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Abstract Influenza virus infections pose a significant threat to global health. Vaccination is the main countermeasure against influenza virus spread, however, the effectiveness of vaccines is variable. Current seasonal influenza virus vaccines mostly rely on the immunodominant hemagglutinin (HA) glycoprotein on the viral surface, which usually leads to a narrow and strain-specific immune response. The HA undergoes constant antigenic drift, which can lead to a dramatic loss in vaccine effectiveness, requiring the annual reformulation and readministration of influenza virus vaccines. Recently, it has been demonstrated that the subdominant glycoprotein, neuraminidase (NA), is an attractive target for vaccine development. Here, we tested a newly developed recombinant influenza virus N1 neuraminidase vaccine candidate, named N1-MPP, adjuvanted with CpG 1018, a TLR9 agonist. Additionally, N2-MPP and B-NA-MPP vaccine constructs have been generated to cover the range of influenza viruses that are seasonally circulating in humans. These constructs have been characterized in vitro and in vivo regarding their functionality and protective potential. Furthermore, a trivalent NA-MPP mix was tested. No antigenic competition between the individual NA constructs was detected. By adjuvating the recombinant protein constructs with CpG 1018 it was possible to induce a strong and robust immune response against the NA, which provided full protection against morbidity and mortality after high lethal challenges in vivo. This study provides important insights for the development of a broadly protective NA-based influenza virus vaccine candidate.

Abstract The COVID-19 pandemic presents an unprecedented challenge to global public health. Rapid development and deployment of safe and effective vaccines are imperative to control the pandemic. In the current study, we applied our adjuvanted stable prefusion SARS-CoV-2 spike (S-2P)-based vaccine, MVC-COV1901, to hamster models to demonstrate immunogenicity and protection from virus challenge. Golden Syrian hamsters immunized intramuscularly with two injections of 1 µg or 5 µg of S-2P adjuvanted with CpG 1018 and aluminum hydroxide (alum) were challenged intranasally with SARS-CoV-2. Prior to virus challenge, the vaccine induced high levels of neutralizing antibodies with 10,000-fold higher IgG level and an average of 50-fold higher pseudovirus neutralizing titers in either dose groups than vehicle or adjuvant control groups. Six days after infection, vaccinated hamsters did not display any weight loss associated with infection and had significantly reduced lung pathology and most importantly, lung viral load levels were reduced to lower than detection limit compared to unvaccinated animals. Vaccination with either 1 μg or 5 μg of adjuvanted S-2P produced comparable immunogenicity and protection from infection. This study builds upon our previous results to support the clinical development of MVC-COV1901 as a safe, highly immunogenic, and protective COVID-19 vaccine.

In this paper, I look back to the vast area of communication sciences, that fi rst arrived in the university sphere by means of journalism subjects. In reality, one of the fi rst academic magazines in the area of communication sciences was a magazine concerning journalism. During the 1940´s and 1950´s, journalism research was at the center of the renowned studies by Lazarsfeld. In the years that follow, Journalism study´s dependence on sociological inquiries and content analysis was left behind in the explosion of studies that took place in the 1960´s and 70`s. In the more recent years, the explosion of studies of Journalism was marked by the recourse to a multiplicity of new methodologies (such as, for example, the ethno-methodological approach, discursive analysis, focus groups), by the emergence and growing infl uence of television, by the interest relating to journalism´s ideological role, as well as by the appearance of new paradigms for understanding the news.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern negatively impact the effectiveness of vaccines. In this study, we challenge hamsters with the delta variant after 2- or 3-dose inoculations with SARS-CoV-2 vaccines constructed from stabilized prefusion spike proteins (S-2P) of Wuhan (W) and beta (B) variants. Compared to 3 doses of W S-2P, 2 doses of W S-2P followed by a third dose of B S-2P induced the highest neutralizing antibody titer against live SARS-CoV-2 virus and enhanced neutralization of omicron variant pseudovirus. Reduced lung live virus titer and pathology suggested that all vaccination regimens protect hamsters from SARS-CoV-2 delta variant challenge., Competing Interests: Potential conflicts of interest. C. C., T.-Y. K., C.-C. W., W.-.H. T, C.-E. L., Y.-J. L., and M.-Y. L. are coinventors for US provisional patent applications 63/240,408, 63/240,080, 63/248,189. and 63/251,741. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

