MVA-CoV2-S vaccine candidate confers full protection from SARS-CoV-2 brain infection and damage in susceptible transgenic mice

The protective efficacy of vaccines against SARS-CoV-2 infection in the brain is yet unclear. Here, in the susceptible transgenic K18-hACE2 mouse model of severe COVID-19 disease, we report a detailed spatiotemporal description of the SARS-CoV-2 infection and replication in different areas of the brain. Remarkably, SARS-CoV-2 brain replication occurs primarily in neurons, producing important neuropathological alterations such as neuronal loss, incipient signs of neuroinflammation, and vascular damage in SARS-CoV-2 infected mice. Notably, one or two doses of a modified vaccinia virus Ankara (MVA) vector expressing the SARS-CoV-2 spike (S) protein (MVA-CoV2-S) conferred full protection against SARS-CoV-2 cerebral infection, preventing virus replication in all areas of the brain and its associated damage. This protection was maintained even after SARS-CoV-2 reinfection. To our knowledge, this is the first study of a COVID-19 vaccine candidate showing 100% efficacy against SARS-CoV-2 brain infection and damage, reinforcing the use of MVA-CoV2-S as a promising vaccine candidate against SARS-CoV-2/COVID-19, worth to move forward into clinical trials.The authors thank the Centro de Investigación en Sanidad Animal (CISA)-Instituto Nacional de Investigaciones Agrarias (INIA-CSIC) (Valdeolmos, Madrid, Spain) for the BSL-3 facilities. SARS-CoV-2 MAD6 virus isolate was kindly provided by José M. Honrubia and Dr. Luis Enjuanes (CNB-CSIC, Madrid, Spain). We also thank to Dr. Konstantin L. Levitsky for excellent technical assistance with the confocal acquisition. We thank the Spanish Research Council (CSIC) and the Spanish Ministry of Science and Innovation (MICINN) for continuous support. This research was supported by MCIN/Spanish Research Agency (AEI)/ 10.13039/501100011033 grants: PID2019-105995RB-I00 (J.T.-A. and J.V.), PID2020- 114481RB-I00 (J.G.-A. and M.E.), and PID2019-106410RB-I00 (J.L.-B.). Moreover, this research work was also funded by Red TerCel ISCIII, RD16/0011/0025 (J.T.-A.); Consejería de Salud y Familias, Junta de Andalucía Grant, PECOVID-0078-2020 (R.R.-L. and J.V.); Fondo COVID-19 grant COV20/00151 [Spanish Health Ministry, Instituto de Salud Carlos III (ISCIII)], Fondo Supera COVID-19 (Crue Universidades-Banco Santander) grant and CSIC grant 202120E079 (J.G.-A.); and CSIC grant 2020E84, La CaixaImpulse grant CF01-00008, Ferrovial and MAPFRE donations (M.E.). Additionally, we have also funding from the European Commission-NextGenerationEU, through CSIC's Global Health Platform (PTI Salud Global) (J.G.-A. and M.E.) and the European Research Council (ERC Advanced Grant PRJ201502629) (J.L.-B.).N

The Bacterial Mucosal Immunotherapy MV130 Protects Against SARS-CoV-2 Infection and Improves COVID-19 Vaccines Immunogenicity

