b2, 2363.8 (2005.6-2786.1; 15 µg-BNT162b2, 1961.9 (1624.6-2369.1); ChAdOx1, 246.4 (199.6-304.2); BBIBP-CorV, 128.1 (93.5-175.4). Similarly, both 30 µg- and 15 µg- BNT162b2 boosting induced the highest nAb titers against Beta, Delta and Omicron BA.1 variants and highest T-cell response at 2 weeks after boosting. While all BNT162b2 or heterologous ChAdOx1-boosted participants had nAb against Omicron, these were < 50% for BBIBP-CorV and 75% for homologous ChAdOx1-boosted participants. There was significant decrease in nAb ( > 4-fold) at 16-20 weeks post booster for all groups. CONCLUSIONS: Heterologous boosting with BNT162b2 following CoronaVac or ChAdOx1 primary series is most immunogenic. Additional studies are needed to verify the clinical efficacy and persistence of immunity following half-dose BNT162b2.

Seroprevalence of Bordetella pertussis antibodies and anti-pertussis antibody response after a single dose of reduced-antigen combined diphtheria, tetanus, and acellular pertussis vaccine (Tdap) in pregnant Thai women.

BACKGROUND: Maternal immunization with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) has recently been implemented to prevent infant pertussis. Tdap is still not routinely recommended in Thailand, and there are limited data to support or challenge this strategy. OBJECTIVES: The primary aim was to determine the seroprevalence of anti-pertussis toxin antibodies (anti-PT IgG) among pregnant Thai women. The secondary aims were to evaluate antibodies response after Tdap vaccination between seronegative and seropositive mothers and to compare the different antibody titers at delivery among seropositive mothers who received Tdap to those who received tetanus-diphtheria vaccine (Td). METHODS: This randomized clinical trial was conducted during April 2018 to April 2019 at Siriraj Hospital, Bangkok, Thailand. A total of 129 pregnant women were included. Paired blood samples for anti-PT IgG levels were obtained during the first antenatal visit and at delivery. A baseline cut-off value of <5 IU/ml indicated seronegativity. There were 29 exclusions from the original 129 enrollment. All seronegative participants (n = 69) received Tdap, while the seropositive group were randomized 1:1 to receive either Tdap (n = 18) or Td (n = 13) during 27-36 weeks' gestation. The antibody levels from both sera were compared between groups. RESULTS: The seroprevalence of maternal anti-PT IgG was 33.3% (43/129). There was no significant difference in the increment of antibody levels after Tdap vaccination between the seronegative and seropositive groups (30.2 vs. 42 IU/ml; p = 0.183). Among seropositive groups, all Tdap recipients had increased antibody titers at delivery, while all Td recipients showed waning of immunity throughout gestation. (42 IU/ml vs. -7.4 IU/ml; p < 0.001). CONCLUSION: Most pregnant Thai women have seronegative against pertussis. Most seropositive mothers had initial low antibody titers and their immunity significantly decreased before delivery. Our findings highlight the need for universal pertussis immunization in pregnancy regardless of individual baseline immunity.

Clinical outcome and laboratory markers for predicting disease activity in patients with disseminated opportunistic infections associated with anti-interferon-γ autoantibodies.

BACKGROUND: Clinical courses and treatment outcomes are largely unknown in patients with adult-onset immunodeficiency associated with anti-interferon-gamma autoantibodies due to the fact that it was recently recognized and anti-IFN-γ auto-Abs detection is not widely available. METHODS AND FINDINGS: Non-HIV-infected adult patients with detectable anti-IFN-γ auto-Abs diagnosed and followed at Siriraj Hospital, Bangkok, Thailand during January 2013 to November 2016 were prospectively studied. At each follow-up visit, patients were classified as stable or active disease according to symptoms and signs, and all proven OIs were recorded. Laboratory parameters, including erythrocyte sedimentation rate, C-reactive protein, and anti-IFN-γ auto-Abs level, were compared between active and stable disease episodes. We identified 80 patients with this clinical syndrome and followed them up during study period. Seventy-nine patients developed overall 194 proven opportunistic infections. Mycobacterium abscessus (34.5%) and Salmonella spp. (23.2%) were the two most common pathogens identified among these patients. Sixty-three patients were followed for a median of 2.7 years (range 0.6-4.8 years). Eleven (17.5%) patients achieved the drug-free remission period for at least 9 months. Four patients died. Anti-IFN-γ auto-Abs concentration was significantly lower at baseline and decreased over time in the drug-free remission group compared to another group (p = 0.001). C-reactive protein, erythrocyte sedimentation rate and white cell count were found to be useful biomarkers for determining disease activity during follow-up. CONCLUSIONS: Reinfection or relapse of OIs is common despite long-term antimicrobial treatment in patients with anti-IFN-γ auto-Abs. Treatment to modify anti-IFN-γ auto-Abs production may improve long-term outcomes in this patient population.