CpG-motif-containing oligodeoxynucleotides (CpG-ODN) activate innate immunity through Toll-Like Receptor (TLR) 9 signaling and generate local immune responses when delivered directly to the lung. Herein we describe pharmacological studies in mice, cynomolgus monkeys, and in human primary cells which support the development of DV281, a C-class CpG-ODN, as an inhaled aerosolized immunotherapeutic for lung cancer to be combined with an inhibitor of the anti-programmed cell death protein 1 (PD‑1) immune checkpoint. In vitro, DV281 potently induced Interferon (IFN)‑α from monkey and human peripheral blood mononuclear cells (PBMCs), stimulated interleukin‑6 production and proliferation in human B cells, and induced TLR9-dependent cytokine responses from mouse splenocytes. Intranasal delivery of DV281 to mice led to substantial but transient cytokine and chemokine responses in the lung. Lung responses to repeated intranasal DV281 were partially to fully reversible 2 weeks after the final dose and were absent in TLR9-deficient mice. Single escalating doses of aerosolized DV281 in monkeys induced dose-dependent induction of IFN-regulated genes in bronchoalveolar lavage cells and blood. In a repeat-dose safety study in monkeys, inhaled DV281 was well-tolerated, and findings were mechanism of action-related and non-adverse. Co-culture of human PBMC with DV281 and anti-PD‑1 antibody did not augment cytokine or cellular proliferation responses compared to DV281 alone, indicating that the combination did not lead to dysregulated cytokine responses. These studies support clinical development of inhaled aerosolized DV281 as a combination therapy with anti-PD‑1 antibody for lung cancer immunotherapy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Current asthma treatments address symptoms rather than the underlying disease pathophysiology, a better understanding of which has led to the identification of the Th2 high endotype. The activation of Toll-like receptors to induce Type I interferons directly in the lungs represents a novel therapeutic approach to reset this underlying Th2 pathophysiology with the potential to provide long-term disease modification. We present the nonclinical data and phase I clinical profile of an inhaled TLR9 agonist, AZD1419, a C-type CpG designed to induce interferon in the lung. In healthy volunteers, AZD1419 was found to be safe and well-tolerated. Target engagement in the lung was demonstrated at all dose levels tested. No evidence of tolerization or amplification of responses was evident on repeated dosing and 15.4 mg was defined as the maximum tolerated dose. AZD1419 clinical data supports its continued development as a potentially disease-modifying therapeutic in asthma., (© 2017 American Society for Clinical Pharmacology and Therapeutics.)

Immunostimulatory DNA containing unmethylated CpG motifs is recognized by Toll-like receptor 9, resulting in the activation of innate immune responses that subsequently amplify the adaptive-immune response. Advances in the characterization of Toll-like receptor 9 signaling have identified immunostimulatory sequences (ISS) with distinct biological activities. Numerous animal models have demonstrated that synthetic ISS are effective adjuvants that enhance both humoral and cellular immune responses in diverse indications, ranging from infectious disease to cancer and allergy. An added benefit supporting the use of ISS as a vaccine adjuvant is that the specific activation of a pathway critical to the regulation of the immune response results in minimal toxicity. To date, clinical testing has largely affirmed the potency and safety of ISS-adjuvanted vaccines.

The synthesis and characterization of a Hepatitis B virus vaccine (HBsIC-ISS) candidate composed of Hepatitis B surface antigen (HBsAg) bionanoparticles conjugated to multiple copies of immunostimulatory sequence oligodeoxynucleotides is presented. An efficient tangential flow filtration (TFF) method has been developed to purify the conjugated bionanoparticles from the excess conjugation reagents. The TFF technique presented can serve as a rapid and convenient alternative to current methods like ultracentrifugation for the separation of excess small molecule/polymeric conjugation reagents from chemically modified viruses and other viruslike particles.

The goal of this study was to isolate and expand tumor cells in culture that closely resemble invasive cells in primary breast carcinoma tissue. Based on the hypothesis that invasive tumor cells are released more readily upon digestion with connective tissue-degrading enzymes because they are not confined within a basement membrane, we have designed a novel procedure for their isolation. Using this method, we have successfully expanded in culture aneusomic tumor cells from several primary breast tumors. Twenty nine of 44 (66%) specimens processed yielded proliferative and passageable cultures of up to 2 x 10(7) cells. The original tumor tissue and cultures derived therefrom were compared for aneusomy and the abnormal expression of the erb-B2, p53, and bcl-2 gene products. Remarkable similarities were observed. However, some intratumor heterogeneity in chromosome content was found between touch preparations and cultured cells. Overexpression of erb-B2 was observed in the vast majority of cases (16 of 20), suggesting that this phenotype may be important for dysregulated proliferation in vitro. The simple and rapid method described in this report could enable routine expansion of primary breast tumors and provide adequate numbers of viable cells for studying and manipulating their functional characteristics.