BACKGROUND Although both maternal respiratory syncytial virus (RSV) prefusion F vaccination (RSVpreF) and infant nirsevimab immunization have been approved for the prevention of RSV lower respiratory tract infections, the 2 have not been evaluated in a single study, and their sequential administration has not been studied systematically. METHODS We performed a prospective, randomized, open-label, phase 4 study at 8 US sites of mother-infant pairs randomized 1:1:1:1 during pregnancy: maternal RSVpreF vaccine alone, maternal RSVpreF vaccine/infant nirsevimab at birth, maternal RSVpreF vaccine/infant nirsevimab at 3 months, or infant nirsevimab alone at birth. We are following the mother-infant pairs for 12 months to ascertain safety, infant tolerability, and the magnitude and durability of RSV-A and -B neutralizing antibodies (nAbs). We report interim data from September 19, 2024, to May 15, 2025, including 4-month infant follow-up. RESULTS In total, 181 mothers were enrolled. Both products alone and in combination were safe. No related serious adverse events were observed in mothers or infants. Nirsevimab was well tolerated, and all local and systemic reactogenicity was mild to moderate in severity. RSVpreF vaccination boosted maternal RSV-A nAb titers 17.35-fold at the time of delivery, and titers were durable through 3 months postdelivery. The geometric mean transfer ratio of RSV-A nAbs was higher than 1.3 and similar across groups. RSV nAbs were highly elevated in infants at 6 weeks and 3 months, irrespective of group, with modest differences in waning. CONCLUSIONS Maternal RSVpreF vaccine and infant nirsevimab administration, either alone or in combination, were safe and provided high RSV nAb titers in infants through interim follow-up.

A quadrivalent meningococcal tetanus toxoid-conjugate vaccine, MenACYW-TT, has been developed to provide protection against invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y, and W. This Phase 3 study (NCT03537508; April 25, 2018, to September 22, 2023) evaluated the immunogenicity and safety of MenACYW-TT, compared with a licensed quadrivalent meningococcal oligosaccharide diphtheria CRM197-conjugate vaccine (MenACWY-CRM), in healthy infants ≥6 weeks of age when administered concomitantly with routine pediatric vaccines in a four-dose series (3 + 1 schedule). Functional antibodies against each meningococcal serogroup were measured by serum bactericidal antibody assay using human complement (hSBA). Non-inferiority was demonstrated for the first co-primary endpoint of seroresponse rates 30 days after the fourth dose at 12-15 months of age, with serogroup-specific seroresponse rates of 79.4%-97.6% and 77.6%-96.4% for MenACYW-TT and MenACWY-CRM, respectively. Non-inferiority was also demonstrated for the second co-primary endpoint based on proportions of participants with hSBA antibody titers ≥1:8 against each serogroup 30 days after the third dose at 6 months of age, with rates of 77.9-99.0% for MenACYW-TT and 67.7-92.9% for MenACWY-CRM. After four doses, hSBA geometric mean titers were comparable for serogroup A and higher for serogroups C, W, and Y with MenACYW-TT versus MenACWY-CRM. Immune responses to all routine pediatric vaccines administered concomitantly with MenACYW-TT were non-inferior to those following concomitant administration with MenACWY-CRM. MenACYW-TT and MenACWY-CRM were overall well tolerated, and the safety profiles of these vaccines were comparable. This study supports the use of MenACYW-TT in infants aged 6 weeks (42 days) or older.Study registration: ClinicalTrials.gov: NCT03537508.