Effects of 1α,25 Dihydroxyvitamin D3 on Pro-inflammatory Cytokines of Palmitic Acid Treated Thp-1 Cells.

The level of saturated fatty acids, such as palmitic acid (PA), correlates with chronic inflammation in obese and metabolic syndrome patients. However, low level of vitamin D3 is observed in those conditions. The aim of this study is to investigate effects of 1α,25(OH)2 D3 on PA-treated THP-1 cells. Using quantitative real-time polymerase chain reaction, we measure mRNA expression of pro-inflammatory cytokines: TNF-α, Interleukin (IL)-1ß, IL-6, and chemokine IL-8 under PA and 1α,25(OH)2 D3 influence. PA, at all concentrations (25-100 µM), enhanced LPS stimulatory effect on those mRNA expression compared to LPS-treated and -untreated cells. Combination with 1α,25(OH)2 D3 increased cytokine expression at high (10-6 M) and high-normal (10-8 M) concentrations compared to PA + LPS and LPS alone, both for 2 and 24 h. However, low-normal (10-10 M) and low (10-12 M) levels of 1α,25(OH)2 D3 could not enhance PA effect, but mRNA expression of pro-inflammatory cytokine was higher than LPS-treated cells. Upstream pathway of 1α,25(OH)2 D3 , which is cholecalciferol, also gave the similar result. Further, inhibition of calcium pathway does not play a role in this mechanism. Thus, these findings support pro-inflammatory effect of PA and vitamin D3 on innate immune response, especially on fat-induced inflammation. PRACTICAL APPLICATION: The effect of vitamin D3 on chronic inflammation in obesity is uncertain. This study shows an in vitro possibility that vitamin D3 could exaggerate inflammation when combined with high SFAs. The idea of using vitamin D3 supplement to modulate inflammation in fat-related inflammation needs further refined experiments before its clinical application.

Factors associated with acquired Anti IFN- γ autoantibody in patients with nontuberculous mycobacterial infection.

BACKGROUND: The clinical syndrome of disseminated nontuberculous mycobacterial (NTM) infection in patients who were previously healthy is now well recognized to be associated with an acquired autoantibody to Interferon gamma (Anti IFN- γ autoantibody). However, the risk factors of this syndrome remain unknown. METHOD: We performed an unmatched case control study among patients with NTM diseases who were diagnosed and treated at Siriraj Hospital, Bangkok, Thailand. Anti-IFN autoantibody was detected by enzyme-linked immunosorbent assay (ELISA) method. Cases were patients with NTM diseases and detectable anti IFN- γ autoantibody. Controls were randomly selected from those with undetectable anti IFN- γ autoantibody. Data from both groups including demographic data, clinical presentation, laboratory results, other risk factors and HLA genotypes were collected. Univariate and multivariate analyses were performed to identify independent risk factors for this syndrome. RESULTS: 70 cases (mean age 50 ± 11 years) and 70 controls (mean age 58 ± 18 years) were enrolled into the study. Mycobacterial abscessus was the most common NTM pathogen found in both groups (72.9% in cases and 41.4% in controls respectively). However, disseminated NTM disease was significantly more common in cases (92.9%) than in the controls (14.3%, p<0.001). Binary logistic regression analysis showed that previous OIs (adjusted OR14.87, 95% CI 2.36-93.86), birthplace outside Central region (adjusted OR 19.19, 95% CI 3.86-95.35), lack of comorbidities lead to immunosuppression, such as HIV infection or diabetes mellitus (adjusted OR 23.68, 95% CI 4.01-139.94), and presence of HLA DRB1*15/16 (adjusted OR 153.28, 95% CI 16.87-139.88) were independent factors associated with this syndrome. CONCLUSION: Patients with NTM disease associated with anti IFN- γ autoantibody are almost always previously healthy and HIV negative. Most of these patients presented with disseminated NTM disease with generalized lymphadenitis and often with reactive skin lesions. Factors associated with detectable anti IFN- γ autoantibody are HLA-DRB1 and DQB1 alleles, and history of previous OIs in patients without comorbidity that leads to immunosuppression. Further studies are needed to better understand these associations and to improve the treatment outcome.