COVID-19-specific vaccines are efficient prophylactic weapons against SARS-CoV-2 virus. However, boosting innate responses may represent an innovative way to immediately fight future emerging viral infections or boost vaccines. MV130 is a mucosal immunotherapy, based on a mixture of whole heat-inactivated bacteria, that has shown clinical efficacy against recurrent viral respiratory infections. Herein, we show that the prophylactic intranasal administration of this immunotherapy confers heterologous protection against SARS-CoV-2 infection in susceptible K18-hACE2 mice. Furthermore, in C57BL/6 mice, prophylactic administration of MV130 improves the immunogenicity of two different COVID-19 vaccine formulations targeting the SARS-CoV-2 spike (S) protein, inoculated either intramuscularly or intranasally. Independently of the vaccine candidate and vaccination route used, intranasal prophylaxis with MV130 boosted S-specific responses, including CD8+-T cell activation and the production of S-specific mucosal IgA antibodies. Therefore, the bacterial mucosal immunotherapy MV130 protects against SARS-CoV-2 infection and improves COVID-19 vaccines immunogenicity.CF was supported by AECC Foundation (INVES192DELF) and is currently funded by the Miguel Servet program (ID: CP20/00106) (ISCIII). IH-M receives the support of a fellowship from la Caixa Foundation (ID 100010434, fellowship code: LCF/BQ/IN17/11620074) and from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 713673. AJ-C is a postgraduate fellow of the City Council of Madrid at the Residencia de Estudiantes (2020–2021). GD is supported by an European Molecular Biology Organization (EMBO) Long-term fellowship (ALTF 379-2019). This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. Project number 892965. OL and JA-C acknowledge Comunidad de Madrid (Tec4Bio-CM, S2018/NMT-4443, FEDER). Work in OL laboratory was funded by CNIO with the support of the projects Y2018/BIO4747 and P2018/NMT4443 from Comunidad de Madrid and co-funded by the European Social Fund and the European Regional Development Fund. The CNIO is supported by the Instituto de Salud Carlos III (ISCIII). Work at CNB and CISA is funded by the Spanish Health Ministry, Instituto de Salud Carlos III (ISCIII), Fondo COVID-19 grant COV20/00151, and Fondo Supera COVID-19 (Crue Universidades-Banco Santander) (to JG-A). Work in the DS laboratory is funded by the CNIC; by the European Research Council (ERC-2016-Consolidator Grant 725091); by Agencia Estatal de Investigación (PID2019-108157RB); by Comunidad de Madrid (B2017/BMD-3733 Immunothercan-CM); by Fondo Solidario Juntos (Banco Santander); by a research agreement with Inmunotek S.L.; and by Fundació La Marató de TV3 (201723). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the MICINN, and the Pro CNIC Foundation.Peer reviewe

Herramientas de apoyo a la enseñanza y gestión administrativa en la Facultad de Geografía e Historia: hacia un sistema híbrido presencial-virtual (VI Edición)

Con este Proyecto de Innovación y Mejora de la Calidad Docente, de carácter institucional, se pretende dar continuidad a la etapa de innovación y formación docente que se inició el pasado Curso 2018-2019 en la Facultad de Geografía e Historia de la Universidad Complutense de Madrid, así como a las anteriores iniciativas de la Facultad de Geografía e Historia en materia de nuevas tecnologías. El objetivo de este proyecto, siguiendo la metodología de los seis años anteriores, ha pretendido promover en la Facultad una formación en el ámbito de la innovación educativa y de las nuevas tecnologías basada en: (i) la formación del Profesorado, del Personal de Administración y Servicios, y de estudiantes del Centro y (ii) en el intercambio de experiencias innovadoras entre representantes de estos colectivos, para poder hacer uso de las mismas en su desempeño docente, administrativo y formativo, respectivamente. El Proyecto, dirigido por el Vicedecano de Innovación, Nuevas Tecnologías y Comunicación de la Facultad, se adecua a las líneas prioritarias de la convocatoria Innova-Gestión Calidad, puesto que ha servido para profundizar en la innovación y en la mejora de la calidad docente-investigadora a través de programas formativos que, en la actualidad, constituyen objetivos prioritarios de la Estrategia UCM2020 de Investigación.Universidad Complutense de MadridDecanatoFac. de Geografía e HistoriaFALSEsubmitte

Herramientas de apoyo a la enseñanza y gestión administrativa en la Facultad de Geografía e Historia: hacia un sistema híbrido presencial-virtual

