An Overview on the Field of Micro- and Nanotechnologies for Synthetic Peptide-Based Vaccines

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Spatial-temporal excess mortality patterns of the 1918-1919 influenza pandemic in Spain

Background: The impact of socio-demographic factors and baseline health on the mortality burden of seasonal and pandemic influenza remains debated. Here we analyzed the spatial-temporal mortality patterns of the 1918 influenza pandemic in Spain, one of the countries of Europe that experienced the highest mortality burden. Methods: We analyzed monthly death rates from respiratory diseases and all-causes across 49 provinces of Spain, including the Canary and Balearic Islands, during the period January-1915 to June-1919. We estimated the influenza-related excess death rates and risk of death relative to baseline mortality by pandemic wave and province. We then explored the association between pandemic excess mortality rates and health and socio-demographic factors, which included population size and age structure, population density, infant mortality rates, baseline death rates, and urbanization. Results: Our analysis revealed high geographic heterogeneity in pandemic mortality impact. We identified 3 pandemic waves of varying timing and intensity covering the period from Jan-1918 to Jun-1919, with the highest pandemic-related excess mortality rates occurring during the months of October-November 1918 across all Spanish provinces. Cumulative excess mortality rates followed a south-north gradient after controlling for demographic factors, with the North experiencing highest excess mortality rates. A model that included latitude, population density, and the proportion of children living in provinces explained about 40% of the geographic variability in cumulative excess death rates during 1918-19, but different factors explained mortality variation in each wave. Conclusions: A substantial fraction of the variability in excess mortality rates across Spanish provinces remained unexplained, which suggests that other unidentified factors such as comorbidities, climate and background immunity may have affected the 1918-19 pandemic mortality rates. Further archeo-epidemiological research should concentrate on identifying settings with combined availability of local historical mortality records and information on the prevalence of underlying risk factors, or patient-level clinical data, to further clarify the drivers of 1918 pandemic influenza mortality.

Development of nucleic acid vaccines: use of self-amplifying RNA in lipid nanoparticles

Self-amplifying RNA or RNA replicon is a form of nucleic acid-based vaccine derived from either positive-strand or negative-strand RNA viruses. The gene sequences encoding structural proteins in these RNA viruses are replaced by mRNA encoding antigens of interest as well as by RNA polymerase for replication and transcription. This kind of vaccine has been successfully assayed with many different antigens as vaccines candidates, and has been shown to be potent in several animal species, including mice, nonhuman primates, and humans. A key challenge to realizing the broad potential of self-amplifying vaccines is the need for safe and effective delivery methods. Ideally, an RNA nanocarrier should provide protection from blood nucleases and extended blood circulation, which ultimately would increase the possibility of reaching the target tissue. The delivery system must then be internalized by the target cell and, upon receptor-mediated endocytosis, must be able to escape from the endosomal compartment into the cell cytoplasm, where the RNA machinery is located, while avoiding degradation by lysosomal enzymes. Further, delivery systems for systemic administration ought to be well tolerated upon administration. They should be safe, enabling the multiadministration treatment modalities required for improved clinical outcomes and, from a developmental point of view, production of large batches with reproducible specifications is also desirable. In this review, the concept of self-amplifying RNA vaccines and the most promising lipid-based delivery systems are discussed.

Dynamics of Streptococcus pneumoniae Serotypes Causing Acute Otitis Media Isolated from Children with Spontaneous Middle-Ear Drainage over a 12-Year Period (1999–2010) in a Region of Northern Spain

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La respuesta del Personal Sanitario de España durante las campañas de vacunación antigripal

La infección vírica causada por el virus gripal o influenza representa una importante carga de enfermedad a nivel mundial y es responsable de una elevada morbilidad y mortalidad especialmente en ciertos grupos de riesgo. La vacunación constituye un elemento fundamental y es la principal medida preventiva para hacer frente a la gripe y sus complicaciones. El personal sanitario puede actuar como agente transmisor de la infección nosocomial, por este motivo se encuentra incluido en los grupos de riesgo en los que la vacunación frente a la gripe está indicada anualmente siempre y cuando no presente contraindicaciones. Dada su relevancia, se realizó una revisión bibliográfica, en las principales bases de datos electrónicas, para conocer la cobertura de vacunación antigripal (estacional y pandémica) del personal sanitario de España así como analizar las estrategias adoptadas con el fin de aumentar la cobertura de vacunación. La cobertura de vacunación de los profesionales sanitarios de España es baja, siendo menor para la gripe A (H1N1) que para la gripe estacional. Entre el colectivo de profesionales, los médicos tienen mayor cobertura seguido del personal de enfermería. El principal motivo para vacunarse es la autoprotección así como evitar el contagio de sus pacientes, y para no vacunarse dudar sobre la seguridad de la vacuna. La falta de información acerca de estrategias para aumentar la cobertura antigripal y la baja cobertura de este colectivo hacen necesario el desarrollo de más estudios para poder determinar el diseño e intervenciones de las campañas de vacunación antigripal.