BACKGROUND:Cell-mediated immunity (CMI) may help protect against emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that are less susceptible to neutralizing antibodies. We present CMI data after the mRNA-1273 primary series in a subset of participants aged 6 months to 11 years from the phase 2/3 KidCOVE trial. METHODS:T-cell responses were assessed after 2 doses of mRNA-1273 (6 months to 5 years, 25 μg; 6-11 years, 50 μg) or placebo administered 28 days apart. Magnitude, phenotype, and percentage of ancestral SARS-CoV-2 spike (S) protein T-cell responses to pooled peptides were assessed by intracellular cytokine staining and polyfunctionality analyses. RESULTS:A total of 68 children aged 6 months to 11 years received either the 2-dose mRNA-1273 primary series or placebo (51 and 17, respectively) at 28-day interval. mRNA-1273 induced S-protein-specific CD4+ T-cell responses exhibiting a type 1 T helper (Th1)-biased profile at day 43 and day 209 compared with placebo. S-protein-specific CD8+ T-cell responses were less frequently detected in children <5 years and undetectable in those <2 years. Compared with placebo, mRNA-1273 induced higher frequencies of S-specific polyfunctional CD4+ T cells at day 43; frequencies declined but remained detectable at day 209. Correlation between Th1 CD4+ responses and neutralizing antibodies was observed across age groups following mRNA-1273 vaccination. CONCLUSIONS:The 2-dose mRNA-1273 primary series elicited robust and durable (≥ 6 months) Th1-biased CD4+ T-cell responses in children aged 6 months to 11 years. CD8+ T-cell responses varied by age. Clinical Trials Registration. NCT04796896.

The Advisory Committee on Immunization Practices, a group of medical and public health experts that provides advice to the Centers for Disease Control and Prevention, normally meets 3 times per year to develop US vaccine recommendations. The Advisory Committee on Immunization Practices met February 28 to 29, 2024, to discuss coronavirus disease 2019 vaccines, chikungunya vaccines, diphtheria-tetanus vaccine, influenza vaccines, polio vaccines, respiratory syncytial virus vaccines, meningococcal vaccines, pneumococcal vaccines, and Vaxelis (Diphtheria, Tetanus, Pertussis, Inactivated Poliovirus, Haemophilus influenzae b Conjugate, and Hepatitis B Vaccine). This update summarizes the proceedings of these meetings, with an emphasis on topics that are most relevant to the pediatric population. Major updates for pediatric clinicians include information about changes on influenza vaccine composition, meningococcal vaccination considerations, updated guidance for children with a contraindication to pertussis-containing vaccines, and recommendations of the world's first chikungunya vaccine for certain populations.

ABSTRACT Pertussis (whooping cough) is a reemergent, highly contagious respiratory infection of public health concern. Infants prior to initiation of their primary vaccination series are the most vulnerable to severe infection, and even death. Vaccination during pregnancy is an efficacious means of reducing infection in infants. This approach relies on boosting maternal immunity and passive transfer of antibodies to the infant via placenta and breast milk. Similarly, maternal vaccination post-partum can enhance maternal-infant immunity. To support the analysis of pertussis immunity in the context of maternal-infant immunization, we developed a high throughput multiplex assay for simultaneous quantification of serum IgG antibodies against pertussis vaccine antigens: pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), and fimbriae (FIM2/3), and against tetanus (TT) and diphtheria toxoids (DT), using the Meso Scale Discovery (MSD) platform. The assay was qualified, and specificity, sensitivity, accuracy, precision, linearity, and robustness were demonstrated. The assay was subsequently adapted for quantification of IgG and IgA in breast milk. Applied to a serological survey of pregnant women living in the United States and sub-Saharan Africa, this method revealed differences in magnitude and breadth of antibody profile, consistent with history of vaccination. A longitudinal analysis of Tdap responses in women vaccinated post-partum demonstrated a rapid increase in serum IgG that remained elevated for up to 24 months. Likewise, high levels of vaccine-specific IgA and IgG antibodies were present in breast milk, although they exhibited faster decay. This multiplex MSD assay is a reliable and practical tool for quantification of pertussis, tetanus, and diphtheria antibodies in serum and breast milk in serosurveys or vaccine studies. IMPORTANCE Pertussis (whooping cough) has reemerged in recent years. Vaccination during pregnancy is an effective approach to prevent illness during the first months of life. We developed a multiplex assay for quantification of pertussis, tetanus, and diphtheria serum antibodies using the Meso Scale Discovery (MSD) platform; the method was qualified, and specificity, precision, accuracy, linearity, and limits of quantification were defined. It was also adapted for quantification of antibodies in breast milk. We successfully determined serostatus in women from different regions and with different vaccination histories, as well as responses to Tdap in blood and breast milk post-partum. This is the first description of a multiplex assay for the quantification of pertussis, tetanus, and diphtheria antibodies in breast milk.

