In this book, Eli Carter explores the ways in which the movement away from historically popular telenovelas toward new television and internet series is creating dramatic shifts in how Brazil ...imagines itself as a nation, especially within the context of an increasingly connected global mediascape.
Neutralizing and non-neutralizing antibodies to linear epitopes on HIV-1 envelope glycoproteins have potential to mediate antiviral effector functions that could be beneficial to vaccine-induced ...protection. Here, plasma IgG responses were assessed in three HIV-1 gp120 vaccine efficacy trials (RV144, Vax003, Vax004) and in HIV-1-infected individuals by using arrays of overlapping peptides spanning the entire consensus gp160 of all major genetic subtypes and circulating recombinant forms (CRFs) of the virus. In RV144, where 31.2% efficacy against HIV-1 infection was seen, dominant responses targeted the C1, V2, V3 and C5 regions of gp120. An analysis of RV144 case-control samples showed that IgG to V2 CRF01_AE significantly inversely correlated with infection risk (OR= 0.54, p=0.0042), as did the response to other V2 subtypes (OR=0.60-0.63, p=0.016-0.025). The response to V3 CRF01_AE also inversely correlated with infection risk but only in vaccine recipients who had lower levels of other antibodies, especially Env-specific plasma IgA (OR=0.49, p=0.007) and neutralizing antibodies (OR=0.5, p=0.008). Responses to C1 and C5 showed no significant correlation with infection risk. In Vax003 and Vax004, where no significant protection was seen, serum IgG responses targeted the same epitopes as in RV144 with the exception of an additional C1 reactivity in Vax003 and infrequent V2 reactivity in Vax004. In HIV-1 infected subjects, dominant responses targeted the V3 and C5 regions of gp120, as well as the immunodominant domain, heptad repeat 1 (HR-1) and membrane proximal external region (MPER) of gp41. These results highlight the presence of several dominant linear B cell epitopes on the HIV-1 envelope glycoproteins. They also generate the hypothesis that IgG to linear epitopes in the V2 and V3 regions of gp120 are part of a complex interplay of immune responses that contributed to protection in RV144.
Abstract We present new high-spectral-resolution observations ( R = λ /Δ λ = 7000) of the filamentary nebula surrounding NGC 1275, the central galaxy of the Perseus cluster. These observations have ...been obtained with SITELLE, an imaging Fourier transform spectrometer installed on the Canada–France–Hawai Telescope with a field of view of 11 ′ × 11 ′ , encapsulating the entire filamentary structure of ionized gas despite its large size of 80 kpc × 50 kpc. Here, we present renewed fluxes, velocities, and velocity dispersion maps that show in great detail the kinematics of the optical nebula at S ii λ 6716, S ii λ 6731, N ii λ 6584, H α (6563 Å), and N ii λ 6548. These maps reveal the existence of a bright flattened disk-shaped structure in the core extending to r ∼10 kpc and dominated by a chaotic velocity field. This structure is located in the wake of X-ray cavities and characterized by a high mean velocity dispersion of 134 km s −1 . The disk-shaped structure is surrounded by an extended array of filaments spread out to r ∼ 50 kpc that are 10 times fainter in flux, remarkably quiescent, and have a uniform mean velocity dispersion of 44 km s −1 . This stability is puzzling given that the cluster core exhibits several energetic phenomena. Based on these results, we argue that there are two mechanisms that form multiphase gas in clusters of galaxies: a first triggered in the wake of X-ray cavities leading to more turbulent multiphase gas and a second, distinct mechanism, that is gentle and leads to large-scale multiphase gas spreading throughout the core.
Non-neutralizing IgG to the V1V2 loop of HIV-1 gp120 correlates with a decreased risk of HIV-1 infection but the mechanism of protection remains unknown. This V1V2 IgG correlate was identified in ...RV144 Thai trial vaccine recipients, who were primed with a canarypox vector expressing membrane-bound gp120 (vCP1521) and boosted with vCP1521 plus a mixture gp120 proteins from clade B and clade CRF01_AE (B/E gp120). We sought to determine whether the mechanism of vaccine protection might involve antibody-dependent complement activation. Complement activation was measured as a function of complement component C3d deposition on V1V2-coated beads in the presence of RV144 sera. Variable levels of complement activation were detected two weeks post final boosting in RV144, which is when the V1V2 IgG correlate was identified. The magnitude of complement activation correlated with V1V2-specific serum IgG and was stronger and more common in RV144 than in HIV-1 infected individuals and two related HIV-1 vaccine trials, VAX003 and VAX004, where no protection was seen. After adjusting for gp120 IgA, V1V2 IgG, gender, and risk score, complement activation by case-control plasmas from RV144 correlated inversely with a reduced risk of HIV-1 infection, with odds ratio for positive versus negative response to TH023-V1V2 0.42 (95% CI 0.18 to 0.99, p = 0.048) and to A244-V1V2 0.49 (95% CI 0.21 to 1.10, p = 0.085). These results suggest that complement activity may have contributed in part to modest protection against the acquisition of HIV-1 infection seen in the RV144 trial.
The Brazilian television industry is one of the most productive and commercially successful in the world. At the forefront of this industry is TV Globo and its production of standardizedtelenovelas, ...which millions of Brazilians and viewers from over 130 countries watch nightly. Eli Lee Carter examines the field of television production by focusing on the work of one of Brazil's greatest living directors, Luiz Fernando Carvalho. Through an emphasis on Carvalho's thirty-plus year career working for TV Globo, his unique mode of production, and his development of a singular aesthetic as a reaction to the dominanttelenovelagenre, Carter sheds new light on Brazilian television's history, its current state, and where it is going-as new legislation and technology push it increasingly toward a post-network era.
