Respiratory syncytial virus infection provides protection against severe acute respiratory syndrome coronavirus challenge.

Unlabelled: Respiratory infections are a major health burden worldwide. Respiratory syncytial virus (RSV) is among the leading causes of hospitalization in both young children and older adults. The onset of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and the public health response had a profound impact on the normal seasonal outbreaks of other respiratory viruses.

Fusing safety and efficacy: A maternal bivalent RSV prefusion F vaccine.

In this phase 3 trial, Kampmann et al. demonstrated safety and efficacy of a maternal bivalent RSV prefusion F vaccine. Vaccine efficacy was achieved in reducing severe RSV-associated lower respiratory tract infections in infants at 90 and 180 days following birth.

Cutting Edge: Influenza-Induced CD11alo Airway CD103+ Tissue Resident Memory T Cells Exhibit Compromised IFN-γ Production after In Vivo TCR Stimulation.

Although tissue resident memory T cells (TRM) in the lung confer robust protection against secondary influenza infection, their in vivo production of IFN-γ is unknown. In this study, using a mouse model, we evaluated production of IFN-γ by influenza-induced TRM (defined as CD103+) that localize to the airways or lung parenchyma. Airway TRM consist of both CD11ahi and CD11alo populations, with low CD11a expression signifying prolonged airway residence.

Topical Adenosine Inhibits Inflammation and Mucus Production in Viral Acute Rhinosinusitis.

Objective: Viral acute rhinosinusitis (ARS) is the leading cause of work and school absence and antibiotic over-prescription. There are limited treatment options available to ameliorate the symptoms caused by viral ARS. We have previously demonstrated that topical adenosine treatment enhances mucociliary clearance in the sino-nasal tract.

Long-Lasting Protection Induced by a Polyanhydride Nanovaccine against Respiratory Syncytial Virus in an Outbred Mouse Model.

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in children. In humans, natural infection with RSV affords only partial long-term protection from reinfection, and there is no licensed RSV vaccine currently available. We have developed a new vaccine candidate, termed RSVNanoVax, composed of polyanhydride nanoparticles encapsulating the RSV prefusion F protein and a CpG 1668 oligodeoxynucleotide adjuvant.

A live single-cycle RSV vaccine expressing prefusion F protein.

Live-attenuated Respiratory syncytial virus (RSV) vaccines given intranasally have potential to provide comprehensive protection, including lung-resident immunity. It has however proven challenging to impart both sufficient safety and efficacy in a vaccine. To achieve the latter, we used a trans-complementing approach to generate live single-cycle RSV vaccines expressing the prefusion form (preF) of the viral fusion protein (F), either membrane-anchored or secreted.

Use of compressed sensing to expedite high-throughput diagnostic testing for COVID-19 and beyond.

The rapid spread of SARS-CoV-2 has placed a significant burden on public health systems to provide swift and accurate diagnostic testing highlighting the critical need for innovative testing approaches for future pandemics. In this study, we present a novel sample pooling procedure based on compressed sensing theory to accurately identify virally infected patients at high prevalence rates utilizing an innovative viral RNA extraction process to minimize sample dilution. At prevalence rates ranging from 0-14.

Influenza-Induced CD103 T Resident Memory Cells Exhibit Enhanced Functional Avidity over CD103 Memory T Cells in the Mediastinal Lymph Node.

Influenza virus-specific tissue-resident memory CD8 T cells (Trms) targeting conserved viral proteins provide strain-transcending heterosubtypic immunity to infection. Trms in the lung combat reinfection through rapid cytolytic function and production of inflammatory cytokines to recruit other immune cells. Influenza-specific Trms are also generated in the lung draining mediastinal lymph node (mLN) and can provide immunity to heterologous virus infection in this tissue, although their role in combating influenza infection is less well defined.

Pharmacological ascorbate as a novel therapeutic strategy to enhance cancer immunotherapy.

Pharmacological ascorbate (i.e., intravenous infusions of vitamin C reaching ~ 20 mM in plasma) is under active investigation as an adjuvant to standard of care anti-cancer treatments due to its dual redox roles as an antioxidant in normal tissues and as a prooxidant in malignant tissues.

Pharmacological ascorbate improves the response to platinum-based chemotherapy in advanced stage non-small cell lung cancer.

Purpose: Platinum-based chemotherapy with or without immunotherapy is the mainstay of treatment for advanced stage non-small cell lung cancer (NSCLC) lacking a molecular driver alteration. Pre-clinical studies have reported that pharmacological ascorbate (P-AscH-) enhances NSCLC response to platinum-based therapy. We conducted a phase II clinical trial combining P-AscH- with carboplatin-paclitaxel chemotherapy.

Respiratory Syncytial Virus Provides Protection against a Subsequent Influenza A Virus Infection.

Respiratory infections are a leading cause of morbidity and mortality. The presence of multiple heterologous virus infections is routinely observed in a subset of individuals screened for the presence of respiratory viruses. However, the impact overlapping infections has on disease severity and the host immune response is not well understood.

Use of compressed sensing to expedite high-throughput diagnostic testing for COVID-19 and beyond.

The rapid spread of SARS-CoV-2 has placed a significant burden on public health systems to provide rapid and accurate diagnostic testing highlighting the critical need for innovative testing approaches for future pandemics. In this study, we present a novel sample pooling procedure based on compressed sensing theory to accurately identify virally infected patients at high prevalence rates utilizing an innovative viral RNA extraction process to minimize sample dilution. At prevalence rates ranging from 0-14.

