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Vaccine protection against COVID-19 wanes over time and has been impacted by the emergence of new variants with increasing escape of neutralization. The COVID-19 Variant Immunologic Landscape (COVAIL) randomized clinical trial (clinicaltrials.gov NCT 05289037) compares the breadth, magnitude and durability of antibody responses induced by a second COVID-19 vaccine boost with mRNA (Moderna mRNA-1273 and Pfizer-BioNTech BNT162b2), or adjuvanted recombinant protein (Sanofi CoV2 preS DTM-AS03) monovalent or bivalent vaccine candidates targeting ancestral and variant SARS-CoV-2 spike antigens (Beta, Delta and Omicron BA.1). We found that boosting with a variant strain is not associated with loss in neutralization against the ancestral strain. However, while variant vaccines compared to the prototype/wildtype vaccines demonstrated higher neutralizing activity against Omicron BA.1 and BA.4/5 subvariants for up to 3 months after vaccination, neutralizing activity was lower for more recent Omicron subvariants. Our study, incorporating both antigenic distances and serologic landscapes, can provide a framework for objectively guiding decisions for future vaccine updates.

Se presenta un modelo cero dimensional para estimar la masa ablacionada y el impulso en propulsores de plasma pulsantes ablativos de Teflón® (PPPA), el cual es una modificación de modelos desarrollados con anterioridad. El modelo plantea el balance global de la energía, el cual considera la generación y transporte del pulso de corriente, la formación del arco, la disipación de energía por efecto Joule, la aceleración del plasma y la aceleración de los gases neutros. La ecuación resultante del balance de energía queda expresada en función de la masa ablacionada de Teflón® y de los principales parámetros eléctricos y geométricos del propulsor. Una expresión explícita de la masa que se ablaciona se obtiene desde este balance. También, se lleva a cabo un estudio de sensibilidad del nuevo modelo respecto de variables tales como la resistividad y la emisividad del plasma en el arco. Se comparan los resultados numéricos con aquellos dados en la literatura especializada para distintos PPPA. Finalmente, se identifican las variables más relevantes respecto a la predicción de la masa ablacionada, el bit de impulso y el impulso específico. To estimate the ablated mass and the impulse in Teflon® ablative pulsating plasma thrusters (PPPA), a zero-dimensional model is presented. This model introduces improvements to the models developed in the past. The new model uses the global energy balance, which considers the generation and transport of the current pulse, the arc formation, the energy dissipation by Joule effect, the acceleration of plasma and neutral gases. This energy equation is expressed as a function of the Teflon® ablated mass and the most important electric and geometric parameters of the thruster. From the energy balance, an explicit equation for the ablated mass is obtained. Numerical results are compared with data published in the specialized literature for different thrusters. Also, a sensitivity study is carried out regarding variables such as resistivity and plasma emissivity in the arc. Finally, the most relevant variables regarding the prediction of the ablated mass, the bit impulse and the specific impulse are identified Fil: Gómez, Emmanuel Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Estudios Avanzados en Ingeniería y Tecnología. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto de Estudios Avanzados en Ingeniería y Tecnología; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Departamento de Aeronáutica; Argentina Fil: Elaskar, Sergio Amado. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Departamento de Aeronáutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Estudios Avanzados en Ingeniería y Tecnología. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto de Estudios Avanzados en Ingeniería y Tecnología; Argentina