HLA-DRB1 and HLA-DQB1 Are Associated with Adult-Onset Immunodeficiency with Acquired Anti-Interferon-Gamma Autoantibodies.

Recently a newly identified clinical syndrome of disseminated non-tuberculous mycobacterial diseases (with or without other opportunistic infections in adult patients who were previously healthy, has been recognized in association with an acquired autoantibody to interferon-gamma. This syndrome is emerging as an important cause of morbidity and mortality, especially among people of Asian descent. Trigger for the production of this autoantibody remains unknown, but genetic factors are strongly suspected to be involved. We compared HLA genotyping between 32 patients with this clinical syndrome, and 38 controls. We found that this clinical syndrome was associated with very limited allele polymorphism, with HLA-DRB1 and DQB1 alleles, especially HLA-DRB1*15:01, DRB1*16:02, DQB1*05:01 and DQB1*05:02. Odds ratio of DRB1*15:01, DRB1*16:02, DQB1*05:01 and DQB1*05:02 were 7.03 (95% CI, 2.18-22.69, P<0.0001, 9.06 (95% CI, 2.79-29.46, P<0.0001), 6.68 (95% CI, 2.29-19.52, P = 0.0004), and 6.64 (95% CI, 2.30-19.20, P = 0.0004), respectively. Further investigation is warranted to provide better understanding on pathogenesis of this association.

The immunogenicity and safety of pneumococcal conjugate vaccine in human immunodeficiency virus-infected Thai children.

BACKGROUND: HIV-infected children have high risk of invasive pneumococcal disease (IPD) despite receiving highly active antiretroviral therapy (HAART). This study aimed to determine the immunogenicity and safety of a 7-valent pneumococcal conjugate vaccine (PCV-7) in Thai HIV-infected children compared to HIV-exposed uninfected children. METHODS: A prospective study was conducted among children 2 months to 9 years. The number of PCV-7 doses depended upon age and HIV status; 2-6 months of age: 3 doses; 7-23 months of age: 2 doses; HIV-infected child ≥24 months: 2 doses and HIV-exposed child ≥24 months: 1 dose. Serotype-specific pneumococcal IgG antibody concentrations were measured at baseline and 28 days after complete vaccination. The primary end point was the proportion of children who achieved serotype-specific IgG antibody concentration at a cut off level ≥0.35 µg/mL. Secondary end points were a 4-fold increase in serotype-specific IgG antibody, rates of adverse events and predictors for seroconversion among HIV-infected children. RESULTS: Fifty-nine HIV-infected and 30 HIV-exposed children were enrolled. The median (IQR) age was 97 (67-111) and 61 months (51-73), respectively (p<0.001). Among HIV-infected children, current and nadir CD4 counts were 1,079 cell/mm(3) and 461 cell/mm(3), respectively. The proportion of children who achieved pneumococcal IgG ≥0.35 µg/mL was in the range of 85-98% in HIV-infected and 83-100% in HIV-exposed children depending on serotype. The lowest response was to serotype 6B in both groups. The 4-fold increase in serotype-specific IgG concentrations was similar between HIV-infected and HIV-exposed groups, except for serotype 9V (p=0.027). HIV-infected children who had a history of AIDS had a lower antibody response to serotype 23F (p=0.025). Seven (12%) HIV-infected children had a grade 3 local reaction. CONCLUSION: PCV-7 is highly immunogenic and safe among HIV-infected children treated with HAART. The use of the pneumococcal conjugate vaccine among HIV-infected children is encouraged in order to prevent IPD.