Live Respiratory Syncytial Virus (RSV) Vaccine Candidate Containing Stabilized Temperature-Sensitivity Mutations Is Highly Attenuated in RSV-Seronegative Infants and Children.

Background: Respiratory syncytial virus (RSV) is the most important viral cause of severe respiratory illness in young children and lacks a vaccine. RSV cold-passage/stabilized 2 (RSVcps2) is a modification of a previously evaluated vaccine candidate in which 2 major attenuating mutations have been stabilized against deattenuation.

Methods: RSV-seronegative 6-24-month-old children received an intranasal dose of 105.

B and T Cell Phenotypic Profiles of African HIV-Infected and HIV-Exposed Uninfected Infants: Associations with Antibody Responses to the Pentavalent Rotavirus Vaccine.

We examined associations between B and T cell phenotypic profiles and antibody responses to the pentavalent rotavirus vaccine (RV5) in perinatally HIV-infected (PHIV) infants on antiretroviral therapy and in HIV-exposed uninfected (PHEU) infants enrolled in International Maternal Pediatric Adolescent AIDS Clinical Trials P1072 study (NCT00880698). Of 17 B and T cell subsets analyzed, PHIV and PHEU differed only in the number of CD4+ T cells and frequency of naive B cells, which were higher in PHEU than in PHIV. In contrast, the B and T cell phenotypic profiles of PHIV and PHEU markedly differed from those of geographically matched contemporary HIV-unexposed infants.

Bone Age and Mineral Density Assessments Using Plain Roentgenograms in Tenofovir-exposed Infants in Malawi and Brazil Enrolled in HIV Prevention Trials Network 057.

Background: Tenofovir disoproxil fumarate (TDF) use during pregnancy has been increasing, and studies linking bone toxicity with exposure to TDF have raised concern for its use in infants.

Methods: Hand/wrist and spine radiographs were obtained at 3 days and 12 weeks of age in infants born to HIV-infected pregnant women enrolled in the HIV Prevention Trials Network 057 pharmacokinetic study of TDF conducted in Malawi and Brazil assigned to 3 TDF dosing cohorts. In cohort 1, mothers received 600 mg of TDF during labor.

Safety and immunogenicity of a live attenuated pentavalent rotavirus vaccine in HIV-exposed infants with or without HIV infection in Africa.

Objective: Although many HIV-infected (HIV+) and HIV-exposed but uninfected (HEU) infants have received live rotavirus vaccines since the WHO recommended universal administration of these vaccines to infants, there has been limited prospective information on their safety and immunogenicity in either group of infants.

Design/methods: We performed a randomized, double-blinded, placebo-controlled trial of the safety and immunogenicity of oral pentavalent rotavirus vaccine (RV5) administered to HIV+ and HEU infants in four African countries. Ninety-three percent of HIV+ infants were receiving antiretroviral therapy prior to vaccination.

Pharmacokinetics and safety of tenofovir in HIV-infected women during labor and their infants during the first week of life.

Background: Data describing the pharmacokinetics and safety of tenofovir in neonates are lacking.

Methods: The HIV Prevention Trials Network 057 protocol was a phase 1, open-label study of the pharmacokinetics and safety of tenofovir disoproxil fumarate (TDF) in HIV-infected women during labor and their infants during the first week of life with 4 dosing cohorts: maternal 600 mg doses/no infant dosing; no maternal dosing/infant 4 mg/kg doses on days 0, 3, and 5; maternal 900 mg doses/infant 6 mg/kg doses on days 0, 3, and 5; maternal 600 mg doses/infant 6 mg/kg daily for 7 doses. Pharmacokinetic sampling was performed on cohort 1 and 3 mothers and all infants.

A trimeric, V2-deleted HIV-1 envelope glycoprotein vaccine elicits potent neutralizing antibodies but limited breadth of neutralization in human volunteers.

Background: A key missing element in the development of a successful human immunodeficiency virus (HIV) vaccine is an immunogen that can generate broadly cross-neutralizing antibodies against primary isolates of the virus.

Methods: This phase 1 clinical trial employed a DNA prime and subunit envelope protein boost in an attempt to generate cellular and humoral immune responses that might be desirable in a protective HIV vaccine. Priming was performed via intramuscular injection with gag and env DNA adsorbed to polylactide coglycolide microspheres, followed by boosting with a recombinant trimeric envelope (Env) glycoprotein delivered in MF59 adjuvant.

Broadening inclusion of vulnerable populations in HIV vaccine trials.

The urgent need for a preventive HIV vaccine, as well as the complexities of its development, calls for timely and reinforced efforts to ensure vaccine licensure for use in a broad range of at-risk populations from the outset. Such an integrated strategy to HIV vaccine development should include infants of HIV-infected women, adolescents and injection drug users. A safe and effective HIV vaccine licensed for use in these populations, in addition to sexually active adults, would probably have the most timely and profound impact on the HIV/AIDS pandemic.

Pyridostigmine, diethyltoluamide, permethrin, and stress: a double-blind, randomized, placebo-controlled trial to assess safety.

Objective: To determine whether short-term human exposure to pyridostigmine bromide, diethyltoluamide, and permethrin, at rest or under stress, adversely affects short-term physical or neurocognitive performance.

Participants And Methods: A multicenter, prospective, double-blind, placebo-controlled crossover trial exposing 64 volunteers to permethrin-impregnated uniforms, diethyltoluamide-containing skin cream, oral pyridostigmine, and corresponding placebos was performed. Each participant had 4 separate sessions, ensuring exposure to all treatments and placebos under both stress and rest conditions in random order.

Military hospitalizations among deployed US service members following anthrax vaccination, 1998-2001.

Safety concerns have confronted the Department of Defense Anthrax Vaccine Immunization Program since inception in 1998. To determine if anthrax vaccination was associated with an increased risk of hospitalization, a historical cohort study utilizing pre- and post-anthrax-vaccination hospitalizations was undertaken and analyzed with Cox proportional hazards models. The study population consisted of 170,723 active duty US service members who were anthrax-vaccinated and deployed during the time period January 1, 1998 to December 31, 2001.

Self-reported reproductive outcomes among male and female 1991 Gulf War era US military veterans.

Background: Following the 1991 Gulf War, some veterans expressed concerns regarding their reproductive health. Our objective was to assess whether an association exists between deployment to the 1991 Gulf War and self-reported adverse pregnancy outcomes.

Methods: Using a modified Dillman technique with telephone follow-up, we conducted a survey via a postal questionnaire from February 1996-August 1997 to compare selected reproductive outcomes among 10,000 US veterans deployed to the 1991 Gulf War with those of 10,000 nondeployed Gulf War era veterans.

Monitoring anthrax vaccine safety in US military service members on active duty: surveillance of 1998 hospitalizations in temporal association with anthrax immunization.

We compared 1998 hospitalizations in active-duty US military personnel for possible temporal association with anthrax immunization. Immunization, demographic, and hospitalization data were analyzed using Cox proportional hazards modeling for hospitalization within 42 days of vaccination. Discharge diagnoses were aggregated into 14 International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) categories.