Safety and Immunogenicity of an AMA-1 Malaria Vaccine in Malian Adults: Results of a Phase 1 Randomized Controlled Trial

The objective was to evaluate the safety, reactogenicity and immunogenicity of the AMA-1-based blood-stage malaria vaccine FMP2.1/AS02A in adults exposed to seasonal malaria.A phase 1 double blind randomized controlled dose escalation trial was conducted in Bandiagara, Mali, West Africa, a rural town with intense seasonal transmission of Plasmodium falciparum malaria. The malaria vaccine FMP2.1/AS02A is a recombinant protein (FMP2.1) based on apical membrane antigen-1 (AMA-1) from the 3D7 clone of P. falciparum, adjuvanted with AS02A. The comparator vaccine was a cell-culture rabies virus vaccine (RabAvert). Sixty healthy, malaria-experienced adults aged 18-55 y were recruited into 2 cohorts and randomized to receive either a half dose or full dose of the malaria vaccine (FMP2.1 25 microg/AS02A 0.25 mL or FMP2.1 50 microg/AS02A 0.5 mL) or rabies vaccine given in 3 doses at 0, 1 and 2 mo, and were followed for 1 y. Solicited symptoms were assessed for 7 d and unsolicited symptoms for 30 d after each vaccination. Serious adverse events were assessed throughout the study. Titers of anti-AMA-1 antibodies were measured by ELISA and P. falciparum growth inhibition assays were performed on sera collected at pre- and post-vaccination time points. Transient local pain and swelling were common and more frequent in both malaria vaccine dosage groups than in the comparator group. Anti-AMA-1 antibodies increased significantly in both malaria vaccine groups, peaking at nearly 5-fold and more than 6-fold higher than baseline in the half-dose and full-dose groups, respectively.The FMP2.1/AS02A vaccine had a good safety profile, was well-tolerated, and was highly immunogenic in malaria-exposed adults. This malaria vaccine is being evaluated in Phase 1 and 2 trials in children at this site

Completed SDSS-IV extended Baryon Oscillation Spectroscopic Survey: Cosmological implications from two decades of spectroscopic surveys at the Apache Point Observatory

We present the cosmological implications from final measurements of clustering using galaxies, quasars, and Ly α forests from the completed Sloan Digital Sky Survey (SDSS) lineage of experiments in large-scale structure. These experiments, composed of data from SDSS, SDSS-II, BOSS, and eBOSS, offer independent measurements of baryon acoustic oscillation (BAO) measurements of angular-diameter distances and Hubble distances relative to the sound horizon, r_{d}, from eight different samples and six measurements of the growth rate parameter, fσ_{8}, from redshift-space distortions (RSD). This composite sample is the most constraining of its kind and allows us to perform a comprehensive assessment of the cosmological model after two decades of dedicated spectroscopic observation. We show that the BAO data alone are able to rule out dark-energy-free models at more than eight standard deviations in an extension to the flat, Λ CDM model that allows for curvature. When combined with Planck Cosmic Microwave Background (CMB) measurements of temperature and polarization, under the same model, the BAO data provide nearly an order of magnitude improvement on curvature constraints relative to primary CMB constraints alone. Independent of distance measurements, the SDSS RSD data complement weak lensing measurements from the Dark Energy Survey (DES) in demonstrating a preference for a flat Λ CDM cosmological model when combined with Planck measurements. The combined BAO and RSD measurements indicate σ_{8} = 0.85 ± 0.03, implying a growth rate that is consistent with predictions from Planck temperature and polarization data and with General Relativity. When combining the results of SDSS BAO and RSD, Planck, Pantheon Type Ia supernovae (SNe Ia), and DES weak lensing and clustering measurements, all multiple-parameter extensions remain consistent with a Λ CDM model. Regardless of cosmological model, the precision on each of the three parameters, Ω_{Λ}, H_{0}, and σ_{8}, remains at roughly 1%, showing changes of less than 0.6% in the central values between models. In a model that allows for free curvature and a time-evolving equation of state for dark energy, the combined samples produce a constraint Ω_{k} = −0.0022 ± 0.0022. The dark energy constraints lead to w_{0} = −0.909 ± 0.081 and w_{a} = −0.49^{+0.35}_{-0.30}, corresponding to an equation of state of w_{p} = 1.018 ± 0.032 at a pivot redshift z_{p} = 0.29 and a Dark Energy Task Force Figure of Merit of 94. The inverse distance ladder measurement under this model yields H_{0} = 68.18 ± 0.79 km s^{-1} Mpc^{-1}, remaining in tension with several direct determination methods; the BAO data allow Hubble constant estimates that are robust against the assumption of the cosmological model. In addition, the BAO data allow estimates of H_{0} that are independent of the CMB data, with similar central values and precision under a Λ CDM model. Our most constraining combination of data gives the upper limit on the sum of neutrino masses at ∑m_{v} < 0.115 eV (95% confidence). Finally, we consider the improvements in cosmology constraints over the last decade by comparing our results to a sample representative of the period 2000–2010. We compute the relative gain across the five dimensions spanned by w, Ω_{k}, ∑m_{v}, H_{0}, H_{0}, and σ_{8} and find that the SDSS BAO and RSD data reduce the total posterior volume by a factor of 40 relative to the previous generation. Adding again the Planck, DES, and Pantheon SN Ia samples leads to an overall contraction in the five-dimensional posterior volume of 3 orders of magnitude

