Safety, Tolerability, and Pharmacokinetics of the Broadly Neutralizing Human Immunodeficiency Virus (HIV)-1 Monoclonal Antibody VRC01 in HIV-Exposed Newborn Infants.

BACKGROUND: Although mother-to-child human immunodeficiency virus (HIV) transmission has dramatically decreased with maternal antiretroviral therapy, breast milk transmission accounts for most of the 180 000 new infant HIV infections annually. Broadly neutralizing antibodies (bNAb) may further reduce transmission. METHODS: A Phase 1 safety and pharmacokinetic study was conducted: a single subcutaneous (SC) dose of 20 or 40 mg/kg (Dose Groups 1 and 2, respectively) of the bNAb VRC01 was administered to HIV-exposed infants soon after birth. Breastfeeding infants (Dose Group 3) received 40 mg/kg SC VRC01 after birth and then 20 mg/kg/dose SC monthly. All infants received appropriate antiretroviral prophylaxis. RESULTS: Forty infants were enrolled (21 in the United States, 19 in Africa). Subcutaneous VRC01 was safe and well tolerated with only mild-to-moderate local reactions, primarily erythema, which rapidly resolved. For multiple-dose infants, local reactions decreased with subsequent injections. VRC01 was rapidly absorbed after administration, with peak concentrations 1-6 days postdose. The 40 mg/kg dose resulted in 13 of 14 infants achieving the serum 50 micrograms (mcg)/mL target at day 28. Dose Group 3 infants maintained concentrations greater than 50 mcg/mL throughout breastfeeding. CONCLUSIONS: Subcutaneous VRC01 as single or multiple doses is safe and well tolerated in very young infants and is suitable for further study to prevent HIV transmission in infants.

Live-Attenuated Respiratory Syncytial Virus Vaccine Candidate With Deletion of RNA Synthesis Regulatory Protein M2-2 is Highly Immunogenic in Children.

Background: Live respiratory syncytial virus (RSV) candidate vaccine LIDΔM2-2 is attenuated by deletion of the RSV RNA regulatory protein M2-2, resulting in upregulated viral gene transcription and antigen expression but reduced RNA replication. Methods: RSV-seronegative children ages 6-24 months received a single intranasal dose of 105 plaque forming units (PFU) of LIDΔM2-2 (n = 20) or placebo (n = 9) (NCT02237209, NCT02040831). RSV serum antibodies, vaccine infectivity, and reactogenicity were assessed. During the following RSV season, participants were monitored for respiratory illness and pre- and post-RSV season serum antibodies. Results: Vaccine virus was shed by 95% of vaccinees (median peak titers of 3.8 log10 PFU/mL by quantitative culture and 6.3 log10 copies/mL by PCR); 90% had ≥4-fold rise in serum neutralizing antibodies. Respiratory symptoms and fever were common in vaccine (95%) and placebo (78%). One vaccinee had grade 2 rhonchi concurrent with vaccine shedding, rhinovirus, and enterovirus. Eight of 19 vaccinees versus 2 of 9 placebo recipients had substantially increased RSV antibody titers after the RSV season without medically attended RSV disease, indicating anamnestic vaccine responses to wild-type RSV without significant illness. Conclusion: LIDΔM2-2 had excellent infectivity and immunogenicity, encouraging further study of vaccine candidates attenuated by M2-2 deletion. Clinical Trials Registration: NCT02237209, NCT02040831.

The Short- to Medium-Term Predictive Validity of Static and Dynamic Risk-of-Violence Measures in Medium- to Low-Secure Forensic and Civil Inpatients.

The prediction and subsequent management of aggression by psychiatric inpatients is a crucial role of the mental health professional. This retrospective cohort study examines the predictive validity of 10 static and dynamic risk-of-violence measures and subscales in 37 forensic and 37 civil inpatients residing in a medium- to-low security psychiatric facility for a period of up to 6 months. Retrospective file records were sourced to conduct an AUC analysis of the ROC curve for short- and medium-term follow-up periods. The hypothesis that dynamic measures would be better predictors than static measures over the short term was supported. Albeit to a lesser extent, dynamic measures were still better predictors than static measures over the medium term. This result was seen in both civil and forensic groups. Three previously untested measures were found to predict aggression within the sample. It is recommended that mental health services employ the use of dynamic measures when making short-term risk-of-violence predictions for civil and/or forensic inpatients.

Extensive phenotypic variation among allelic T-DNA inserts in Arabidopsis thaliana.

T-DNA insertion mutants are a tool used widely in Arabidopsis thaliana to disrupt gene function. We phenotyped multiple homozygous T-DNA A. thaliana mutants at each of two loci (AT1G11060 and AT4G00210). We measured life history traits, including germination, size at reproduction and fruit production. Allelic T-DNA lines differed for most traits at AT1G11060 but not at AT4G00210. However, insertions in exons differed from other insertion positions in AT4G00210 but not in AT1G11060. We found evidence for additional insertions in approximately half of the lines, but found few phenotypic consequences. In general, our results suggest that a cautious interpretation of T-DNA phenotypes is warranted.