A phase III, multicenter, randomized, double-blind, active comparator-controlled study to evaluate the safety, tolerability, and immunogenicity of catch-up vaccination regimens of V114, a 15-valent pneumococcal conjugate vaccine, in healthy infants, children, and adolescents (PNEU-PLAN)

Background: Despite widespread use of pneumococcal conjugate vaccines (PCVs) in children, morbidity and mortality caused by pneumococcal disease (PD) remain high. In addition, many children do not complete their PCV course on schedule. V114 is a 15-valent PCV that contains two epidemiologically important serotypes, 22F and 33F, in addition to the 13 serotypes present in PCV13, the licensed 13-valent PCV. Methods: This phase III descriptive study evaluated safety and immunogenicity of catch-up vaccination with V114 or PCV13 in healthy children 7 months–17 years of age who were either pneumococcal vaccine-naïve or previously immunized with lower valency PCVs (NCT03885934). Overall, 606 healthy children were randomized to receive V114 (n = 303) or PCV13 (n = 303) via age-appropriate catch-up vaccination schedules in three age cohorts (7–11 months, 12–23 months, or 2–17 years). Results: Similar proportions of children 7–11 months and 2–17 years of age reported adverse events (AEs) in the V114 and PCV13 groups. A numerically greater proportion of children 12–23 months of age reported AEs in the V114 group (79.0%) than the PCV13 group (59.4%). The proportions of children who reported serious AEs varied between different age cohorts but were generally comparable between vaccination groups. No vaccine-related serious AEs were reported, and no deaths occurred. At 30 days after the last PCV dose, serotype-specific immunoglobulin G geometric mean concentrations were comparable between vaccination groups for the 13 shared serotypes and higher in the V114 group for 22F and 33F. Conclusions: Catch-up vaccination with V114 in healthy individuals 7 months–17 years of age was generally well tolerated and immunogenic for all 15 serotypes, including those not contained in PCV13, regardless of prior pneumococcal vaccination. These results support V114 catch-up vaccination in children with incomplete or no PCV immunization per the recommended schedule.publishedVersionPeer reviewe

Streptococcus pneumoniae Causing Invasive Diseases in Children and Adults in Central Thailand, 2012–2016

Longitudinal data regarding the serotype distribution and antimicrobial susceptibility of S. pneumoniae-causing invasive pneumococcal disease (IPD) in developing countries are limited. Our aim was to monitor the antimicrobial susceptibility, serotype distribution, and serotype coverage rates of the pneumococcal conjugate vaccines (PCVs) and emerging non-vaccine serotypes (NVT) between 2012 and 2016 in central Thailand. Pneumococcal isolates from sterile specimens of patients, collected within a long-standing collaborative hospital network in central Thailand between 2012 and 2016, were studied. The pneumococcal serotypes included in the 15-valent PCV were identified by the quellung reaction, while the non-PCV15 serotypes were identified by multiplex PCR. Antimicrobial susceptibilities were determined by the microbroth dilution or disk diffusion method. Of the 276 pneumococcal isolates, 129 (46.7%) were from children aged ≤5 years. Only 9.0% of patients with available data received the PCV prior to the onset of the IPD. The most common vaccine serotypes were 6B (17.4%), 19A (13.0%), and 14 (11.2%), respectively. Non-PCV15 serotypes were detected in 27.9%; the most common serotypes were 15B/C (5.1%), 15A/F (4.0%), and 23A (3.6%), respectively. The serotype coverage rates of PCV10 in children aged ≤5 years was 55.8%, and 53.3% across all ages. PCV13 provided similar coverage rates to that of PCV15, 71.3% in children aged ≤5 years, and 72.1% across all ages. High susceptibilities to cefotaxime (94.6%), ofloxacin (98.2%), linezolid (99.6%), and vancomycin (100.0%) were observed, while the susceptibility to erythromycin (50.0%), TMP-SMZ (41.3%), and tetracycline (27.2%) were low. The susceptibilities to penicillin, meropenem, and clindamycin were 85.9%, 85.9%, and 84.8%, respectively. Serotype 19A was associated with a lower susceptibility than the non-19A isolates for penicillin (75.0% vs. 87.5%, p = 0.045), meropenem (52.8% vs. 90.8%, p < 0.001), erythromycin (33.3% vs. 53.8%, p = 0.022), and TMP-SMZ (16.7% vs. 45.0%, p = 0.001). Although the majority of the pneumococcal serotypes causing IPD in central Thailand were covered by the currently available PCVs, 25% of IPD were caused by NVT. Several emerging NVT identified were 15B/C, 15A/F, and 23A. The high rates of resistance to penicillin, meropenem, erythromycin, TMP-SMZ, and tetracycline observed is a major concern. Serotype 19A was associated with lower antimicrobial susceptibilities in comparison to the non-19A serotypes