Eliciting durable humoral immunity with sufficient breadth and magnitude is important for HIV-1 vaccine design. The HVTN 114 vaccine trial evaluated different boost regimens administered after a ...7-year rest period in participants previously enrolled in HVTN 205, who received either three MVA/HIV62B (MMM) or two DNA and two MVA/HIV62B (DDMM) injections; both vaccines expressed multiple HIV-1 antigens in non-infectious virus-like-particles. The primary objective of HVTN 114 was to assess the impact of a heterologous gp120 protein AIDSVAX B/E boost on the magnitude, breadth and durability of vaccine-induced immune responses.
We enrolled 27 participants from HVTN 205 into five groups. Eight participants who previously received MMM were randomized and boosted with either MVA/HIV62B alone (T1; n = 4) or MVA/HIV62B and AIDSVAX B/E (T2; n = 4). Nineteen participants who received DDMM were randomized and boosted with MVA/HIV62B alone (T3; n = 6), MVA/HIV62B and AIDSVAX B/E (T4; n = 6), or AIDSVAX B/E alone (T5; n = 7). Boosts were at months 0 and 4. Participants were followed for safety and immunogenicity for 10 months and were pooled for analysis based on the regimen: MVA-only (T1 + T3), MVA + AIDSVAX (T2 + T4), and AIDSVAX-only (T5).
All regimens were safe and well-tolerated. Prior to the boost vaccination, binding antibody and CD4+T-cell responses were observed 7 years after HVTN 205 vaccinations. Late boosting with AIDSVAX, with or without MVA, resulted in high binding antibody responses to gp120 and V1V2 epitopes, with increased magnitude and breadth compared to those observed in HVTN 205. Late boosting with MVA, with or without AIDSVAX, resulted in increased gp140 and gp41 antibody responses and higher CD4+T-cell responses to Env and Gag.
Late boosting with AIDSVAX, alone or in combination with MVA, can broaden binding antibody responses and increase T-cell responses even years following the original MVA/HIV62B with or without DNA-priming vaccine.
During the COVID-19 pandemic, many countries have issued stay-at-home orders (SAHOs) to reduce viral transmission. Because of their social and economic consequences, SAHOs are a politically risky ...decision for governments. Researchers typically attribute public health policymaking to five theoretically significant factors: political, scientific, social, economic, and external. However, a narrow focus on extant theory runs the risk of biasing findings and missing novel insights. This research employs machine learning to shift the focus from theory to data to generate hypotheses and insights “born from the data” and unconstrained by current knowledge. Beneficially, this approach can also confirm the extant theory. We apply machine learning in the form of a random forest classifier to a novel and multiple-domain data set of 88 variables to identify the most significant predictors of the issuance of a COVID-19-related SAHO in African countries (n = 54). Our data set includes a wide range of variables from sources such as the World Health Organization that cover the five principal theoretical factors and previously ignored domains. Generated using 1000 simulations, our model identifies a combination of theoretically significant and novel variables as the most important to the issuance of a SAHO and has a predictive accuracy using 10 variables of 78%, which represents a 56% increase in accuracy compared to simply predicting the modal outcome.
In the HIV-1 vaccine trial RV144, ALVAC-HIV prime with an AIDSVAX® B/E boost reduced HIV-1 acquisition by 31% at 42 months post first vaccination. The bivalent AIDSVAX® B/E vaccine contains two gp120 ...envelope glycoproteins, one from the subtype B HIV-1 MN isolate and one from the subtype CRF01_AE A244 isolate. Each envelope glycoprotein harbors a highly conserved 27-amino acid HSV-1 glycoprotein D (gD) tag sequence that shares 93% sequence identity with the HSV-2 gD sequence. We assessed whether vaccine-induced anti-gD antibodies protected females against HSV-2 acquisition in RV144.
Of the women enrolled in RV144, 777 vaccine and 807 placebo recipients were eligible and randomly selected according to their pre-vaccination HSV-1 and HSV-2 serostatus for analysis. Immunoglobulin G (IgG) and IgA responses to gD were determined by a binding antibody multiplex assay and HSV-2 serostatus was determined by Western blot analysis. Ninety-three percent and 75% of the vaccine recipients had anti-gD IgG and IgA responses two weeks post last vaccination, respectively. There was no evidence of reduction in HSV-2 infection by vaccination compared to placebo recipients over 78 weeks of follow-up. The annual incidence of HSV-2 infection in individuals who were HSV-2 negative at baseline or HSV-1 positive and HSV-2 indeterminate at baseline were 4.38/100 person-years (py) and 3.28/100 py in the vaccine and placebo groups, respectively. Baseline HSV-1 status did not affect subsequent HSV-2 acquisition. Specifically, the estimated odds ratio of HSV-2 infection by Week 78 for female placebo recipients who were baseline HSV-1 positive (n = 422) vs. negative (n = 1120) was 1.14 95% confidence interval 0.66 to 1.94, p = 0.64). No evidence of reduction in the incidence of HSV-2 infection by vaccination was detected.
AIDSVAX® B/E containing gD did not confer protection from HSV-2 acquisition in HSV-2 seronegative women, despite eliciting anti-gD serum antibodies.