7 research outputs found
Immunogenicity of the RTS,S/AS01 malaria vaccine and implications for duration of vaccine efficacy:Secondary analysis of data from a phase 3 randomised controlled trial
BACKGROUND: The RTS,S/AS01 malaria vaccine targets the circumsporozoite protein, inducing antibodies associated with the prevention of Plasmodium falciparum infection. We assessed the association between anti-circumsporozoite antibody titres and the magnitude and duration of vaccine efficacy using data from a phase 3 trial done between 2009 and 2014. METHODS: Using data from 8922 African children aged 5-17 months and 6537 African infants aged 6-12 weeks at first vaccination, we analysed the determinants of immunogenicity after RTS,S/AS01 vaccination with or without a booster dose. We assessed the association between the incidence of clinical malaria and anti-circumsporozoite antibody titres using a model of anti-circumsporozoite antibody dynamics and the natural acquisition of protective immunity over time. FINDINGS: RTS,S/AS01-induced anti-circumsporozoite antibody titres were greater in children aged 5-17 months than in those aged 6-12 weeks. Pre-vaccination anti-circumsporozoite titres were associated with lower immunogenicity in children aged 6-12 weeks and higher immunogenicity in those aged 5-17 months. The immunogenicity of the booster dose was strongly associated with immunogenicity after primary vaccination. Anti-circumsporozoite titres wane according to a biphasic exponential distribution. In participants aged 5-17 months, the half-life of the short-lived component of the antibody response was 45 days (95% credible interval 42-48) and that of the long-lived component was 591 days (557-632). After primary vaccination 12% (11-13) of the response was estimated to be long-lived, rising to 30% (28-32%) after a booster dose. An anti-circumsporozoite antibody titre of 121 EU/mL (98-153) was estimated to prevent 50% of infections. Waning anti-circumsporozoite antibody titres predict the duration of efficacy against clinical malaria across different age categories and transmission intensities, and efficacy wanes more rapidly at higher transmission intensity. INTERPRETATION: Anti-circumsporozoite antibody titres are a surrogate of protection for the magnitude and duration of RTS,S/AS01 efficacy, with or without a booster dose, providing a valuable surrogate of effectiveness for new RTS,S formulations in the age groups considered. FUNDING: UK Medical Research Council
Immunogenicity of the RTS,S/AS01 Malaria Vaccine and\ud Implications for Duration of Vaccine Efficacy: Secondary\ud Analysis of Data from a Phase 3 Randomised Controlled Trial
The RTS,S/AS01 malaria vaccine targets the circumsporozoite protein, inducing antibodies associated with the prevention of Plasmodium falciparum infection. We assessed the association between anti-circumsporozoite antibody titres and the magnitude and duration of vaccine effi cacy using data from a phase 3 trial done between 2009 and 2014. Using data from 8922 African children aged 5 1317 months and 6537 African infants aged 6 1312 weeks at first vaccination, we analysed the determinants of immunogenicity after RTS,S/AS01 vaccination with or without a booster dose. We assessed the association between the incidence of clinical malaria and anti-circumsporozoite antibody titres using a model of anti-circumsporozoite antibody dynamics and the natural acquisition of protective immunity over time. RTS,S/AS01-induced anti-circumsporozoite antibody titres were greater in children aged 5 1317 months than in those aged 6 1312 weeks. Pre-vaccination anti-circumsporozoite titres were associated with lower immunogenicity in children aged 6 1312 weeks and higher immunogenicity in those aged 5 1317 months. The immunogenicity of the booster dose was strongly associated with immunogenicity after primary vaccination. Anti-circumsporozoite titres wane according to a biphasic exponential distribution. In participants aged 5 1317 months, the half-life of the shortlived component of the antibody response was 45 days (95% credible interval 42 1348) and that of the long-lived component was 591 days (557 13632). After primary vaccination 12% (11 1313) of the response was estimated to be longlived, rising to 30% (28 1332%) after a booster dose. An anti-circumsporozoite antibody titre of 121 EU/mL (98 13153) was estimated to prevent 50% of infections. Waning anti-circumsporozoite antibody titres predict the duration of effi cacy against clinical malaria across diff erent age categories and transmission intensities, and effi cacy wanes more rapidly at higher transmission intensity Anti-circumsporozoite antibody titres are a surrogate of protection for the magnitude and duration of RTS,S/AS01 effi cacy, with or without a booster dose, providing a valuable surrogate of eff ectiveness for new RTS,S formulations in the age groups considered