American Association of Immunologists Recommendations for an Undergraduate Course in Immunology.

Identifying the "essential" components of an undergraduate immunology lecture course can be daunting because of the varying postgraduate pathways students take. The American Association of Immunologists Education Committee commissioned an Ad Hoc Committee, representing undergraduate, graduate, and medical institutions as well as the biotechnology community, to develop core curricular recommendations for teaching immunology to undergraduates. In a reiterative process involving the American Association of Immunologists teaching community, 14 key topics were identified and expanded to include foundational concepts, subtopics and examples, and advanced subtopics, providing a flexible list for curriculum development and avenues for higher-level learning.

Intratumoral talimogene laherparepvec injection with concurrent preoperative radiation in patients with locally advanced soft-tissue sarcoma of the trunk and extremities: phase IB/II trial.

Background: Soft-tissue sarcomas (STS) in the extremities and trunk treated with standard-of-care preoperative external beam radiation therapy (EBRT) followed by surgical resection are associated with local and distant relapses. In preclinical studies, oncolytic virotherapy in sarcoma has demonstrated antitumor effects via direct intratumoral oncolysis and cytotoxic T-cell-mediated immune responses. Talimogene laherparepvec (TVEC) is a replication-competent, immune-enhanced, oncolytic herpes simplex virus type 1 engineered for intratumoral injection; it has been approved by the FDA for the treatment of locally advanced and metastatic melanoma.

Considerations for a Respiratory Syncytial Virus Vaccine Targeting an Elderly Population.

Respiratory syncytial virus (RSV) is most commonly associated with acute lower respiratory tract infections in infants and children. However, RSV also causes a high disease burden in the elderly that is often under recognized. Adults >65 years of age account for an estimated 80,000 RSV-associated hospitalizations and 14,000 deaths in the United States annually.

Protective function and durability of mouse lymph node-resident memory CD8 T cells.

Protective lung tissue-resident memory CD8T cells (Trm) form after influenza A virus (IAV) infection. We show that IAV infection of mice generates CD69CD103and other memory CD8T cell populations in lung-draining mediastinal lymph nodes (mLNs) from circulating naive or memory CD8T cells. Repeated antigen exposure, mimicking seasonal IAV infections, generates quaternary memory (4M) CD8T cells that protect mLN from viral infection better than 1M CD8T cells.

Prefusion F-Based Polyanhydride Nanovaccine Induces Both Humoral and Cell-Mediated Immunity Resulting in Long-Lasting Protection against Respiratory Syncytial Virus.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection in both young children and in older adults. Despite the morbidity, mortality, and high economic burden caused by RSV worldwide, no licensed vaccine is currently available. We have developed a novel RSV vaccine composed of a prefusion-stabilized variant of the fusion (F) protein (DS-Cav1) and a CpG oligodeoxynucleotide adjuvant encapsulated within polyanhydride nanoparticles, termed RSVNanoVax.

Tissue-Resident Memory T Cells in the Lungs Protect against Acute Respiratory Syncytial Virus Infection.

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in young children. The T cell response plays a critical role in facilitating clearance of an acute RSV infection, and memory T cell responses are vital for protection against secondary RSV exposures. Tissue-resident memory (TRM) T cells have been identified as a subset of memory T cells that reside in nonlymphoid tissues and are critical for providing long-term immunity.

Nanoparticle vaccines against respiratory syncytial virus.

Respiratory syncytial virus (RSV) is a leading cause of respiratory disease in infants, the elderly and immunocompromised individuals. Despite the global burden, there is no licensed vaccine for RSV. Recent advances in the use of nanoparticle technology have provided new opportunities to address some of the limitations of conventional vaccines.

Function and Modulation of Type I Interferons during Respiratory Syncytial Virus Infection.

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory infections in infants and young children, accounting for an estimated 3 million hospitalizations annually worldwide. Despite the major health burden, there is currently no licensed RSV vaccine. RSV is recognized by a range of cellular receptors including both toll-like receptors (TLR) and retinoic acid-inducible gene-I-like receptors (RIG-I).

Pre-existing neutralizing antibodies prevent CD8 T cell-mediated immunopathology following respiratory syncytial virus infection.

Despite being a leading cause of severe respiratory disease, there remains no licensed respiratory syncytial virus (RSV) vaccine. Neutralizing antibodies reduce the severity of RSV-associated disease, but are not sufficient for preventing reinfection. In contrast, the role of memory CD8 T cells in protecting against a secondary RSV infection is less established.

Identification of Novel Respiratory Syncytial Virus CD4 and CD8 T Cell Epitopes in C57BL/6 Mice.

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection and hospitalization in infants. It is well established that both CD4 and CD8 T cells are critical for mediating viral clearance but also contribute to the induction of immunopathology following RSV infection. C57BL/6 mice are often used to study T cell responses following RSV infection given the wide variety of genetically modified animals available.

Airway Surface Liquid Has Innate Antiviral Activity That Is Reduced in Cystic Fibrosis.

Although chronic bacterial infections and inflammation are associated with progressive lung disease in patients with cystic fibrosis (CF), much less is known regarding the contributions of respiratory viral infections to this process. Clinical studies suggest that antiviral host defenses may be compromised in individuals with CF, and CF airway epithelia exhibit impaired antiviral responses . Here, we used the CF pig model to test the hypothesis that the antiviral activity of respiratory secretions is reduced in CF.