Immunogenicity and Safety of 3 Formulations of a Respiratory Syncytial Virus Candidate Vaccine in Nonpregnant Women: A Phase 2, Randomized Trial.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of respiratory tract illness and hospitalization in neonates and infants. RSV vaccination during pregnancy may protect offspring in their first months of life. METHODS: This randomized, observer-blind, multicenter, phase 2 study evaluated the immunogenicity and safety of an RSV candidate vaccine in healthy nonpregnant women aged 18-45 years. Four hundred participants were randomized (1:1:1:1) to receive a single intramuscular dose of vaccine containing 30 µg, 60 µg, or 120 µg of RSV fusion protein engineered to preferentially maintain a prefusion conformation (RSV-PreF vaccine) or placebo. RESULTS: Thirty days postvaccination, RSV-A neutralizing antibody geometric mean titers (GMTs) increased 3.75-, 4.42- and 4.36-fold; RSV-B neutralizing antibody GMTs 2.36-, 2.54- and 2.76-fold; and palivizumab competing antibody (PCA) concentrations 11.69-, 14.38- and 14.24-fold compared with baseline levels in the 30 µg, 60 µg, and 120 µg RSV-PreF groups, respectively. Antibody titers and PCA concentrations at day 30 were significantly higher with the 120 µg compared to the 30 µg RSV-PreF vaccine. All RSV-PreF vaccine formulations and the placebo had similar reactogenicity profiles. No serious adverse events were considered to be related to the RSV-PreF vaccine. CONCLUSIONS: The 3 formulations of the investigational RSV-PreF vaccine were well-tolerated and induced RSV-A and RSV-B neutralizing antibodies and PCAs in healthy, nonpregnant women. CLINICAL TRIALS REGISTRATION: NCT02956837.

Gene-environment interactions with CD14 C-260T and their relationship to total serum IgE levels in adults.

BACKGROUND: Both endotoxin exposure and a single nucleotide polymorphism in one of its receptors, CD14 C-260T, have been separately associated with total serum IgE levels. Furred pets might also influence IgE levels through their effects on endotoxin levels. However, how these factors interact to influence total IgE levels is not well known, especially in adults. OBJECTIVE: We sought to investigate the interactive relationship between endotoxin levels, pet exposure, and CD14 C-260T genotype on total serum IgE levels in adults. METHODS: Mothers enrolled in an ongoing cohort study were genotyped for the CD14 C-260T polymorphism. Exposure to pets was assessed by using questionnaires and dust allergen levels collected in the home. Endotoxin exposure was estimated by using dust collected from mothers' bedroom floors. The primary outcome measure was total serum IgE level. RESULTS: CD14 C-260T genotype was assessed in 517 (85.2%) of the 607 women enrolled in the study. The CD14 C-260T genotype was significantly associated with total IgE levels; however, this relationship appeared to be modified by the level of endotoxin exposure. Similar interactions between CD14 C-260T and pet exposure were not seen, regardless of the measure of pet exposure used. CONCLUSIONS: The CD14 C-260T genotype and endotoxin exposure together appear to influence total serum IgE levels in adults. The absence of a similar gene-environment interaction for pet exposure suggests separate mechanisms of action. CLINICAL IMPLICATIONS: A common polymorphism in the endotoxin receptor, CD14 C-260T, and dust endotoxin levels in the home might interact to influence total serum IgE levels into adulthood.