Background. Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in infants. This phase 1/2, observer-blind, randomized, controlled study assessed the safety and immunogenicity of an investigational chimpanzee-derived adenoviral vector RSV vaccine (ChAd155-RSV, expressing RSV F, N, and M2-1) in infants. Methods. Healthy 6- to 7-month-olds were 1:1:1-randomized to receive 1 low ChAd155-RSV dose (1.5 x 10(10) viral particles) followed by placebo (RSV_1D); 2 high ChAd155-RSV doses (5 x 10(10) viral particles) (RSV_2D); or active comparator vaccines/placebo (comparator) on days 1 and 31. Follow-up lasted approximately 2 years. Results. Two hundred one infants were vaccinated (RSV_1D: 65; RSV_2D: 71; comparator: 65); 159 were RSV-seronaive at baseline. Most solicited and unsolicited adverse events after ChAd155-RSV occurred at similar or lower rates than after active comparators. In infants who developed RSV infection, there was no evidence of vaccine-associated enhanced respiratory disease (VAERD). RSV-A neutralizing titers and RSV F-binding antibody concentrations were higher post-ChAd155-RSV than postcomparator at days 31, 61, and end of RSV season 1 (mean follow-up, 7 months). High-dose ChAd155-RSV induced stronger responses than low-dose, with further increases post-dose 2. Conclusions. ChAd155-RSV administered to 6- to 7-month-olds had a reactogenicity/safety profile like other childhood vaccines, showed no evidence of VAERD, and induced a humoral immune response.

OBJECTIVES: To investigate which independent factor(s) have an impact on the pharmacokinetics of vancomycin in critically ill children, develop an equation to predict the 24-hour area under the concentration-time curve from a trough concentration, and evaluate dosing regimens likely to achieve a 24-hour area under the concentration-time curve to minimum inhibitory concentration ratio (AUC24/MIC) greater than or equal to 400. DESIGN: Prospective population pharmacokinetic study of vancomycin. SETTING: Critically ill patients in quaternary care PICUs. PATIENTS: Children 90 days old or older to younger than 18 years who received IV vancomycin treatment, irrespective of the indication for use, in the ICUs at the University of Maryland Children’s Hospital and Texas Children’s Hospital were enrolled. INTERVENTIONS: Vancomycin was prescribed at doses and intervals chosen by the treating clinicians. MEASUREMENTS AND MAIN RESULTS: A median of four serum levels of vancomycin per patient were collected along with other variables for up to 7 days following the first administration. These data were used to characterize vancomycin pharmacokinetics and evaluate the factors affecting the variability in achieving AUC24/MIC ratio greater than or equal to 400 in PICU patients who are not on extracorporeal therapy. A total of 302 children with a median age of 6.0 years were enrolled. A two-compartment model described the pharmacokinetics of vancomycin with the clearance of 2.76 L/hr for a typical patient weighing 20 kg. The glomerular filtration rate estimated using either the bedside Schwartz equation or the chronic kidney disease in children equation was the only statistically significant predictor of clearance among the variables evaluated, exhibiting equal predictive performance. The trough levels achieving AUC24/MIC = 400 were 5.6–10.0 μg/mL when MIC = 1 μg/mL. The target of AUC24/MIC greater than or equal to 400 was achieved in 60.4% and 36.5% with the typical dosing regimens of 15 mg/kg every 6 and 8 hours (q6h and q8h), respectively. CONCLUSIONS: The pharmacokinetics of vancomycin in critically ill children were dependent on the estimated glomerular filtration rate only. Trough concentrations accurately predict AUC24. Typical pediatric vancomycin dosing regimens of 15 mg/kg q6h and q8h will often lead to AUC24/MIC under 400.

