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Abstract The development of an effective AIDS vaccine remains a challenge. Nucleoside-modified mRNAs formulated in lipid nanoparticles (mRNA-LNP) have proved to be a potent mode of immunization against infectious diseases in preclinical studies, and are being tested for SARS-CoV-2 in humans. A critical question is how mRNA-LNP vaccine immunogenicity compares to that of traditional adjuvanted protein vaccines in primates. Here, we show that mRNA-LNP immunization compared to protein immunization elicits either the same or superior magnitude and breadth of HIV-1 Env-specific polyfunctional antibodies. Immunization with mRNA-LNP encoding Zika premembrane and envelope or HIV-1 Env gp160 induces durable neutralizing antibodies for at least 41 weeks. Doses of mRNA-LNP as low as 5 μg are immunogenic in macaques. Thus, mRNA-LNP can be used to rapidly generate single or multi-component vaccines, such as sequential vaccines needed to protect against HIV-1 infection. Such vaccines would be as or more immunogenic than adjuvanted recombinant protein vaccines in primates.

ABSTRACT Each year, >180,000 infants become infected via mother-to-child transmission (MTCT) of HIV despite the availability of effective maternal antiretroviral treatments, underlining the need for a maternal HIV vaccine. We characterized 224 maternal HIV envelope (Env)-specific IgG monoclonal antibodies (MAbs) from seven nontransmitting and transmitting HIV-infected U.S. and Malawian mothers and examined their neutralization activities against nontransmitted autologous circulating viruses and infant-transmitted founder (infant-T/F) viruses. Only a small subset of maternal viruses, 3 of 72 (4%), were weakly neutralized by maternal linear V3 epitope-specific IgG MAbs, whereas 6 out of 6 (100%) infant-T/F viruses were neutralization resistant to these V3-specific IgG MAbs. We also show that maternal-plasma broadly neutralizing antibody (bNAb) responses targeting the V3 glycan supersite in a transmitting woman may have selected for an N332 V3 glycan neutralization-resistant infant-T/F virus. These data have important implications for bNAb-eliciting vaccines and passively administered bNAbs in the setting of MTCT. IMPORTANCE Efforts to eliminate MTCT of HIV with antiretroviral therapy (ART) have met little success, with >180,000 infant infections each year worldwide. It is therefore likely that additional immunologic strategies that can synergize with ART will be required to eliminate MTCT of HIV. To this end, understanding the role of maternal HIV Env-specific IgG antibodies in the setting of MTCT is crucial. In this study, we found that maternal-plasma broadly neutralizing antibody (bNAb) responses can select for T/F viruses that initiate infection in infants. We propose that clinical trials testing the efficacy of single bNAb specificities should not include HIV-infected pregnant women, as a single bNAb might select for neutralization-resistant infant-T/F viruses.

Within the Drosophila embryo, two related bHLH-PAS proteins, Single-minded and Trachealess, control development of the central nervous system midline and the trachea, respectively. These two proteins are bHLH-PAS transcription factors and independently form heterodimers with another bHLH-PAS protein, Tango. During early embryogenesis, expression of Single-minded is restricted to the midline and Trachealess to the trachea and salivary glands, whereas Tango is ubiquitously expressed. Both Single-minded/Tango and Trachealess/Tango heterodimers bind to the same DNA sequence, called the CNS midline element (CME) within cis-regulatory sequences of downstream target genes. While Single-minded/Tango and Trachealess/Tango activate some of the same genes in their respective tissues during embryogenesis, they also activate a number of different genes restricted to only certain tissues. The goal of this research is to understand how these two related heterodimers bind different enhancers to activate different genes, thereby regulating the development of functionally diverse tissues. Existing data indicates that Single-minded and Trachealess may bind to different co-factors restricted to various tissues, causing them to interact with the CME only within certain sequence contexts. This would lead to the activation of different target genes in different cell types. To understand how the context surrounding the CME is recognized by different bHLH-PAS heterodimers and their co-factors, we identified and analyzed novel enhancers that drive midline and/or tracheal expression and compared them to previously characterized enhancers. In addition, we tested expression of synthetic reporter genes containing the CME flanked by different sequences. Taken together, these experiments identify elements overrepresented within midline and tracheal enhancers and suggest that sequences immediately surrounding a CME help dictate whether a gene is expressed in the midline or trachea.

Definir la estructura de una aplicación móvil (app) para el estudio de una lengua extranjera (LE) implica recuperar principios de aprendizaje lingüístico en interacción con los procesos subyacentes a los entornos digitales. Con base en esta premisa, aquí se muestra el recorrido teórico y pedagógico que siguió el equipo de diseño de una app educativa para el aprendizaje del italiano. Se describen, en primera instancia, los criterios de contribución de la app a las necesidades institucionales, en un momento de emergencia sanitaria que incentiva la creación de nuevas mediaciones de apoyo al aprendizaje lingüístico. Posteriormente, se señalan los lineamientos didácticos y tecno-pedagógicos considerados para establecer la estructura de la app, sobre una base curricular integrada por competencias que afrontan los retos de aprendizaje de una lengua próxima al español. Se mostrará, finalmente, la estructura de la app y un modelo de secuencia interactiva de aprendizaje.

Con el objetivo de determinar la flora normal aerobia, cloacal y nasal de la tortuga lora (Lepidochelys olivacea ), entre los meses de julio y agosto del 2002,se colectaron muestras bacteriológicas de 45 quelonios aparentemente sanos,durante el desove en Playa Nancite,Parque Nacional Santa Rosa, Costa Rica, a través del uso de hisopos estériles que se introdujeron en la cloaca y en uno de los conductos nasales. De las muestras recolectadas se obtuvieron e identificaron un total de 99 aislamientos, incluyendo 10 grupos de Gram-negativos y 5 de Gram-positivos. De cada tortuga se obtuvo un promedio de 0.7 bacterias de la cloaca y 1.4 de las cavidades nasales. Las bacterias más frecuente halladas fueron Aeromonas spp.(13/45) y Citrobacter freundi (6/45) en la cloaca, y Bacillus spp. (32/45),Staphylococcus aureus (6/45)y Corynebacterium spp.(5/45)en las cavidades nasales. En este investigación, la flora microbiana de las tortugas lora resultó constituida por microorganismos potencialmente patógenos para el ser humano y las tortugas.Cloacal and nasal bacterial flora of Lepidochelys olivacea (Testudines: Cheloniidae) from the North Pacific coast of Costa Rica.The aerobic cloacal and nasal bacterial flora of 45 apparently healthy female olive ridley sea turtles (Lepidochelys olivacea )was studied at Nancite nesting beach,in Santa Rosa National Park (Costa Rican North Pacific)during July and August 2002.Bacterial samples were obtained by inserting sterile swabs directly into the cloaca and the nasal cavities of the turtles.Ninety-nine aerobic bacterial isolates, including 10 Gram-negative and 5 Gram-positive bacteria, were recovered.The most common bacteria cultured were Aeromonas spp. (13/45) and Citrobacter freundi (6/45)from cloacal samples and Bacillus spp.(32/45), Staphylococcus aureus (6/45)and Corynebacterium spp.(5/45)from nasal ducts.The results of the present study showed that the aerobic bacterial flora of nesting female olive ridleys was composed of several potential human and animal microbe pathogens.Rev.Biol.Trop.54(1):43-48.Epub 2006 Mar 31.