Antibody isotype analysis of malaria-nematode co-infection: problems and solutions associated with cross-reactivity

<p>Abstract</p> <p>Background</p> <p>Antibody isotype responses can be useful as indicators of immune bias during infection. In studies of parasite co-infection however, interpretation of immune bias is complicated by the occurrence of cross-reactive antibodies. To confidently attribute shifts in immune bias to the presence of a co-infecting parasite, we suggest practical approaches to account for antibody cross-reactivity. The potential for cross-reactive antibodies to influence disease outcome is also discussed.</p> <p>Results</p> <p>Utilising two murine models of malaria-helminth co-infection we analysed antibody responses of mice singly- or co-infected with <it>Plasmodium chabaudi chabaudi </it>and <it>Nippostrongylus brasiliensis </it>or <it>Litomosoides sigmodontis</it>. We observed cross-reactive antibody responses that recognised antigens from both pathogens irrespective of whether crude parasite antigen preparations or purified recombinant proteins were used in ELISA. These responses were not apparent in control mice. The relative strength of cross-reactive versus antigen-specific responses was determined by calculating antibody titre. In addition, we analysed antibody binding to periodate-treated antigens, to distinguish responses targeted to protein versus carbohydrate moieties. Periodate treatment affected both antigen-specific and cross-reactive responses. For example, malaria-induced cross-reactive IgG1 responses were found to target the carbohydrate component of the helminth antigen, as they were not detected following periodate treatment. Interestingly, periodate treatment of recombinant malaria antigen Merozoite Surface Protein-1₁₉(MSP-1₁₉) resulted in increased detection of antigen-specific IgG2a responses in malaria-infected mice. This suggests that glycosylation may have been masking protein epitopes and that periodate-treated MSP-1₁₉may more closely reflect the natural non-glycosylated antigen seen during infection.</p> <p>Conclusions</p> <p>In order to utilize antibody isotypes as a measure of immune bias during co-infection studies, it is important to dissect antigen-specific from cross-reactive antibody responses. Calculating antibody titre, rather than using a single dilution of serum, as a measure of the relative strength of the response, largely accomplished this. Elimination of the carbohydrate moiety of an antigen that can often be the target of cross-reactive antibodies also proved useful.</p

The Completed SDSS-IV Extended Baryon Oscillation Spectroscopic Survey: Baryon Acoustic Oscillations with Ly alpha Forests

