Effect of remdesivir post-exposure prophylaxis and treatment on pathogenesis of measles in rhesus macaques.

Measles is a systemic disease initiated in the respiratory tract with widespread measles virus (MeV) infection of lymphoid tissue. Mortality can be substantial, but no licensed antiviral therapy is available. We evaluated both post-exposure prophylaxis and treatment with remdesivir, a broad-spectrum antiviral, using a well-characterized rhesus macaque model of measles.

Infection of Pro- and Anti-Inflammatory Macrophages by Wild Type and Vaccine Strains of Measles Virus: NLRP3 Inflammasome Activation Independent of Virus Production.

In humans and non-human primates, wild type (WT) measles virus (MeV) replicates extensively in lymphoid tissue and induces an innate response characteristic of NF-κB and inflammasome activation without type I interferon. In contrast, the live attenuated MeV vaccine (LAMV) replicates poorly in lymphoid tissue with little detectable in vivo cytokine production. To characterize the innate responses of macrophages to WT MeV and LAMV infection, we analyzed primary human monocyte-derived macrophages and phorbol myristic acid-matured monocytic THP-1 cells (M0) polarized to inflammatory (M1) and anti-inflammatory (M2) phenotypes 24 h after MeV infection.

Gut Microbiota of Obese Children Influences Inflammatory Mucosal Immune Pathways in the Respiratory Tract to Influenza Virus Infection: Optimization of an Ideal Duration of Microbial Colonization in a Gnotobiotic Pig Model.

The impact of obesity on the human microbiota, immune maturation, and influenza virus infection has not been yet established in natural host animal models of influenza. In this study, gnotobiotic (Gn) pigs were colonized with human fecal microbiota (HFM) of obese (oHFM) or healthy lean (hHFM) children and infected at different periods (2-, 3-, and 5-weeks post-transplantation) using a zoonotic influenza virus strain. The infected oHFM pigs were characterized by lower levels of Firmicutes (, and Streptococcus) and Actinobacteria (), which was associated with higher levels of Proteobacteria (Klebsiella), Bacteroidetes, and Verrucomicrobia () compared with the infected hHFM group ( < 0.

Continued Virus-Specific Antibody-Secreting Cell Production, Avidity Maturation and B Cell Evolution in Patients Hospitalized with COVID-19.

Understanding the development and sustainability of the virus-specific protective immune response to infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) remains incomplete with respect to the appearance and disappearance of virus-specific antibody-secreting cells (ASCs) in circulation. Therefore, we performed cross-sectional and longitudinal analyses of peripheral blood mononuclear cells and plasma collected from 55 hospitalized patients up to 4 months after onset of COVID-19 symptoms. Spike (S)- and nucleocapsid (N)-specific IgM and IgG ASCs appeared within 2 weeks accompanied by flow cytometry increases in double negative plasmablasts consistent with a rapid extrafollicular B cell response.

Perceptions towards COVID-19 Vaccines and Willingness to Vaccinate in Nepal.

Vaccination is the most effective preventive measure of COVID-19 available at present, but its success depends on the global accessibility of vaccines and the willingness of people to be vaccinated. As the vaccination rollouts are increasing worldwide, it is important to assess public perception and willingness towards vaccination, so that the aim of mass vaccination will be successful. This study aimed to understand public perception towards COVID-19 vaccines and their willingness to get vaccinated in Nepal.

Inhibition of elastase enhances the adjuvanticity of alum and promotes anti-SARS-CoV-2 systemic and mucosal immunity.

Alum, used as an adjuvant in injected vaccines, promotes T helper 2 (Th2) and serum antibody (Ab) responses. However, it fails to induce secretory immunoglobulin (Ig) A (SIgA) in mucosal tissues and is poor in inducing Th1 and cell-mediated immunity. Alum stimulates interleukin 1 (IL-1) and the recruitment of myeloid cells, including neutrophils.

Chitosan-adjuvanted Salmonella subunit nanoparticle vaccine for poultry delivered through drinking water and feed.

Poor induction of mucosal immunity in the intestines by current Salmonella vaccines is a challenge to the poultry industry. We prepared and tested an oral deliverable Salmonella subunit vaccine containing immunogenic outer membrane proteins (OMPs) and flagellin (F) protein loaded and F-protein surface coated chitosan nanoparticles (CS NPs) (OMPs-F-CS NPs). The OMPs-F-CS NPs had mean particle size distribution of 514 nm, high positive charge and spherical in shape.

A Nanoparticle-Poly(I:C) Combination Adjuvant Enhances the Breadth of the Immune Response to Inactivated Influenza Virus Vaccine in Pigs.