Maestría en Ciencias De La Ingeniería - Mención Aeroespacial En la década del ’90 se comenzó nuevamente a poner énfasis en diseñar satélites de bajo peso, los cuales además de bajar costos y tiempos de desarrollo, sean sencillos y robustos. En tal sentido, la idea general es poner en órbita constelaciones de micro o nano-satélites (masas inferiores a 50 y 10 kilogramos de peso respectivamente), teniendo capacidades individuales de maniobra para el vuelo en formación, los cuales a su vez puedan tener asignadas funciones de operación individuales o grupales. Es en este punto donde los Propulsores de Plasma Pulsantes ablativos (APPT por sus siglas en inglés) toman lugar debido a su simpleza constructiva, alto impulso específico, bajo impulso unitario, bajo peso y requerimientos de potencia, además de no necesitar empaquetamiento de combustible. En este trabajo, y de acuerdo a los modelos electromecánicos inestacionarios, se proponen dos modelos a partir de los cuales se simula a los APPT con el objetivo de caracterizar su performance. Se obtiene numéricamente la masa ablacionada, el bit de impulso, el impulso específico y el rendimiento propulsivo, entre otros, y se compara y valida con resultados experimentales indicados en la literatura especializada. En los modelos propuestos en este trabajo se incorpora la ecuación de la energía al sistema de ecuaciones original, lo cual agrega la temperatura del plasma como variable temporal al modelo. Para obtener la densidad de partículas de electrones del plasma en función del tiempo, se utiliza la ecuación de Saha considerando al plasma en Equilibrio Termodinámico Local. Se realiza un análisis de sensibilidad de ambos modelos respecto a variables eléctricas y geométricas prestando especial atención en su efecto sobre la masa ablacionada, el bit de impulso, el impulso específico y el rendimiento propulsivo. Por último, y utilizando algoritmos genéticos, se lleva a cabo el proceso de optimización de variables eléctricas, geométricas o ambas, utilizando uno de los modelos propuestos. Se analizan dos casos, optimización individual, es decir, de una sola función objetivo; y optimización múltiple o de mas de una función objetivo. Se interpretan los resultados y se identifican tendencias en cuanto a obtener un diseño óptimo de un APPT de teflón. Fil: Gomez, Emmanuel Walter. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina. Fil: Gomez, Emmanuel Walter. Fuerza Aérea Argentina. Universidad de la Defensa Nacional. Centro Regional Universitario Córdoba IUA; Argentina.

Background: Infants less than 6 months of age are at high risk for influenza disease and influenza-related complications, but no vaccine is licensed for this population. Methods: A double-blind, randomized, placebo-controlled trial was conducted in 1375 healthy US infants 6 to 12 weeks of age. Subjects received 2 doses of trivalent inactivated influenza vaccine (TIV, Fluzone, sanofi pasteur; N = 915) or placebo (N = 460) 1 month apart in combination with indicated concomitant vaccines. Solicited adverse events were collected for 7 days following vaccination, and unsolicited adverse events for 28 days. Hemagglutination-inhibition antibodies to all 3 vaccine strains were measured following the second TIV/placebo dose. Results: No significant differences were seen between TIV and placebo groups for any safety outcome. Fever ≥38°C within 3 days of vaccination was seen in 11.2% versus 11.7% of TIV versus placebo recipients. Serious adverse events within 28 days were reported in 1.9% of TIV and 1.5% of placebo recipients. Antibody responses to childhood vaccines were similar in both groups. Increased influenza-specific antibody responses in TIV recipients compared with placebo recipients were seen against all 3 strains in TIV recipients (P < 0.001), with better responses to influenza A strains noted. Reciprocal geometrical mean titer to H1N1, H3N2, and B were 33, 95, and 11 in TIV recipients versus 7, 9, and 5 for placebo recipients. Over 90% of TIV recipients had antibody ≥ 1:40 for at least 1 vaccine strain and 49.6% for 2 strains, versus 16.4% and 0.9% in placebo-recipients. Conclusions: TIV administered to young infants beginning at 6 to 12 weeks of age is safe and immunogenic.

Vibrio cholerae, the causative agent of the devastating diarrheal disease cholera, can form biofilms on diverse biotic and abiotic surfaces. Biofilm formation is important for the survival of this organism both in its natural environment and in the human host. Development of V. cholerae biofilms are regulated by complex regulatory networks that respond to environmental signals. One of these signals, norspermidine, is a polyamine that enhances biofilm formation via the NspS/MbaA signaling system. In this work, we have investigated the role of the polyamine spermidine in regulating biofilm formation in V. cholerae. We show that spermidine import requires PotD1, an ortholog of the periplasmic substrate-binding protein of the spermidine transport system in Escherichia coli. We also show that deletion of the potD1 gene results in a significant increase in biofilm formation. We hypothesize that spermidine imported into the cell hinders biofilm formation. Exogenous spermidine further reduces biofilm formation in a PotD1-independent, but NspS/MbaA-dependent, manner. Our results suggest that polyamines affect biofilm formation in V. cholerae via multiple pathways involving both transport and signaling networks.