Immunogenicity and Reactogenicity of mRNA BNT162b2 COVID-19 Vaccine among Thai Adolescents with Chronic Diseases

Adolescents with underlying diseases are at risk of severe COVID-19. The immune response of BNT162b2 may be poor among immunocompromised adolescents. We aim to describe immunogenicity of mRNA BNT162b2 among adolescents who are immunocompromised or have chronic diseases. We recruited adolescents 12–18 years of age; group A impaired-immunity (post-transplantation, cancer, on immunosuppressive drugs) and group B chronic diseases. A two-dose regimen of BNT162b2 was given. Immunogenicity was determined by surrogate virus neutralization test (sVNT) and IgG against receptor-binding domain (RBD). From August to October 2021, 312 adolescents, with a median age (IQR) of 15 years (13.7–16.5), were enrolled (group A 100, group B 212). The geometric means (GMs) of sVNT (% inhibition) against Delta strain and anti-RBD IgG (BAU/mL) after the 2nd dose among group A were: post-transplantation recipients 52.9 (95% CI 37.7–74.2) and 233.6 (95% CI 79–690.6); adolescents with cancer 62.3 (95% CI 29.2–133.1) and 214.9(95% CI 34.2–1348.6); and adolescents with other immunosuppressive conditions 66.7 (95% CI 52.4–84.8) and 849.8 (95% CI 393.4–1835.8). In group B were: adolescents living with HIV 98 (95% CI 97.3–98.8) and 3240.3 (95% CI 2699–3890.2), and adolescents with other chronic disease 98.6 (95% CI 98.3–98.9) and 3818.5 (95% CI 3490.4–4177.4). At day 90, immunity declined; among impaired-immunity participants were 43.9 (95% CI 30.8–62.4) and 178.7 (95% CI 91.2–350.1) and adolescents with chronic diseases were 90.6 (95% CI 88.4–92.8) and 1037.1 (95% CI 933.3–1152.5). In conclusion, adolescents with impaired immunity had a poor response to 2-doses of BNT162b2, additional dose should be considered. Adolescents with chronic diseases had excellent response but immunity waned after 3 m, booster dose may be required