Vacunas profilácticas frente al VPH

Actualmente sólo existen dos vacunas disponibles para la prevención primaria frente al virus del papiloma humano, Gardasil® y Cervarix®. Ambas vacunas ofrecen una alta protección contra los genotipos 16 y 18 del papillomavirus, que son los responsables de más del 70% de los cánceres de cérvix, segunda causa de mortalidad por cáncer a nivel mundial en mujeres. Además, Gardasil®, ofrece una protección del 99% para las mujeres y del 89,4% para los hombre, frente a los genotipos 6 y 11 del virus, responsables del 90% de las verrugas genitales. Uno de los principales obstáculos para su uso generalizado es su elevado coste, por ello, los ensayos clínicos se dirigen a conseguir una inmunogenicidad eficaz con el menor número de dosis. Cervarix® se comercializa en Europa con una pauta de dos dosis en niñas de 9 a 14 años, con una inmunogenicidad de 48 meses. Gardasil® ha sido autorizada para su comercialización para una pauta de dos dosis en niñas/os de 9 a 13 años, con una imunogenicidad de 36 meses. Ambas vacunas han despertado una gran controversia en los últimos tiempos, por este motivo se están realizando continuos estudios de control que, hasta la fecha, avalan su seguridad. La falta de información sobre las vacunas, los escasos programas de sensibilización y las dudas sobre su seguridad han dificultado su aceptación. El papel de la enfermera es clave en este aspecto para fomentar la vacunación, a través de actividades dirigidas hacía la promoción y prevención frente al virus del papiloma humano.

El VIH: el origen, la patología y el tratamiento

The HIV (Human Immunodeficiency Virus) is a very important disease in the world, with approximately 35 million people infected. In this study we have tried to expose the main characters of the virus, explaining the disease and the illness associated to the HIV. Besides, we have explained the antiretroviral treatments that are the most important weapon against the HIV. However, any of these treatments do not eliminate the HIV in the human body. For this reason, we have been looking for the new treatments and researches that have been development in the last years, including vaccines and genetic resistance. In addition, we have described the situation of the SIV (Simian Immunodeficiency Virus) in Africa, because it is the origin of the disease. The prevalence of the virus in primates population is something that have being studied for the last years, because it could be a new threat to the human population. Finally, we have proposed the researches lines that seems to be more effective and the ones that, in a future, could eliminate the virus in the human body.

HIV-1 Capture and Transmission by Dendritic Cells: The Role of Viral Glycolipids and the Cellular Receptor Siglec-1

Dendritic cells (DCs) are essential in order to combat invading viruses and trigger antiviral responses. Paradoxically, in the case of HIV-1, DCs might contribute to viral pathogenesis through trans-infection, a mechanism that promotes viral capture and transmission to target cells, especially after DC maturation. In this review, we highlight recent evidence identifying sialyllactose-containing gangliosides in the viral membrane and the cellular lectin Siglec-1 as critical determinants for HIV-1 capture and storage by mature DCs and for DC-mediated trans-infection of T cells. In contrast, DC-SIGN, long considered to be the main receptor for DC capture of HIV-1, plays a minor role in mature DC-mediated HIV-1 capture and trans-infection.

Lipid Nanoparticles as Carriers for RNAi against Viral Infections: Current Status and Future Perspectives

The efforts made to develop RNAi-based therapies have led to productive research in the field of infections in humans, such as hepatitis C virus (HCV), hepatitis B virus (HBV), human immunodeficiency virus (HIV), human cytomegalovirus (HCMV), herpetic keratitis, human papillomavirus, or influenza virus. Naked RNAi molecules are rapidly digested by nucleases in the serum, and due to their negative surface charge, entry into the cell cytoplasm is also hampered, which makes necessary the use of delivery systems to exploit the full potential of RNAi therapeutics. Lipid nanoparticles (LNP) represent one of the most widely used delivery systems for in vivo application of RNAi due to their relative safety and simplicity of production, joint with the enhanced payload and protection of encapsulated RNAs. Moreover, LNP may be functionalized to reach target cells, and they may be used to combine RNAi molecules with conventional drug substances to reduce resistance or improve efficiency. This review features the current application of LNP in RNAi mediated therapy against viral infections and aims to explore possible future lines of action in this field.

Long-Term Epidemiology of Streptococcus pneumoniae Serogroup 6 in a Region of Southern Europe with Special Reference to Serotype 6E

Streptococcus pneumoniae serotype 6E has recently been described, but its long-term epidemiology is not well known. From 1981-2013, 704 serogroup 6 clinical isolates were obtained in Gipuzkoa, Basque Country, Spain. All invasive and one in four non-invasive isolates were included. Overall, 75, 97, 51 and 45 serotypes 6A, 6B, 6C and 6E isolates, respectively, were detected. No serotype 6D isolates were identified. The prevalence of serotypes 6E and 6B, but not that of serotypes 6A and 6C, declined after the introduction of pneumococcal conjugate vaccines. Serotype 6E isolates showed the highest resistance rate. Most serotype 6E isolates were ST90.

Streptococcus pyogenes Pneumonia in Adults: Clinical Presentation and Molecular Characterization of Isolates 2006-2015

Introduction In the preantibiotic era Streptococcus pyogenes was a common cause of severe pneumonia but currently, except for postinfluenza complications, it is not considered a common cause of community-acquired pneumonia in adults. Aim and Material and Methods This study aimed to identify current clinical episodes of S. pyogenes pneumonia, its relationship with influenza virus circulation and the genotypes of the involved isolates during a decade in a Southern European region (Gipuzkoa, northern Spain). Molecular analysis of isolates included emm, multilocus-sequence typing, and superantigen profile determination. Results Forty episodes were detected (annual incidence 1.1 x 100,000 inhabitants, range 0.29-2.29). Thirty-seven episodes were community-acquired, 21 involved an invasive infection and 10 developed STSS. The associated mortality rate was 20%, with half of the patients dying within 24 hours after admission. Influenza coinfection was confirmed in four patients and suspected in another. The 52.5% of episodes occurred outside the influenza seasonal epidemic. The 67.5% of affected persons were elderly individuals and adults with severe comorbidities, although 13 patients had no comorbidities, 2 of them had a fatal outcome. Eleven clones were identified, the most prevalent being emm1/ST28 (43.6%) causing the most severe cases. Conclusions S. pyogenes pneumonia had a continuous presence frequently unrelated to influenza infection, being rapidly fatal even in previously healthy individuals.