Evaluating the Zoonotic Potential of Non-Human Influenza D Virus

Influenza viruses are respiratory pathogens known to infect a wide variety of vertebrate species and cause annual epidemics in addition to sporadic pandemics. These viruses belong to the Orthomyxoviridae family and are divided into three genera – influenzas A, B, and C. In 2011, a novel virus sharing approximately 50% amino acid homology with human influenza C virus (ICV) was isolated from pigs showing symptoms of respiratory infection in Oklahoma. Further studies revealed that this newly isolated virus was unable to reassort with human ICV to produce viable progeny and exhibited no cross-recognition with human ICV polyclonal antibodies. These findings suggested the virus isolate was genetically and antigenically divergent from human ICV, thus a new genus within the Orthomyxoviridae family was established, termed influenza D virus (IDV). In 2017 and 2018, the Animal Influenza Ecology and Epidemiology Research Program at The Ohio State University collected nasal swabs and nasal wipes from swine being sold at jackpot shows and identified several IDV strains. To investigate the potential for IDV transmission to humans, we infected primary human nasal epithelial cells (hNECs) with three swine isolates of IDV (D/swine/Kentucky/17TOSU1262/2017, D/swine/Ohio/18TOSU0287/2018, and D/swine/Kentucky/17SW1262/2017) and determined infectious virus production and epithelial cell tropism at temperatures consistent with the upper (32˚C) and lower (37˚C) human respiratory tract. The IDV strains replicated to high infectious virus titer in MDCK cells and hNEC cultures, indicating they were capable of infecting cells of the human respiratory tract. A comparison of chemokine and cytokine induction in hNEC cultures following IDV infection demonstrated decreased expression in 50% of factors tested when compared to ICV infected cultures. High titer replication in conjunction with repression of the innate immune response suggests IDV is capable of human infection. These studies provide a better understanding of the ability of IDV to infect and cause disease in humans and suggest increased surveillance for this genus of influenza virus is necessary

Antibody attributes that predict the neutralization and effector function of polyclonal responses to SARS-CoV-2

BACKGROUND: While antibodies can provide significant protection from SARS-CoV-2 infection and disease sequelae, the specific attributes of the humoral response that contribute to immunity are incompletely defined. METHODS: We employ machine learning to relate characteristics of the polyclonal antibody response raised by natural infection to diverse antibody effector functions and neutralization potency with the goal of generating both accurate predictions of each activity based on antibody response profiles as well as insights into antibody mechanisms of action. RESULTS: To this end, antibody-mediated phagocytosis, cytotoxicity, complement deposition, and neutralization were accurately predicted from biophysical antibody profiles in both discovery and validation cohorts. These models identified SARS-CoV-2-specific IgM as a key predictor of neutralization activity whose mechanistic relevance was supported experimentally by depletion. CONCLUSIONS: Validated models of how different aspects of the humoral response relate to antiviral antibody activities suggest desirable attributes to recapitulate by vaccination or other antibody-based interventions

A Comparison of Retrospectively Reported and Ecological Momentary Assessment-Reported Perceived Social Support in Predicting Ecological Momentary Assessment-Reported Non-Suicidal Self-Injury

Introduction: Non-suicidal self-injury (NSSI) urges and behaviors are associated with lower perceived social support and related constructs (e.g., perceived rejection). However, no studies have examined the concordance of retrospective (baseline) and ecological momentary assessment (EMA) perceived social support assessments. Retrospective and EMA reports are often only weakly to moderately correlated; measurement approaches may, therefore, impact observed associations between variables. We tested whether average EMA-reported perceived emotional social support uniquely predicts EMA-reported NSSI urges and behaviors above baseline-reported retrospective self-report of perceived emotional social support alone. Methods: 93 young adults (ages 18-34) with past-month NSSI urges or behaviors and lifetime NSSI behaviors completed a semi-structured interview, self-report surveys, and a two-week EMA protocol. Results: Baseline- and EMA-reported perceived emotional social support were positively correlated (Kendall’s tau-b = 0.51). Average EMA-reported social support was uniquely associated with EMA-reported NSSI urges but not NSSI behaviors. Conclusions: EMA-reported perceived emotional social support captured information not represented by baseline reports alone, but improvement in model fit was modest. EMA-reported social support may further improve the estimation of EMA-reported NSSI urges if modeled as a proximal predictor of NSSI. Further work is needed to clarify temporal directions between social support and NSSI urges. Limitations are discussed