Ebola virus disease (EVD) is a filoviral infection caused by virus species of the Ebolavirus genus including Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV). We investigated the safety and immunogenicity of a heterologous prime-boost regimen involving a chimpanzee adenovirus 3 vectored Ebola vaccine [either monovalent (cAd3-EBOZ) or bivalent (cAd3-EBO)] prime followed by a recombinant modified vaccinia virus Ankara EBOV vaccine (MVA-EbolaZ) boost in two phase 1/1b randomized open-label clinical trials in healthy adults in the United States (US) and Uganda (UG). Trial US (NCT02408913) enrolled 140 participants, including 26 EVD vaccine-naïve and 114 cAd3-Ebola-experienced participants (April-November 2015). Trial UG (NCT02354404) enrolled 90 participants, including 60 EVD vaccine-naïve and 30 DNA Ebola vaccine-experienced participants (February-April 2015). All tested vaccines and regimens were safe and well tolerated with no serious adverse events reported related to study products. Solicited local and systemic reactogenicity was mostly mild to moderate in severity. The heterologous prime-boost regimen was immunogenic, including induction of durable antibody responses which peaked as early as two weeks and persisted up to one year after each vaccination. Different prime-boost intervals impacted the magnitude of humoral and cellular immune responses. The results from these studies demonstrate promising implications for use of these vaccines in both prophylactic and outbreak settings.

We conducted a single-center study at a free community testing site in Baltimore City to assess the accuracy of self-performed rapid antigen tests (RATs) for COVID-19. Self-administered BinaxNOW RATs were compared with clinician-performed RATs and against a reference lab molecular testing as the gold standard. Of the 953 participants, 14.9% were positive for SARS- CoV-2 as determined by RT-PCR. The sensitivity and specificity were similar for both self- and clinician-performed RATs (sensitivity: 83.9% vs 88.2%, P = 0.40; specificity: 99.8% vs 99.6%, P = 0.6). Subgroup comparisons based on age and race yielded similar results. Notably, 5.2% (95% CI: 1.5% to 9.5%) of positive results were potentially missed due to participant misinterpretation of the self-test card. However, the false-positive rate for RATs was reassuringly comparable in accuracy to clinician-administered tests. These findings hold significant implications for physicians prescribing treatment based on patient-reported, self-administered positive test results. Our study provides robust evidence supporting the reliability and utility of patient-performed RATs, underscoring their comparable accuracy to clinician-performed RATs, and endorsing their continued use in managing COVID-19. Further studies using other rapid antigen test brands are warranted.IMPORTANCEAccurate and accessible COVID-19 testing is crucial for effective disease control and management. A recent single-center study conducted in Baltimore City examined the reliability of self-performed rapid antigen tests (RATs) for COVID-19. The study found that self-administered RATs yielded similar sensitivity and specificity to clinician-performed tests, demonstrating their comparable accuracy. These findings hold significant implications for physicians relying on patient-reported positive test results for treatment decisions. The study provides robust evidence supporting the reliability and utility of patient-performed RATs, endorsing their continued use in managing COVID-19. Furthermore, the study highlights the need for further research using different rapid antigen test brands to enhance generalizability. Ensuring affordable and widespread access to self-tests is crucial, particularly in preparation for future respiratory virus seasons and potential waves of reinfection of SARS-CoV-2 variants such as the Omicron variant.