Metabolic Disorders in HIV-Infected Adolescents Receiving Protease Inhibitors

Protease inhibitor (PI) may cause abnormal glucose metabolism, abnormal lipid metabolism, and metabolic syndrome in HIV-infected adults but less well studied in Asian adolescents. This cross-sectional study evaluated anthropometric factors, oral glucose tolerance test, and lipid profiles of perinatally HIV-infected Thai adolescents who had received PI-based antiretroviral therapy for at least 6 months. Eighty adolescents were enrolled [median (IQR) age 16.7 (14.6–18.0) years, 42 males]. Metabolic syndrome, prediabetes, and type 2 diabetes mellitus (T2DM) were found in 8 (10%), 17 (22.1%), and 3 (3.8%) adolescents, respectively. Dyslipidemia was found in 56 (70%) adolescents, with hypertriglyceridemia being the most common type. In multivariate analysis, presence of lipohypertrophy (OR: 25.7, 95% CI: 3.2–202.8; p=0.002) and longer duration of PI use (OR: 1.04, 95% CI: 1.00–1.08; p=0.023) were associated with metabolic syndrome. Obesity (OR: 7.71, 95% CI: 1.36–43.7; p=0.021), presence of lipohypertrophy (OR: 62.9, 95% CI: 4.97–795.6; p=0.001), and exposure to stavudine for ≥6 months (OR: 8.18, 95% CI: 1.37–48.7; p=0.021) were associated with prediabetes/T2DM, while exposure to tenofovir for ≥6 months reduced the risk (OR: 0.17, 95% CI: 0.04–0.78; p=0.022). Metabolic disorders were commonly found in adolescents receiving PI. Careful monitoring and early intervention to modify cardiovascular risk should be systematically implemented in this population particularly those with exposure to stavudine

A pilot program of HIV pre-exposure prophylaxis in Thai youth.

IntroductionThere are gaps in knowledge and experience of antiretroviral pre-exposure prophylaxis (PrEP) delivery in adolescents.MethodsThis pilot study enrolled Thai adolescents 14-20 year-old without HIV who reported risk behaviour. All participants were offered daily tenofovir/emtricitabine (TDF-FTC) and followed for 24 weeks. HIV testing, renal function, bone density scan, and sexually transmitted infection (STI) testing including syphilis serology and urine molecular testing for gonorrhoea and C. trachomatis were performed at baseline and weeks 12 and 24. Adherence was evaluated through intracellular tenofovir diphosphate (TFV-DP) levels in dried blood spots.ResultsOf the 61 enrolled adolescents, median age 18.1 (IQR: 14.8-20.9) years, 46 (75.4%) were males and 36 (59%) were MSM. Retention to week 24 was 80.3%. One third (36%) had TFV-DP levels consistent with taking ≥6 pills/week at week 12 and 29% at week 24. The factors associated with taking ≥6 pills/week were being MSM (adjusted odds ratio [aOR]: 53.2, 95% CI: 1.6-1811; p = 0.027), presence of STI at baseline (aOR: 9.4, 95% CI: 1.5-58.5; p = 0.016), and self-report of decreased condom use while taking PrEP (aOR: 8.7, 95% CI: 1.4-56.6; p = 0.023). 31% had an STI at baseline and this declined to 18% at week 24. No renal or bone toxicity was observed and there were no HIV seroconversions.ConclusionsDaily oral PrEP with FTC-TDF in high-risk Thai adolescents is feasible, accepted, well-tolerated, and had no increased risk compensation; however, low adherence was a major challenge. Adolescent-specific PrEP strategies including long-acting modalities are needed for successful HIV prevention

Immunogenicity of a Two-Dose Human Papillomavirus Vaccine Schedule in HIV-Infected Adolescents with Immune Reconstitution

HIV-infected patients are at increased risk of human papillomavirus (HPV) acquisition and HPV-associated diseases. This study set out to determine whether a two-dose (2D) HPV vaccination schedule was sufficient in HIV-infected adolescents with immune reconstitution (IR) following antiretroviral treatment. Participants aged 9–15 years who had CD4 cell counts > 500 cells/mm3 and HIV-1 RNA p = 0.946), respectively, and the anti-HPV-18 GMTs were 2039.3 (1432.2–2903.8) and 2859.8 (1810.0–4518.4) in the 2D and 3D (p = 0.313) groups, respectively. In females, the anti-HPV-16 GMTs were 15,758.7 (8868.0–28,003.4) and 26,241.6 (16,972.7–40,572.3) in the 2D and 3D groups (p = 0.197), respectively, and the anti-HPV-18 GMTs were 5971.4 (3026.8–11,780.6) and 9993.1 (5950.8–16,781.1) in the 2D and 3D groups (p = 0.271), respectively. In summary, a 2D schedule is as immunogenic in young adolescents with IR as a 3D schedule in older subjects and those without IR