Cutaneous Responses to Endothelin-1 and Histamine in Patients with Vibration White Finger
Focused ion beam deposited carbon-platinum nanowires for cryogenic resistive thermometry
Immunogenicity of the RTS,S/AS01 malaria vaccine and implications for duration of vaccine efficacy: secondary analysis of data from a phase 3 randomised controlled trial
BACKGROUND: The RTS,S/AS01 malaria vaccine targets the
circumsporozoite protein, inducing antibodies associated with
the prevention of Plasmodium falciparum infection. We assessed
the association between anti-circumsporozoite antibody titres
and the magnitude and duration of vaccine efficacy using data
from a phase 3 trial done between 2009 and 2014. METHODS: Using
data from 8922 African children aged 5-17 months and 6537
African infants aged 6-12 weeks at first vaccination, we
analysed the determinants of immunogenicity after RTS,S/AS01
vaccination with or without a booster dose. We assessed the
association between the incidence of clinical malaria and
anti-circumsporozoite antibody titres using a model of
anti-circumsporozoite antibody dynamics and the natural
acquisition of protective immunity over time. FINDINGS:
RTS,S/AS01-induced anti-circumsporozoite antibody titres were
greater in children aged 5-17 months than in those aged 6-12
weeks. Pre-vaccination anti-circumsporozoite titres were
associated with lower immunogenicity in children aged 6-12 weeks
and higher immunogenicity in those aged 5-17 months. The
immunogenicity of the booster dose was strongly associated with
immunogenicity after primary vaccination. Anti-circumsporozoite
titres wane according to a biphasic exponential distribution. In
participants aged 5-17 months, the half-life of the short-lived
component of the antibody response was 45 days (95% credible
interval 42-48) and that of the long-lived component was 591
days (557-632). After primary vaccination 12% (11-13) of the
response was estimated to be long-lived, rising to 30% (28-32%)
after a booster dose. An anti-circumsporozoite antibody titre of
121 EU/mL (98-153) was estimated to prevent 50% of infections.
Waning anti-circumsporozoite antibody titres predict the
duration of efficacy against clinical malaria across different
age categories and transmission intensities, and efficacy wanes
more rapidly at higher transmission intensity. INTERPRETATION:
Anti-circumsporozoite antibody titres are a surrogate of
protection for the magnitude and duration of RTS,S/AS01
efficacy, with or without a booster dose, providing a valuable
surrogate of effectiveness for new RTS,S formulations in the age
groups considered. FUNDING: UK Medical Research Council
Results of the Prospective Evaluation of Radial Keratotomy (PERK) Study One Year After Surgery
The Prospective Evaluation of Radial Keratotomy (PERK) study is a nine-center, self-controlled clinical trial of a standardized technique of radial keratotomy in 435 patients who had physiologic myopia with a preoperative refraction between −2.00 and −8.00 diopters. The surgical technique consisted of eight incisions using a diamond micrometer knife with blade length determined by intraoperative ultrasonic pachymetry and the diameter of central clear zone determined by preoperative refraction. At one year after surgery, myopia was reduced in all eyes; 60% were within ±1.00 diopter of emmetropia; 30% were undercorrected and 10% were overcorrected by more than 1.00 diopter (range of refraction, −4.25 to +3.38 D). Uncorrected visual acuity was 20/40 or better in 78% of eyes. The operation was most effective in eyes with a refraction between −2.00 and −4.25 diopters.
Thirteen percent of patients lost one or two Snellen lines of best corrected visual acuity. However, all but three eyes could be corrected to 20/20. Ten percent of patients increased astigmatism more than 1.00 diopter. Disabling glare was not detected with a clinical glare tester, but three patients reduced their driving at night because of glare. Between six months and one year, the refraction changed by >0.50 diopters in 19% of eyes
\u3ci\u3eDrosophila\u3c/i\u3e Muller F Elements Maintain a Distinct Set of Genomic Properties Over 40 Million Years of Evolution
The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25–50%) than euchromatic reference regions (3–11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11–27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4–3.6 vs. 8.4–8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu