Live-Attenuated Respiratory Syncytial Virus Vaccine With M2-2 Deletion and With Small Hydrophobic Noncoding Region Is Highly Immunogenic in Children.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading viral cause of severe pediatric respiratory illness, and vaccines are needed. Live RSV vaccine D46/NS2/N/ΔM2-2-HindIII, attenuated by deletion of the RSV RNA regulatory protein M2-2, is based on previous candidate LID/ΔM2-2 but incorporates prominent differences from MEDI/ΔM2-2, which was more restricted in replication in phase 1. METHODS: RSV-seronegative children aged 6-24 months received 1 intranasal dose (105 plaque-forming units [PFUs] of D46/NS2/N/ΔM2-2-HindIII [n = 21] or placebo [n = 11]) and were monitored for vaccine shedding, reactogenicity, RSV-antibody responses and RSV-associated medically attended acute respiratory illness (RSV-MAARI) and antibody responses during the following RSV season. RESULTS: All 21 vaccinees were infected with vaccine; 20 (95%) shed vaccine (median peak titer, 3.5 log10 PFUs/mL with immunoplaque assay and 6.1 log10 copies/mL with polymerase chain reaction). Serum RSV-neutralizing antibodies and anti-RSV fusion immunoglobulin G increased ≥4-fold in 95% and 100% of vaccines, respectively. Mild upper respiratory tract symptoms and/or fever occurred in vaccinees (76%) and placebo recipients (18%). Over the RSV season, RSV-MAARI occurred in 2 vaccinees and 4 placebo recipients. Three vaccinees had ≥4-fold increases in serum RSV-neutralizing antibody titers after the RSV season without RSV-MAARI. CONCLUSIONS: D46/NS2/N/ΔM2-2-HindIII had excellent infectivity and immunogenicity and primed vaccine recipients for anamnestic responses, encouraging further evaluation of this attenuation strategy. CLINICAL TRIALS REGISTRATION: NCT03102034 and NCT03099291.

Live Respiratory Syncytial Virus Attenuated by M2-2 Deletion and Stabilized Temperature Sensitivity Mutation 1030s Is a Promising Vaccine Candidate in Children.

BACKGROUND: The safety and immunogenicity of live respiratory syncytial virus (RSV) candidate vaccine, LID/ΔM2-2/1030s, with deletion of RSV ribonucleic acid synthesis regulatory protein M2-2 and genetically stabilized temperature-sensitivity mutation 1030s in the RSV polymerase protein was evaluated in RSV-seronegative children. METHODS: Respiratory syncytial virus-seronegative children ages 6-24 months received 1 intranasal dose of 105 plaque-forming units (PFU) of LID/ΔM2-2/1030s (n = 21) or placebo (n = 11). The RSV serum antibodies, vaccine shedding, and reactogenicity were assessed. During the following RSV season, medically attended acute respiratory illness (MAARI) and pre- and postsurveillance serum antibody titers were monitored. RESULTS: Eighty-five percent of vaccinees shed LID/ΔM2-2/1030s vaccine (median peak nasal wash titers: 3.1 log10 PFU/mL by immunoplaque assay; 5.1 log10 copies/mL by reverse-transcription quantitative polymerase chain reaction) and had ≥4-fold rise in serum-neutralizing antibodies. Respiratory symptoms and fever were common (60% vaccinees and 27% placebo recipients). One vaccinee had grade 2 wheezing with rhinovirus but without concurrent LID/ΔM2-2/1030s shedding. Five of 19 vaccinees had ≥4-fold increases in antibody titers postsurveillance without RSV-MAARI, indicating anamnestic responses without significant illness after infection with community-acquired RSV. CONCLUSIONS: LID/ΔM2-2/1030s had excellent infectivity without evidence of genetic instability, induced durable immunity, and primed for anamnestic antibody responses, making it an attractive candidate for further evaluation.

An anthropometric survey of US pre-term and full-term neonates.

BACKGROUND: Anthropometric data prove valuable for screening and monitoring various medical conditions. In young infants, however, only weight, length and head circumference are represented in publicly accessible databases. AIM: To characterise length and circumferential measures in pre-term and full-term infants up to 90 days post-natal. SUBJECTS AND METHODS: In eight US medical centres, trained raters recorded humeral, ulnar, femoral, tibial and fibular lengths along with mid-upper arm, mid-thigh, chest, abdominal and neck circumference. Data were pooled by post-menstrual age into 1-week intervals and population curves created using the lambda, mu and sigma (LMS) method. Goodness-of-fit was assessed by examining de-trended quantile-quantile plots, Q statistics and fitted centiles overlaid on empirical centiles. RESULTS: In total, 2097 infants were enrolled in this study with a mean ± SD gestational age and post-natal age of 37.1 ± 3.3 weeks and 27.3 ± 25.3 days, respectively. A re-scale option was used to describe all curves. The resultant models reliably characterised anthropometric measures from 33-52 weeks PMA, with less certainty at the extremes (27-55 weeks). CONCLUSION: The population curves generated under this investigation expand existing reference data on a comprehensive set of anthropometric traits in infants through the first 90 days post-natal.

A Weight Estimation Strategy for Preterm and Full-Term Infants.

Weight is the foremost marker of health outcomes in infants; however, the majority of community workers and health care providers in remote, resource-constrained settings have limited access to functional scales. This study develops and validates a simple weight estimation strategy for infants that addresses the limitations of current approaches. Circumferential and segmental anthropometric measures were evaluated for their relationship to infant weight and length. Data derived from 2097 US infants (n = 1681 for model development, n = 416 for validation). Statistical and practical considerations informed final measurement selection. Head circumference and chest circumference demonstrated the best correlations with weight (r = 0.89) and length (r = 0.94 and 0.93), and were among the most reproducible as reflected by intraclass correlation coefficients (>0.98). The head circumference and chest circumference combination offered better goodness-of-fit and smaller limits of agreement than did either measure alone. The final model predicted weight within 10% and 15% of actual for 84% and 94% of infants, respectively, with no bias for postnatal age (P = .76), gestational age (P = .10), and sex (P = .25). The model requires simple summation to generate a weight estimate and can be embodied as a low-cost, paper-based device.