This study addressed two aims: (1) to assess the level of depressive symptoms among pregnant, HIV-infected racial and ethnic minority women and (2) to identify potentially modifiable factors associated with prenatal depression in order to foster proactive clinical screening and intervention for these women. Baseline interview data collected from HIV-infected women participating in the Perinatal Guidelines Evaluation Project were analyzed. Participants were from prenatal clinics in four areas representative of the U. S. HIV/AIDS epidemic among women. Of the final sample (n = 307), 280 were minorities (218 blacks [African American and Caribbean], 62 Hispanic). Standardized interviews assessed potential psychosocial factors associated with pregnancy-related depression and psychological distress (life stressors, inadequate social support, and ineffective coping skills) in a population for whom little work has been done. Depressive symptomatology was considerable, despite excluding somatic items in order to avoid confounding from prenatal or HIV-related physical symptoms. The psychosocial factors significantly predicted the level of prenatal depressive symptoms beyond the effects of demographic and health-related factors. Perceived stress, social isolation, and disengagement coping were associated with greater depression, positive partner support with lower depression. These findings demonstrate that psychosocial and behavioral factors amenable to clinical intervention are associated with prenatal depression among women of color with HIV. Routine screening to identify those currently depressed or at risk for depression should be integrated into prenatal HIV-care settings to target issues most needing intervention.

Anthrax Vaccine Adsorbed (AVA) vaccination protects against anthrax infection by eliciting a neutralizing antibody response. However, protective antibody titers are not observed in human sera until at least three vaccinations have been administered over six months. Even then, humoral responses to AVA do not provide long-term immunity without an annual booster, presenting a serious challenge in public health. We followed six healthy volunteers over the standard five-dose, 18-month AVA schedule to characterize immunoglobulin genetics during vaccination. Plasmablasts were isolated one week after each vaccination and natively-paired heavy- and light-chain immunoglobulin mRNA were sequenced. Immunoglobulin sequences were analyzed for mutations and clonal evolution. After primary vaccination, the average mutation frequency of observed plasmablast lineages indicated they were derived from previously affinity matured B cells (6.1–7.7%). Many sequences had very high mutation frequencies (>10%), a characteristic that has been linked to multiple antigen exposures. We synthesized antibodies from these lineages and tested them against a panel of human antigens. While they had little to no affinity to anthrax antigens, they displayed significant affinity to a variety of autoantigens. These memory lineages were non-persistent, and we observed naïve B cell activation after secondary vaccination. We tested antibodies from naïve-derived lineages first observed after secondary vaccination and found these to be anthrax-specific and non-autoreactive. Thus, while primary AVA vaccination elicits a robust memory response, it is non-protective and delays anthrax-specific naïve B cell recruitment until secondary vaccination.

Background: HIV adversely affects growth in children. Pediatric AIDS Clinical Trial Group (PACTG) protocols often use weight velocity [changes in weight z-score for age (WAZ)] as a part of the composite endpoint for phase II and III clinical trials. However, WAZ and height velocity (HAZ) have not been critically compared for their utility as part of the composite endpoint. Methods: HAZ and WAZ were compared to predict laboratory and clinical progression of HIV in a retrospective cohort study of HIV-infected children with data from PACTG Protocol 300. Results: In both bivariable and multivariable analyses, changes in HAZ were more closely linked to subsequent progression than WAZ. Children with improved HAZ were somewhat less likely to exhibit virological failure [odds ratio (OR), 0.76; 95% confidence interval (Cl) 0.51-1.14], than children with improved WAZ (OR, 1.45; 95% Cl, 0.99,2.11). Children who had improved HAZ were less likely to exhibit immunological failure (OR, 0.7; 95% CI, 0.49-1.00), than children with improved WAZ (OR, 1.13; 95% CI, 0.82-1.57). Children who had improved HAZ were less likely to have other forms of clinical progression of HIV (OR, 0.55; 95% Cl, 0.31-0.99), than children who had improved WAZ (OR, 1.0; 95% CI, 1.58-1.94). Conclusions: Increases in HAZ were associated with reduced risk of subsequent clinical progression and subsequent immune reconstitution and weakly associated with declines in HIV RNA. Changes in WAZ were not associated with laboratory outcomes relevant to pediatric HIV infection. Height velocity should be considered as a component of a composite clinical endpoint in future PACTG trials.