Microneedle array delivered recombinant coronavirus vaccines: Immunogenicity and rapid translational development

Background: Coronaviruses pose a serious threat to global health as evidenced by Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and COVID-19. SARS Coronavirus (SARS-CoV), MERS Coronavirus (MERS-CoV), and the novel coronavirus, previously dubbed 2019-nCoV, and now officially named SARS-CoV-2, are the causative agents of the SARS, MERS, and COVID-19 disease outbreaks, respectively. Safe vaccines that rapidly induce potent and long-lasting virus-specific immune responses against these infectious agents are urgently needed

Microarray patches enable the development of skin-targeted vaccines against COVID-19

The COVID-19 pandemic is a serious threat to global health and the global economy. The ongoing race to develop a safe and efficacious vaccine to prevent infection by SARS-CoV-2, the causative agent for COVID-19, highlights the importance of vaccination to combat infectious pathogens. The highly accessible cutaneous microenvironment is an ideal target for vaccination since the skin harbors a high density of antigen-presenting cells and immune accessory cells with broad innate immune functions. Microarray patches (MAPs) are an attractive intracutaneous biocargo delivery system that enables safe, reproducible, and controlled administration of vaccine components (antigens, with or without adjuvants) to defined skin microenvironments. This review describes the structure of the SARS-CoV-2 virus and relevant antigenic targets for vaccination, summarizes key concepts of skin immunobiology in the context of prophylactic immunization, and presents an overview of MAP-mediated cutaneous vaccine delivery. Concluding remarks on MAP-based skin immunization are provided to contribute to the rational development of safe and effective MAP-delivered vaccines against emerging infectious diseases, including COVID-19

Preventative Vaccines for Zika Virus Outbreak: Preliminary Evaluation

Since it emerged in Brazil in May 2015, the mosquito-borne Zika virus (ZIKV) has raised global concern due to its association with a significant rise in the number of infants born with microcephaly and neurological disorders such as Guillain-Barré syndrome. We developed prototype subunit and adenoviral-based Zika vaccines encoding the extracellular portion of the ZIKV envelope gene (E) fused to the T4 fibritin foldon trimerization domain (Efl). The subunit vaccine was delivered intradermally through carboxymethyl cellulose microneedle array (MNA). The immunogenicity of these two vaccines, named Ad5.ZIKV-Efl and ZIKV-rEfl, was tested in C57BL/6 mice. Prime/boost immunization regimen was associated with induction of a ZIKV-specific antibody response, which provided neutralizing immunity. Moreover, protection was evaluated in seven-day-old pups after virulent ZIKV intraperitoneal challenge. Pups born to mice immunized with Ad5.ZIKV-Efl were all protected against lethal challenge infection without weight loss or neurological signs, while pups born to dams immunized with MNA-ZIKV-rEfl were partially protected (50%). No protection was seen in pups born to phosphate buffered saline-immunized mice. This study illustrates the preliminary efficacy of the E ZIKV antigen vaccination in controlling ZIKV infectivity, providing a promising candidate vaccine and antigen format for the prevention of Zika virus disease

Molecular and imaging techniques for bacterial biofilms in joint arthroplasty infections

Biofilm formation on surfaces is an ancient and integral strategy for bacterial survival. Billions of years of adaptation provide microbes with the ability to colonize any surface, including those used in orthopaedic surgery. Although remarkable progress has been made in the treatment of orthopaedic diseases with implanted prostheses, infection rates remain between 1% and 2%, and are higher for revision surgeries. The chronic nature of implant infections, their nonresponsiveness to antibiotics, and their frequent culture negativity can be explained by the biofilm paradigm of infectious disease. However, the role of biofilms in orthopaedic implant infections and aseptic loosening is controversial. To address these issues, we developed molecular diagnostic and confocal imaging techniques to identify and characterize biofilms associated with infected implants. We designed PCR and reverse transcription (RT)-PCR-based assays that can be used to detect bacterial infections associated with culture-negative joint effusions that distinguish between physiologically active Staphylococcus aureus and Staphylococcus epidermidis. Using clinical isolates of Pseudomonas aeruginosa, we constructed a series of reporter strains expressing colored fluorescent proteins to observe biofilms growing on 316L stainless steel and titanium orthopaedic screws. Three-dimensional structures of Pseudomonas aeruginosa and staphylococci biofilms growing on the screws were documented using confocal microscopy. The application of these tools for clinical diagnosis and biofilm research in animal and in vitro models is discussed

Cassini plasma spectrometer measurements of Jovian bow shock structure

International audienceThe Cassini spacecraft on its way to Saturn flew by Jupiter and crossed its bow shock more than forty times on the dusk-side of the planet, whereas the early missions targeting Jupiter explored the dawnside. Here we report the first results concerning these bow shock crossings, based on the measurements of the Cassini Plasma Spectrometer (CAPS), the magnetometer, and the radio and plasma wave science (RPWS) instrument. We present data for five bow shock crossings, one at about 1920 local time (LT), the other four between 2100 and 2130 LT, 47.5°-50° beyond terminator. During the flyby the solar activity was high and variable. The measurements confirm that the Jovian bow shock is huge, extending over 700 RJ down the flank; Cassini was the first to observe such distant shock features. The bow shock was turbulent and very dynamic and magnetic fluctuations were superimposed on the shock; the downstream ion distributions exhibited bimodal structure time to time. For all bow shock crossings the onset of ion thermalization was a clear shock signature supported by an electrostatic wave signal; thermalization can be used as a signature of the shock location even in those cases when the field data are rather smeared. The strength of the shock potential weakened toward more distant regions even if the local Mach number did not decrease. Reflected protons were not detected upstream above our current sensitivity limit, but the incoming solar wind fluctuated in the foot region. We argue that the Jovian bow shock is not always in a steady state, and some of the observations might be connected with this fact

A pre-shock event at Jupiter on 30 January 2001

International audienceIn this paper we analyze a pre-shock event that we observed in the foot region of the quasi-parallel bow shock (BS) that the Cassini spacecraft crossed on 30 January 2001, at about 1030 UT. Before crossing the BS, the incoming solar wind first decelerated, and then the bulk velocity both of the proton and α components increased, the flow accelerated and decelerated, heated and cooled several times. We characterize the plasma in the foot using the data measured by the magnetometer, the radio and plasma wave science (RPWS) instrument, and the Cassini plasma spectrometer (CAPS) being carried onboard the Cassini spacecraft, and analyze the observations. We argue that the velocity and temperature changes can be caused by firehose instabilities excited by ions reflected from the shock. We investigate another possibility, shocklet formation, to account for the observed features, but conclude that this explanation seems to be less likely. In the foot we also identified both backstreaming electrons and ions and electrostatic waves in the 100-1000 Hz range very likely excited by the backstreaming electrons