Immunogenicity and reactogenicity of heterologous COVID-19 vaccination in pregnant women

This open-labeled non-inferiority trial evaluated immunogenicity and reactogenicity of heterologous and homologous COVID-19 vaccination schedules in pregnant Thai women. 18–45-year-old pregnant women with no history of COVID-19 infection or vaccination and a gestational age of ≥12 weeks were randomized 1:1:1 into three two-dose primary series scheduled 4 weeks apart: BNT162b2-BNT162b2 (Group 1), ChAdOx1-BNT162b2 (Group 2), and CoronaVac-BNT162b2 (Group 3). Serum antibody responses, maternal and cord blood antibody levels at delivery, and adverse events (AEs) following vaccination until delivery were assessed. The 124 enrolled participants had a median age of 31 (interquartile range [IQR] 26.0–35.5) years and gestational age of 23.5 (IQR 18.0–30.0) weeks. No significant difference in anti-receptor binding domain (RBD) IgG were observed across arms at 2 weeks after the second dose. Neutralizing antibody geometric mean titers against the ancestral Wuhan strain were highest in Group 3 (258.22, 95% CI [187.53, 355.56]), followed by Groups 1 (187.47, 95% CI [135.15, 260.03]) and 2 (166.63, 95% CI [124.60, 222.84]). Cord blood anti-RBD IgG was correlated with, and equal to or higher than, maternal levels at delivery (r = 0.719, P < .001) and inversely correlated with elapsed time after the second vaccination (r = −0.366, P < .001). No significant difference in cord blood antibody levels between groups were observed. Local and systemic AEs were mild-to-moderate and more frequent in Group 2. Heterologous schedules of CoronaVac-BNT162b2 or ChAdOx1-BNT162b2 induced immunogenicity on-par with BNT162b2-BNT162b2 and may be considered as alternative schedules for primary series in pregnant women in mRNA-limited vaccine settings

Study profile.

IntroductionThere are gaps in knowledge and experience of antiretroviral pre-exposure prophylaxis (PrEP) delivery in adolescents.MethodsThis pilot study enrolled Thai adolescents 14–20 year-old without HIV who reported risk behaviour. All participants were offered daily tenofovir/emtricitabine (TDF-FTC) and followed for 24 weeks. HIV testing, renal function, bone density scan, and sexually transmitted infection (STI) testing including syphilis serology and urine molecular testing for gonorrhoea and C. trachomatis were performed at baseline and weeks 12 and 24. Adherence was evaluated through intracellular tenofovir diphosphate (TFV-DP) levels in dried blood spots.ResultsOf the 61 enrolled adolescents, median age 18.1 (IQR: 14.8–20.9) years, 46 (75.4%) were males and 36 (59%) were MSM. Retention to week 24 was 80.3%. One third (36%) had TFV-DP levels consistent with taking ≥6 pills/week at week 12 and 29% at week 24. The factors associated with taking ≥6 pills/week were being MSM (adjusted odds ratio [aOR]: 53.2, 95% CI: 1.6–1811; p = 0.027), presence of STI at baseline (aOR: 9.4, 95% CI: 1.5–58.5; p = 0.016), and self-report of decreased condom use while taking PrEP (aOR: 8.7, 95% CI: 1.4–56.6; p = 0.023). 31% had an STI at baseline and this declined to 18% at week 24. No renal or bone toxicity was observed and there were no HIV seroconversions.ConclusionsDaily oral PrEP with FTC-TDF in high-risk Thai adolescents is feasible, accepted, well-tolerated, and had no increased risk compensation; however, low adherence was a major challenge. Adolescent-specific PrEP strategies including long-acting modalities are needed for successful HIV prevention.</div

Self-reported adverse events in adolescents while taking tenofovir disoproxil fumarate-emtricitabine for pre-exposure prophylaxis.

Self-reported adverse events in adolescents while taking tenofovir disoproxil fumarate-emtricitabine for pre-exposure prophylaxis.</p