IMPORTANCE Greater than 20% of cases and 0.4% of deaths from COVID-19 occur in children. Following demonstration of the safety and efficacy of the adjuvanted, recombinant spike protein vaccine NVX-CoV2373 in adults, the PREVENT-19 trial immediately expanded to adolescents. OBJECTIVE To evaluate the safety, immunogenicity, and efficacy of NVX-CoV2373 in adolescents. DESIGN, SETTING, AND PARTICIPANTS The NVX-CoV2373 vaccine was evaluated in adolescents aged 12 to 17 years in an expansion of PREVENT-19, a phase 3, randomized, observer-blinded, placebo-controlled multicenter clinical trial in the US. Participants were enrolled from April 26 to June 5, 2021, and the study is ongoing. A blinded crossover was implemented after 2 months of safety follow-up to offer active vaccine to all participants. Key exclusion criteria included known previous laboratory-confirmed SARS-CoV-2 infection or known immunosuppression. Of 2304 participants assessed for eligibility, 57 were excluded and 2247 were randomized. INTERVENTIONS Participants were randomized 2:1 to 2 intramuscular injections of NVX-CoV2373 or placebo, 21 days apart. MAIN OUTCOMES AND MEASURES Serologic noninferiority of neutralizing antibody responses compared with those in young adults (aged 18–25 years) in PREVENT-19, protective efficacy against laboratory-confirmed COVID-19, and assessment of reactogenicity and safety. RESULTS Among 2232 participants (1487 NVX-CoV2373 and 745 placebo recipients), the mean (SD) age was 13.8 (1.4) years, 1172 (52.5%) were male, 1660 (74.4%) were White individuals, and 359 (16.1%) had had a previous SARS-CoV-2 infection at baseline. After vaccination, the ratio of neutralizing antibody geometric mean titers in adolescents compared with those in young adults was 1.5 (95% CI, 1.3–1.7). Twenty mild COVID-19 cases occurred after a median of 64 (IQR, 57–69) days of follow-up, including 6 among NVX-CoV2373 recipients (incidence, 2.90 [95% CI, 1.31–6.46] cases per 100 person-years) and 14 among placebo recipients (incidence, 14.20 [95% CI, 8.42–23.93] cases per 100 person-years), yielding a vaccine efficacy of 79.5% (95% CI, 46.8%−92.1%). Vaccine efficacy for the Delta variant (the only viral variant identified by sequencing [n = 11]) was 82.0% (95% CI, 32.4%−95.2%). Reactogenicity was largely mild to moderate and transient, with a trend toward greater frequency after the second dose of NVX-CoV2373. Serious adverse events were rare and balanced between treatments. No adverse events led to study discontinuation. CONCLUSIONS AND RELEVANCE The findings of this randomized clinical trial indicate that NVX-CoV2373 is safe, immunogenic, and efficacious in preventing COVID-19, including the predominant Delta variant, in adolescents. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04611802

Respiratory syncytial virus (RSV) is the most common cause of early childhood lower respiratory tract infection (LRTI) in low- and middle-income countries (LMICs). Maternal vaccines, birth-dose extended half-life monoclonal antibodies (mAbs), and pediatric vaccines are under development for prevention of respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) in young children. We analyzed the health and economic impact of RSV interventions used alone or in combinations in Mali. We modeled age-specific and season-specific risks of RSV LRTI in children through three years, using WHO Preferred Product Characteristics and data generated in Mali. Health outcomes included RSV LRTI cases, hospitalizations, deaths, and disability-adjusted life-years (DALYs). We identified the optimal combination of products across a range of scenarios. We found that mAb delivered at birth could avert 878 DALYs per birth cohort at an incremental cost-effectiveness ratio (ICER) of $597 per DALY averted compared to no intervention if the product were available at $1 per dose. Combining mAb with pediatric vaccine administered at 10/14 weeks, 1947 DALYs would be prevented. The ICER of this combination strategy is $1514 per DALY averted compared to mAb alone. Incorporating parameter uncertainty, mAb alone is likely to be optimal from the societal perspective at efficacy against RSV LRTI above 66%. The optimal strategy was sensitive to economic considerations, including product prices and willingness-to-pay for DALYs. For example, the combination of mAb and pediatric vaccine would be optimal from the government perspective at a willingness-to-pay above $775 per DALY. Maternal vaccine alone or in combination with other interventions was never the optimal strategy, even for high vaccine efficacy. The same was true for pediatric vaccine administered at 6/7 months. At prices comparable to existing vaccine products, extended half-life RSV mAbs would be impactful and efficient components of prevention strategies in LMICs such as Mali.