Con este Proyecto de Innovación y Mejora de la Calidad Docente, de carácter institucional, se pretende dar continuidad a la etapa de innovación y formación docente que se inició el pasado Curso 2018-2019 en la Facultad de Geografía e Historia de la Universidad Complutense de Madrid, así como a las anteriores iniciativas de la Facultad de Geografía e Historia en materia de nuevas tecnologías. El objetivo de este proyecto, siguiendo la metodología de los cuatro años anteriores, ha pretendido promover en la Facultad una formación en el ámbito de la innovación educativa y de las nuevas tecnologías basada en: (i) la formación del Profesorado, del Personal de Administración y Servicios, y de estudiantes del Centro y (ii) en el intercambio de experiencias innovadoras entre representantes de estos colectivos, para poder hacer uso de las mismas en su desempeño docente, administrativo y formativo, respectivamente. El Proyecto, dirigido por el Vicedecano de Innovación, Nuevas Tecnologías y Comunicación de la Facultad, se adecua a las líneas prioritarias de la convocatoria Innova-Gestión Calidad, puesto que ha servido para profundizar en la innovación y en la mejora de la calidad docente-investigadora a través de programas formativos que, en la actualidad, constituyen objetivos prioritarios de la Estrategia UCM2020 de Investigación

First partial skeleton of a 1.34-million-year-old Paranthropus boisei from Bed II, Olduvai Gorge, Tanzania.

Recent excavations in Level 4 at BK (Bed II, Olduvai Gorge, Tanzania) have yielded nine hominin teeth, a distal humerus fragment, a proximal radius with much of its shaft, a femur shaft, and a tibia shaft fragment (cataloged collectively as OH 80). Those elements identified more specifically than to simply Hominidae gen. et sp. indet are attributed to Paranthropus boisei. Before this study, incontrovertible P. boisei partial skeletons, for which postcranial remains occurred in association with taxonomically diagnostic craniodental remains, were unknown. Thus, OH 80 stands as the first unambiguous, dentally associated Paranthropus partial skeleton from East Africa. The morphology and size of its constituent parts suggest that the fossils derived from an extremely robust individual who, at 1.338±0.024 Ma (1 sigma), represents one of the most recent occurrences of Paranthropus before its extinction in East Africa

The origin and evolution of maize in the Southwestern United States

The origin of maize (Zea mays mays) in the US Southwest remains contentious, with conflicting archaeological data supporting either coastal1,​2,​3,​4 or highland5,6 routes of diffusion of maize into the United States. Furthermore, the genetics of adaptation to the new environmental and cultural context of the Southwest is largely uncharacterized7. To address these issues, we compared nuclear DNA from 32 archaeological maize samples spanning 6,000 years of evolution to modern landraces. We found that the initial diffusion of maize into the Southwest about 4,000 years ago is likely to have occurred along a highland route, followed by gene flow from a lowland coastal maize beginning at least 2,000 years ago. Our population genetic analysis also enabled us to differentiate selection during domestication for adaptation to the climatic and cultural environment of the Southwest, identifying adaptation loci relevant to drought tolerance and sugar content.No Full Tex

Cross-sectional properties of femoral 50% sections of OH80 and KNM-ER 1808 (<i>Homo erectus</i>).

<p>CA, cortical area; MA, medullary area; TA, total periosteal area; %CA, [(CA/TA) · 100); Ix, second moment of area about X (ML) axis (AP bending rigidity); Iy, second moment of area about y (AP) axis (ML bending rigidity); J, polar second moment of area. Areas in mm², second moments of area in mm⁴.</p>*<p>Measurements taken directly on the proximal break of the shaft at the mid-section.</p

Ulna (OH36) found in upper Bed II and attributed to Paranthropus (upper) compared to the OH80-11 radius (lower) (Photo: Mario Torquemada).

<p>Ulna (OH36) found in upper Bed II and attributed to Paranthropus (upper) compared to the OH80-11 radius (lower) (Photo: Mario Torquemada).</p

The right femur (OH 80-12; left side of image) and right radius (OH 80-11; right side of image) of the OH 80 hominin from Level 4 at the BK site.

<p>Both fossils are shown in posterior view; superior is at the top of the image; the bar scale = 1 cm.</p