We present a measurement of baryonic acoustic oscillations (BAOs) from Lyα absorption and quasars at an effective redshift $z=2.33$ using the complete extended Baryonic Oscillation Spectroscopic Survey (eBOSS). The 16th and final eBOSS data release (SDSS DR16) contains all data from eBOSS and its predecessor, the Baryonic Oscillation Spectroscopic Survey (BOSS), providing 210,005 quasars with z q > 2.10 that are used to measure Lyα absorption. We measure the BAO scale both in the autocorrelation of Lyα absorption and in its cross-correlation with 341,468 quasars with redshift z q > 1.77. Apart from the statistical gain from new quasars and deeper observations, the main improvements over previous work come from more accurate modeling of physical and instrumental correlations and the use of new sets of mock data. Combining the BAO measurement from the auto- and cross-correlation yields the constraints of the two ratios ${D}_{H}(z\,=2.33)/{r}_{d}=8.99\pm 0.19$ and ${D}_{M}(z=2.33)/{r}_{d}=37.5\pm 1.1$, where the error bars are statistical. These results are within 1.5σ of the prediction of the flat-ΛCDM cosmology of Planck (2016). The analysis code, picca, the catalog of the flux transmission field measurements, and the Δχ 2 surfaces are publicly available

Completed SDSS-IV extended Baryon Oscillation Spectroscopic Survey: Cosmological implications from two decades of spectroscopic surveys at the Apache Point Observatory

We present the cosmological implications from final measurements of clustering using galaxies, quasars, and Lyα forests from the completed Sloan Digital Sky Survey (SDSS) lineage of experiments in large-scale structure. These experiments, composed of data from SDSS, SDSS-II, BOSS, and eBOSS, offer independent measurements of baryon acoustic oscillation (BAO) measurements of angular-diameter distances and Hubble distances relative to the sound horizon, rd, from eight different samples and six measurements of the growth rate parameter, fσ8, from redshift-space distortions (RSD). This composite sample is the most constraining of its kind and allows us to perform a comprehensive assessment of the cosmological model after two decades of dedicated spectroscopic observation. We show that the BAO data alone are able to rule out dark-energy-free models at more than eight standard deviations in an extension to the flat, ΛCDM model that allows for curvature. When combined with Planck Cosmic Microwave Background (CMB) measurements of temperature and polarization, under the same model, the BAO data provide nearly an order of magnitude improvement on curvature constraints relative to primary CMB constraints alone. Independent of distance measurements, the SDSS RSD data complement weak lensing measurements from the Dark Energy Survey (DES) in demonstrating a preference for a flat ΛCDM cosmological model when combined with Planck measurements. The combined BAO and RSD measurements indicate σ8=0.85±0.03, implying a growth rate that is consistent with predictions from Planck temperature and polarization data and with General Relativity. When combining the results of SDSS BAO and RSD, Planck, Pantheon Type Ia supernovae (SNe Ia), and DES weak lensing and clustering measurements, all multiple-parameter extensions remain consistent with a ΛCDM model. Regardless of cosmological model, the precision on each of the three parameters, ωΛ, H0, and σ8, remains at roughly 1%, showing changes of less than 0.6% in the central values between models. In a model that allows for free curvature and a time-evolving equation of state for dark energy, the combined samples produce a constraint ωk=-0.0022±0.0022. The dark energy constraints lead to w0=-0.909±0.081 and wa=-0.49-0.30+0.35, corresponding to an equation of state of wp=-1.018±0.032 at a pivot redshift zp=0.29 and a Dark Energy Task Force Figure of Merit of 94. The inverse distance ladder measurement under this model yields H0=68.18±0.79 km s-1 Mpc-1, remaining in tension with several direct determination methods; the BAO data allow Hubble constant estimates that are robust against the assumption of the cosmological model. In addition, the BAO data allow estimates of H0 that are independent of the CMB data, with similar central values and precision under a ΛCDM model. Our most constraining combination of data gives the upper limit on the sum of neutrino masses at mν&lt;0.115 eV (95% confidence). Finally, we consider the improvements in cosmology constraints over the last decade by comparing our results to a sample representative of the period 2000-2010. We compute the relative gain across the five dimensions spanned by w, ωk, mν, H0, and σ8 and find that the SDSS BAO and RSD data reduce the total posterior volume by a factor of 40 relative to the previous generation. Adding again the Planck, DES, and Pantheon SN Ia samples leads to an overall contraction in the five-dimensional posterior volume of 3 orders of magnitude