Background Although there have been many studies on antibody responses to SARS-CoV-2 in breast milk, very few have looked at the fate of these in the infant, and whether they are delivered to immunologically relevant sites in infants. Methods Mother/infant pairs (mothers who breast milk fed and who were SARS-CoV-2 vaccinated before or after delivery) were recruited for this cross-sectional study. Mother blood, mother breast milk, infant blood, infant nasal specimen, and infant stool was tested for IgA and IgG antibodies against SARS-CoV-2 spike trimer. Results Thirty-one mother/infant pairs were recruited. Breast milk fed infants acquired systemic anti-spike IgG antibodies only if their mothers were vaccinated antepartum (100% Antepartum; 0% Postpartum; P<0.0001). Breast milk fed infants acquired mucosal anti-spike IgG antibodies (in the nose) only if their mothers were vaccinated antepartum (89% Antepartum; 0% Postpartum; P<0.0001). None of the infants in either group had anti-spike IgA in the blood. Surprisingly, 33% of the infants whose mothers were vaccinated antepartum had high titer anti-spike IgA in the nose (33% Antepartum; 0% Postpartum; P = 0.03). Half-life of maternally transferred plasma IgG antibodies in the Antepartum infant cohort was ~70 days. Conclusion Vaccination antepartum followed by breast milk feeding appears to be the best way to provide systemic and local anti-SARS-CoV-2 antibodies for infants. The presence of high titer SARS-CoV-2-specific IgA in the nose of infants points to the potential importance of breast milk feeding early in life for maternal transfer of mucosal IgA antibodies. Expectant mothers should consider becoming vaccinated antepartum and consider breast milk feeding for optimal transfer of systemic and mucosal antibodies to their infants.

Abstract Background Little is known about parental awareness of multisystem inflammatory syndrome in children (MIS-C), a rare but severe sequela of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods Via a nationally representative, cross-sectional survey of US parents conducted via Ipsos KnowledgePanel from October to November 2021, we used bivariate and multivariable analyses to describe and identify demographic variables associated with parental knowledge of and attitudes toward MIS-C and to examine associations with perceived coronavirus disease 2019 (COVID-19) severity and susceptibility. Results Response rate was 64.2% (3230/5034). Thirty-two percent of respondents had heard of MIS-C. After adjustment, higher educational level (compared to high school degree; some college: odds ratio [OR], 2.00 [95% confidence interval {CI}, 1.44–2.77]; bachelor's degree or higher: OR, 3.14 [95% CI, 2.26–4.35]), being a healthcare worker (OR, 1.82 [95% CI, 1.37–2.42]), having a child with a chronic medical condition (OR, 1.62 [95% CI, 1.22–2.14]), and experience with more severe COVID-19 (OR, 1.46 [95% CI, 1.14–1.86]) were associated with MIS-C awareness. Respondents with a child aged 12–17 years were less likely to be aware of MIS-C compared to those without (OR, 0.78 [95% CI, .63–.96]), as were male respondents (OR, 0.56 [95% CI, .46–.69]) and respondents aged 18–34 years (OR, 0.72 [95% CI, .54–.94]) compared to those aged 35–44 years. Awareness of MIS-C was associated with higher perceived COVID-19 severity and susceptibility (regression coefficients, 0.18 [95% CI, .10–.25], P < .001; 0.19 [95% CI, .11–.28], P < .001, respectively). Conclusions This survey highlights the need to increase parental awareness of MIS-C. Future studies should explore how education regarding MIS-C as a complication of SARS-CoV-2 infection could improve understanding of pediatric disease severity and susceptibility.

Abstract Background Vaccination of children to prevent coronavirus disease 2019 (Covid-19) is an urgent public health need. The safety, immunogenicity, and efficacy of the mRNA-1273 vaccine in children 6 to 11 years of age are unknown. Methods Part 1 of this ongoing phase 2–3 trial was open label for dose selection; part 2 was an observer-blinded, placebo-controlled expansion evaluation of the selected dose. In part 2, we randomly assigned children (6 to 11 years of age) in a 3:1 ratio to receive two injections of mRNA-1273 (50 μg each) or placebo, administered 28 days apart. The primary objectives were evaluation of the safety of the vaccine in children and the noninferiority of the immune response in these children to that in young adults (18 to 25 years of age) in a related phase 3 trial. Secondary objectives included determination of the incidences of confirmed Covid-19 and severe acute respiratory syndrome coronavirus 2 infection, regardless of symptoms. Interim analysis results are reported. Results In part 1 of the trial, 751 children received 50-μg or 100-μg injections of the mRNA-1273 vaccine, and on the basis of safety and immunogenicity results, the 50-μg dose level was selected for part 2. In part 2 of the trial, 4016 children were randomly assigned to receive two injections of mRNA-1273 (50 μg each) or placebo and were followed for a median of 82 days (interquartile range, 14 to 94) after the first injection. This dose level was associated with mainly low-grade, transient adverse events, most commonly injection-site pain, headache, and fatigue. No vaccine-related serious adverse events, multisystem inflammatory syndrome in children, myocarditis, or pericarditis were reported as of the data-cutoff date. One month after the second injection (day 57), the neutralizing antibody titer in children who received mRNA-1273 at a 50-μg level was 1610 (95% confidence interval [CI], 1457 to 1780), as compared with 1300 (95% CI, 1171 to 1443) at the 100-μg level in young adults, with serologic responses in at least 99.0% of the participants in both age groups, findings that met the prespecified noninferiority success criterion. Estimated vaccine efficacy was 88.0% (95% CI, 70.0 to 95.8) against Covid-19 occurring 14 days or more after the first injection, at a time when B.1.617.2 (delta) was the dominant circulating variant. Conclusions Two 50-μg doses of the mRNA-1273 vaccine were found to be safe and effective in inducing immune responses and preventing Covid-19 in children 6 to 11 years of age; these responses were noninferior to those in young adults. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; KidCOVE ClinicalTrials.gov number, NCT04796896.)

Pregnancy represents a unique tolerogenic immune state which may alter susceptibility to infection and vaccine response. Here, we characterized humoral immunity to seasonal influenza vaccine strains in pregnant and non-pregnant women. Although serological responses to influenza remained largely intact during late pregnancy, distinct modifications were observed. Pregnant women had reduced hemagglutinin subtype-1 (H1)- IgG, IgG1, IgG2, and IgG3, hemagglutination inhibition, and group 1 and 2 stem IgG titers. Intriguingly, H1-specific avidity and FcγR1 binding increased, and influenza antibodies had distinct Fc and Fab glycans characterized by increased di-galactosylation and di-sialylation. H1-specific Fc-functionality (i.e. monocyte phagocytosis and complement deposition) was moderately reduced in pregnancy. Multivariate antibody analysis revealed two distinct populations (pregnant vs. non-pregnant) segregated by H1 FcγR1 binding, H1-IgG levels, and Fab and Fc glycosylation. Our results demonstrated a structural and functional modulation of influenza humoral immunity during pregnancy that was antigen-specific and consistent with reduced inflammation and efficient placental transport.

Abstract Background Little was known about US parental attitudes, beliefs, and intentions surrounding coronavirus disease 2019 (COVID-19) vaccines for children before their introduction. Methods An online cross-sectional nationally representative survey of US parents/guardians of children < 18 years old via Ipsos KnowledgePanel, fielded from October 26, 2021 to November 30, 2021. Results Response rate was 64.2% (3230/5034). For children ages 0–4 years, 51.5% of parents were likely to have their children vaccinated, and for ages 5–11 and 12–17, 54.0% and 69.7% of parents, respectively, reported they were likely to vaccinate or had already vaccinated their children. Among respondents with unvaccinated children, 25.2% (ages 0–4) and 22.0% (ages 5–11) reported they would seek COVID-19 vaccination for their children as soon as authorization occurred. Factors associated with willingness to have children receive a COVID-19 vaccine were: belief in benefits of COVID-19 vaccination (odds ratio [OR] = 6.44, 5.68, 4.57 in ages 0–4, 5–11, and 12–17 respectively), acceptance of routine childhood vaccines (OR = 6.42, 5.48, 1.76), parental COVID-19 vaccination (OR = 1.85, 3.70, 6.16), perceptions that pediatric COVID-19 is severe (OR = 1.89, 1.72, 1.35), Hispanic ethnicity (OR = 2.07, 2.29, 2.60), influenza vaccine acceptance (OR = 1.07, 0.88, 1.62), presence of children of another age group in the household (OR = 0.71, 0.71, 0.65), and attitudinal barriers to COVID-19 vaccination (OR = 0.30, 0.26, 0.49). Conclusions Belief in the benefits of COVID-19 vaccination and acceptance of routine childhood vaccines are the strongest predictors of intention to vaccinate children. Further research is needed to track how parental attitudes change as more data about pediatric COVID-19 vaccines become available and how intentions translate into pediatric vaccine uptake.

