A phase 3 randomized study to evaluate safety and immunogenicity of 20-valent pneumococcal conjugate vaccine in healthy Japanese infants.

OBJECTIVES: Safety and immunogenicity evaluation of a 4-dose series with 20-valent pneumococcal conjugate vaccine (PCV20). METHODS: This phase 3, double-blind study randomized healthy Japanese infants to receive 4 doses (3 infant doses, 1 toddler dose) of PCV20 by subcutaneous (SC) or intramuscular (IM) injection or 13-valent PCV (PCV13) SC. A primary immunogenicity objective was to demonstrate noninferiority of PCV20 SC to PCV13 SC for percentages of participants meeting predefined serotype-specific immunoglobulin G concentrations 1 month after Dose 3. The 7 additional PCV20 serotypes were compared with the lowest vaccine serotype result in the PCV13 group. Safety and tolerability were assessed as the primary safety objective. RESULTS: Overall, 668 participants were randomized (PCV20 SC, n = 226; PCV13 SC, n = 224; PCV20 IM, n = 218). The primary noninferiority objective for PCV20 SC to PCV13 SC was met for 11/13 matched and 5/7 additional serotypes. Additional data showed PCV20 SC and IM elicited robust functional opsonophagocytic activity and boosting responses to all 20 vaccine serotypes. PCV20 had a similar safety/tolerability profile to PCV13, although local reactions were less frequent with PCV20 IM. CONCLUSIONS: A 4-dose series of PCV20 SC or IM elicited immune responses expected to be protective against all 20 serotypes in Japanese infants. NCT04530838.

Safety and immunogenicity of a 15-valent pneumococcal conjugate vaccine in Japanese healthy infants: A Phase I study (V114-028).

This Phase I study evaluated the safety, tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine (PCV), via subcutaneous (SC) or intramuscular (IM) administration, in healthy Japanese infants 3 months of age. A total of 133 participants were randomized to receive four doses (3 + 1 regimen) of V114-SC (n = 44), V114-IM (n = 45), or 13-valent PCV (PCV13)-SC (n = 44) at 3, 4, 5, and 12-15 months of age. Diphtheria, tetanus, and pertussis-inactivated poliovirus (DTaP-IPV) vaccine was administered concomitantly at all vaccination visits. The primary objective was to assess the safety and tolerability of V114-SC and V114-IM. Secondary objectives were to assess the immunogenicity of PCV and DTaP-IPV at 1-month post-dose 3 (PD3). On days 1-14 following each vaccination, the proportions of participants with systemic adverse events (AEs) were comparable across interventions, whereas injection-site AEs were higher with V114-SC (100.0%) and PCV13-SC (100.0%) than with V114-IM (88.9%). Most AEs were mild or moderate in severity and no vaccine-related serious AEs or deaths were reported. Serotype-specific immunoglobulin G (IgG) response rates at 1-month PD3 were comparable across groups for most shared serotypes between V114 and PCV13. For additional V114 serotypes 22F and 33F, IgG response rates were higher with V114-SC and V114-IM than with PCV13-SC. DTaP-IPV antibody response rates at 1-month PD3 for V114-SC and V114-IM were comparable with PCV13-SC. Findings suggest that vaccination with V114-SC or V114-IM in healthy Japanese infants is generally well tolerated and immunogenic.

Incontinentia pigmenti inherited from a father with a low level atypical IKBKG deletion mosaicism: a case report.

BACKGROUND: Incontinentia pigmenti (IP) is an X-liked dominant genodermatosis caused by mutations of the IKBKG/NEMO gene. IP is mostly lethal in males in utero, and only very rare male cases with a somatic mosaic mutation or a 47,XXY karyotype have been reported. CASE PRESENTATION: We here report a case of an IKBKG gene deletion in a female infant presenting with a few blisters and erythema in her upper arms at birth. MLPA analysis revealed a rare 94 kb deletion in this patient, encompassing the IKBKG gene and IKBKGP pseudogene. PCR analysis indicated the presence of Alu elements at both ends of the deletion, suggesting non-allelic homologous recombination as an underlying mechanism. Notably, a low-level mosaic deletion was identified in her father's peripheral blood leukocytes by PCR, suggesting a rare father-to-daughter transmission of IP. CONCLUSION: In family studies for an apparently sporadic IP case, parental analysis that includes the father is recommended due to the possibility of male mosaicism.

Cesarean section predominantly affects right ventricular diastolic function during the early transitional period.

BACKGROUND: Although the mode of delivery is well known to affect pulmonary function, the effects of a cesarean delivery on postnatal changes in cardiac mechanics have not been clearly defined. METHODS: To evaluate whether delivery mode influences cardiac function in the early transitional period, 42 infants delivered by cesarean section (CS) and 110 by vaginal delivery (VD) were enrolled, and they underwent serial echocardiography at 0, 1, 2, and 5 days of age. Longitudinal changes in ejection fraction (EF), fractional area change (FAC), mitral annular plane systolic excursion (MAPSE), tricuspid annular plane systolic excursion (TAPSE), Tei index, ratio of peak early diastolic flow velocity (E) to peak early diastolic annular velocity (e') (E/e'), and deceleration time (DcT) were compared between the two groups. RESULTS: FAC and DcT of both ventricles increased during the first week, whereas Tei index of each chamber decreased irrespective of delivery mode. E/e's of both ventricles were significantly higher and MAPSE was significantly lower in the CS than VD group throughout the observation period. After adjustment for the effects of birth weight, gestational age, and oxygen administration by multivariate analysis, right ventricular E/e', which reflects diastolic function of the right ventricle, was most affected by delivery mode. CONCLUSION: CS affected diastolic function of the right ventricle in the 2nd day after giving birth and did not persist. Delayed adaptation of the neonatal myocardium and/or persistence of pulmonary hypertension might explain the hemodynamic changes in neonates born by CS.

Prevalence of inhaled antigen sensitization and nasal eosinophils in Japanese children under two years old.

OBJECTIVE: The increasingly younger age of onset of allergic rhinitis (AR) has recently become a problem. This study examined the prevalence of inhaled antigen sensitization and nasal eosinophils in children younger than two years old, with measurement of the serum concentrations of aeroallergen-specific IgE antibodies to house dust mites, cat fur, and Japanese cedar pollen, measurement of nasal eosinophil counts, and a questionnaire administered to the children's parents. METHODS: The subjects were a group of healthy children undergoing 18-month infant health checks provided by the local government, and sick children younger than two years old at the pediatric hospital. RESULTS: Among 408 healthy infants, 44 (10.7%) had antigen-specific IgE antibodies, 29 (7.1%) had nasal eosinophils, and eight (2.0%) had both specific IgE antibodies and nasal eosinophils. Nasal assessment revealed that 125 children had rhinorrhea. Of the infants who showed both sensitization to antigens and nasal eosinophils, six (1.5%) had confirmed rhinorrhea. Among 186 sick children younger than two years old at the pediatric hospital, aeroallergen-specific IgE antibodies were detected in five (2.6%). The presence of nasal eosinophils was confirmed in six children (3.2%), which percentage was smaller than that of the healthy group. No infant had either sensitization to antigens or nasal eosinophils. CONCLUSION: The findings described above indicate that the minimum prevalence of AR might be 1.5% in 18-month-old children and that around 10% of affected children have aeroallergen-specific IgE antibodies in Japan. The incidence of AR in young children might increase further.

Hematopoietic contribution to skeletal muscle regeneration in acid alpha-glucosidase knockout mice.

Recent studies have shown that cells from bone marrow (BM) can give rise to differentiated skeletal muscle fibers. However, the mechanisms and identities of the cell types involved remain unknown. We performed BM transplantation in acid alpha-glucosidase (GAA) knockout mice, a model of glycogen storage disease type II, and our observations suggested that the BM cells contribute to skeletal muscle fiber formation. Furthermore, we showed that most CD45+:Sca1+ cells have a donor character in regenerating muscle of recipient mice. Based on these findings, CD45+:Sca1+ cells were sorted from regenerating muscles. The cell number was increased with granulocyte colony-stimulating factor after cardiotoxin injury, and the cells were transplanted directly into the tibialis anterior (TA) muscles of GAA knockout mice. Sections of the TA muscles stained with anti-laminin-alpha2 antibody showed that the number of CD45+:Sca1+ cells contributing to muscle fiber formation and glycogen levels were decreased in transplanted muscles. Our results indicated that hematopoietic stem cells, such as CD45+:Sca1+ cells, are involved in skeletal muscle regeneration.

The relationship in Japanese infants between a genetic polymorphism in the promoter region of the insulin-like growth factor I gene and the plasma level.

BACKGROUND: Evidence is accumulating that the promoter region of the insulin-like growth factor I (IGF-I) gene polymorphism and low levels of IGF-I are associated with type 2 diabetes, cardiovascular disease and birth weight; however, the number of wild-type alleles is different in each country. OBJECTIVES: This study aimed to examine the 737/738 marker, a cytosine-adenine repeat in the promoter region of the IGF-I gene polymorphism, and plasma IGF-I levels in Japanese infants and analyze the genetic background. METHODS: Data were collected for 15 months in Kyoto Prefectural University of Medicine. The body composition parameters of all infants were determined at birth. At 5 days after birth, we took blood samples to measure the product size of the promoter region of the IGF-I gene polymorphism and plasma IGF-I. RESULTS: In a population-based sample of 160 subjects, 6 different alleles and 16 genotypes were identified in the promoter region of the IGF-I gene polymorphism. The existence of a 196-bp allele has proved to result in a low plasma IGF-I level, a small head and chest circumference (p < 0.05) and no significant for premature birth, short-birth height and low-birth weight. CONCLUSIONS: This is the first study showing the role of the promoter region of the IGF-I gene polymorphism and the level of plasma IGF-I and body composition parameters in Japanese infants. Our results suggest genetical influence on prenatal growth and serum IGF-I levels.

Nutrient-enriched Diet in the Early Neonatal Period Influences the 3†year-old Height in Very Low Birth Weight Infants.

Nutrient-enriched milk has been advocated to enhance premature infants'growth and early nutritional intervention is effective for growth failure in very low birth weight infants (VLBWI). We studied the 3-yr-old physical growth of VLBWI who received nutrient enriched diets in the early neonatal period. VLBWI, who were born in 1996, received nutrient enriched milk around 1 mo of age. By contrast, in VLBWI born in 1998, nutrient enriched milk was started at 1-2 wk after birth. The daily calorie intake of VLBWI in 1998 had a tendency to be high compared to that of VLBWI in 1996. Height and body weight SD of 3-yr-old children who were born in 1998 tended to be greater than those of children who were born in 1996 (mean ± SD, -0.27 ± 0.54 vs. -1.01 ± 0.67; p=0.043, -0.47 ± 0.61 vs. -0.97 ± 1.10; p=0.31). Our study suggests that early feeding of nutrient-enriched milk for VLBWI in the neonatal period may affect their growth.