Intranasal vaccination elicits secretory IgA (SIgA) antibodies in the airways, which is required for cross-protection against influenza. To enhance the breadth of immunity induced by a killed swine influenza virus antigen (KAg) or conserved T cell and B cell peptides, we adsorbed the antigens together with the TLR3 agonist poly(I:C) electrostatically onto cationic alpha-D-glucan nanoparticles (Nano-11) resulting in Nano-11-KAg-poly(I:C) and Nano-11-peptides-poly(I:C) vaccines. In vitro, increased TNF-α and IL-1ß cytokine mRNA expression was observed in Nano-11-KAg-poly(I:C)-treated porcine monocyte-derived dendritic cells.

Poly(I:C) augments inactivated influenza virus-chitosan nanovaccine induced cell mediated immune response in pigs vaccinated intranasally.

To improve the innate and adaptive immune responses elicited by a killed/inactivated swine influenza virus antigen (KAg)-loaded chitosan nanoparticles (CS NPs-KAg), we used the adjuvant, poly(I:C). The formulated CS NPs-KAg and CS NPs-poly(I:C) had a net surface charge of +30.7 mV and +25.

Amish (Rural) vs. non-Amish (Urban) Infant Fecal Microbiotas Are Highly Diverse and Their Transplantation Lead to Differences in Mucosal Immune Maturation in a Humanized Germfree Piglet Model.

The gut microbiome plays an important role in the immune system development, maintenance of normal health status, and in disease progression. In this study, we comparatively examined the fecal microbiomes of Amish (rural) and non-Amish (urban) infants and investigated how they could affect the mucosal immune maturation in germ-free piglets that were inoculated with the two types of infant fecal microbiota (IFM). Differences in microbiome diversity and structure were noted between the two types of fecal microbiotas.

Pathogenicity and immunogenicity of attenuated porcine epidemic diarrhea virus PC22A strain in conventional weaned pigs.

Background: Porcine epidemic diarrhea virus (PEDV) causes diarrhea in all ages of pigs with 50-100% mortality rates in neonatal piglets. In the United States, inactivated and subunit PEDV vaccines for pregnant sows are available, but fail to induce sufficient protection in neonatal piglets farrowed from PEDV naïve sows. A safe and efficacious live attenuated vaccine that can prime mucosal immune responses is urgently needed.

Corn-derived alpha-D-glucan nanoparticles as adjuvant for intramuscular and intranasal immunization in pigs.

Adjuvant potential of positively charged corn-derived nanoparticles (Nano-11) was earlier revealed in mice. We evaluated its adjuvant role to electrostatically adsorbed inactivated/killed swine influenza virus antigen (KAg) (Nano-11 + KAg) in pigs. Nano-11 facilitated the uptake of KAg by antigen presenting cells and induced secretion of proinflammatory cytokines.

Liposomal nanoparticle-based conserved peptide influenza vaccine and monosodium urate crystal adjuvant elicit protective immune response in pigs.

Background: Influenza (flu) is a constant threat to humans and animals, and vaccination is one of the most effective ways to mitigate the disease. Due to incomplete protection induced by current flu vaccines, development of novel flu vaccine candidates is warranted to achieve greater efficacy against constantly evolving flu viruses.

Methods: In the present study, we used liposome nanoparticle (<200 nm diameter)-based subunit flu vaccine containing ten encapsulated highly conserved B and T cell epitope peptides to induce protective immune response against a zoonotic swine influenza A virus (SwIAV) H1N1 challenge infection in a pig model.

Mucosal Immunity and Protective Efficacy of Intranasal Inactivated Influenza Vaccine Is Improved by Chitosan Nanoparticle Delivery in Pigs.

Annually, swine influenza A virus (SwIAV) causes severe economic loss to swine industry. Currently used inactivated SwIAV vaccines administered by intramuscular injection provide homologous protection, but limited heterologous protection against constantly evolving field viruses, attributable to the induction of inadequate levels of mucosal IgA and cellular immune responses in the respiratory tract. A novel vaccine delivery platform using mucoadhesive chitosan nanoparticles (CNPs) administered through intranasal (IN) route has the potential to elicit strong mucosal and systemic immune responses in pigs.

Deletion of a 197-Amino-Acid Region in the N-Terminal Domain of Spike Protein Attenuates Porcine Epidemic Diarrhea Virus in Piglets.

We previously isolated a porcine epidemic diarrhea virus (PEDV) strain, PC177, by blind serial passaging of the intestinal contents of a diarrheic piglet in Vero cell culture. Compared with the highly virulent U.S.

Japanese encephalitis: Challenges and intervention opportunities in Nepal.

Japanese encephalitis (JE) is a mosquito borne zoonotic disease caused by JE virus (JEV). JE has been endemic in Terai region, the lowland plains of Nepal bordering India, since 1978. However, in recent years cases of JE has been continuously reported from high altitude zones of hills and mountains.