The World Health Organization recommends universal vaccination of medically stable infants with Hepatitis B vaccine within 24 hours of birth to prevent mother-to-child transmission of Hepatitis B virus (HBV) infection. However, the proportion of infants who receive a timely birth dose is extremely low in Nigeria. We reviewed the implementation of an infant HBV vaccine schedule at a single center and identified factors affecting the receipt of a timely birth dose of HBV vaccine. We conducted a retrospective cohort study utilizing data from the INFANT study, a 2013-2017 prospective cohort study of pregnant women with and without HIV and their infants We utilized bivariate and multivariable logistic regression to assess if maternal characteristics, or the day of the week on which the infant was born were significantly associated with timely receipt of a birth dose of HBV vaccine. Receipt of HBV vaccine on the day of birth or the following calendar day were considered a timely birth dose. Among 409 infants in our cohort, 133 infants (33%) received a timely birth dose of HBV vaccine. Only the day of the week on which infants were born was significant (p<0.0001): when compared to Friday, infants born Monday through Thursday had significantly higher odds of receiving a timely birth dose, while infants born on a Saturday or Sunday had similar (low) odds. We found no association between maternal age, education, marital status, HIV status, parity and mode of delivery, and infant receipt of a timely birth dose of HBV vaccine. National immunization programs could improve timely HBV birth dose rates by providing access to vaccine immediately following birth at all infant delivery venues on all days of the week. Where not possible, there should be rapid linkage to the nearest facility where HBV vaccination is immediately available.

Early in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, before coronavirus disease-2019 (COVID-19) vaccines were authorized, surveys began tracking public acceptance of a hypothetical COVID-19 vaccine. As vaccines became more widely available, the focus shifted from evaluating premeditative thoughts about COVID-19 vaccines to observing behaviors, measuring uptake, and characterizing factors associated with acceptance. A wealth of peer-reviewed literature examining the complexities of COVID-19 vaccine acceptance has emerged, but our understanding of COVID-19 vaccine acceptance is constantly evolving. In this article, we review the current state of knowledge regarding COVID-19 vaccine hesitancy, with an emphasis on pediatric vaccination.

SARS-CoV-2 continues to develop new, increasingly infectious variants including delta and omicron. We evaluated the efficacy of the Abbott BinaxNOW Rapid Antigen Test against Reverse Transcription PCR (RT-PCR) in 1,054 pediatric participants presenting to a high-volume Coronavirus Disease 2019 (COVID-19) testing site while the delta variant was predominant. Both tests utilized anterior nares swabs. Participants were grouped by COVID-19 exposure and symptom status. 5.2% of samples tested positive by RT-PCR for SARS-CoV-2. For all participants, sensitivity of the BinaxNOW was 92.7% (95% CI 82.4%-98.0%), and specificity was 98.0% (95% CI 97.0%-98.8%). For symptomatic participants, positive predictive value (PPV) was 72.7% (95% CI 54.5%-86.7%) and negative predictive value (NPV) was 99.2% (95% CI 98.2%-100%). Among asymptomatic participants, PPV was 71.4% (95% CI 53.7%-85.4%) and NPV was 99.7% (95% CI 99.0%-100%). Our reported sensitivity and NPV are higher than other pediatric studies, potentially because of higher viral load from the delta variant, but specificity and PPV are lower. IMPORTANCE The BinaxNOW rapid antigen COVID-19 test had a sensitivity of nearly 92% in both symptomatic and asymptomatic children when performed at a high-throughput setting during the more transmissible delta variant dominant period. The test may play an invaluable role in asymptomatic screening and keeping children safe in school.