The Importance of Lassa Fever and Its Disease Management in West Africa

Lassa virus (LASV) is a zoonotic pathogen endemic throughout western Africa and is responsible for a human disease known as Lassa fever (LF). Historically, LASV has been emphasized as one of the greatest public health threats in West Africa, with up to 300,000 cases and 5000 associated deaths per year. This, and the fact that the disease has been reported in travelers, has driven a rapid production of various vaccine candidates. Several of these vaccines are currently in clinical development, despite limitations in understanding the immune response to infection. Alarmingly, the host immune response has been implicated in the induction of sensorineural hearing loss in LF survivors, legitimately raising safety questions about any future vaccines as well as efficacy in preventing potential hearing loss. The objective of this article is to revisit the importance and prevalence of LF in West Africa, with focus on Nigeria, and discuss current therapeutic approaches and ongoing vaccine development. In addition, we aim to emphasize the need for more scientific studies relating to LF-associated hearing loss, and to promote critical discussion about potential risks and benefits of vaccinating the population in endemic regions of West Africa

A bacterial extracellular vesicle-based intranasal vaccine against SARS-CoV-2 protects against disease and elicits neutralizing antibodies to wild-type and Delta variants

vaccines include mRNA-containing lipid nanoparticles or adenoviral vectors that encode the SARS-CoV-2 Several vaccines have been introduced to combat the coronavirus infectious disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current SARS-CoV-2 Spike (S) protein of SARS-CoV-2, inactivated virus, or protein subunits. Despite growing success in worldwide vaccination efforts, additional capabilities may be needed in the future to address issues such as stability and storage requirements, need for vaccine boosters, desirability of different routes of administration, and emergence of SARS-CoV-2 variants such as the Delta variant. Here, we present a novel, well-characterized SARS-CoV-2 vaccine candidate based on extracellular vesicles (EVs) of Salmonella typhimurium that are decorated with the mammalian cell culture-derived Spike receptor-binding domain (RBD). RBD-conjugated outer membrane vesicles (RBD-OMVs) were used to immunize the golden Syrian hamster (Mesocricetus auratus) model of COVID-19. Intranasal immunization resulted in high titers of blood anti-RBD IgG as well as detectable mucosal responses. Neutralizing antibody activity against wild-type and Delta variants was evident in all vaccinated subjects. Upon challenge with live virus, hamsters immunized with RBD-OMV, but not animals immunized with unconjugated OMVs or a vehicle control, avoided body mass loss, had lower virus titers in bronchoalveolar lavage fluid, and experienced less severe lung pathology. Our results emphasize the value and versatility of OMV-based vaccine approaches

A bacterial extracellular vesicle-based intranasal vaccine against SARS-CoV-2 protects against disease and elicits neutralizing antibodies to wild-type and Delta variants

Several vaccines have been introduced to combat the coronavirus infectious disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current SARS-CoV-2 vaccines include mRNA-containing lipid nanoparticles or adenoviral vectors that encode the SARS-CoV-2 Spike (S) protein of SARS-CoV-2, inactivated virus, or protein subunits. Despite growing success in worldwide vaccination efforts, additional capabilities may be needed in the future to address issues such as stability and storage requirements, need for vaccine boosters, desirability of different routes of administration, and emergence of SARS-CoV-2 variants such as the Delta variant. Here, we present a novel, well-characterized SARS-CoV-2 vaccine candidate based on extracellular vesicles (EVs) of Salmonella typhimurium that are decorated with the mammalian cell culture-derived Spike receptor-binding domain (RBD). RBD-conjugated outer membrane vesicles (RBD-OMVs) were used to immunize the golden Syrian hamster (Mesocricetus auratus) model of COVID-19. Intranasal immunization resulted in high titres of blood anti-RBD IgG as well as detectable mucosal responses. Neutralizing antibody activity against wild-type and Delta variants was evident in all vaccinated subjects. Upon challenge with live virus, hamsters immunized with RBD-OMV, but not animals immunized with unconjugated OMVs or a vehicle control, avoided body mass loss, had lower virus titres in bronchoalveolar lavage fluid, and experienced less severe lung pathology. Our results emphasize the value and versatility of OMV-based vaccine approaches