Viral Vector-Based Vaccines Encoding CTH522 Induce Distinct Immune Responses in C57BL/6J and HLA Transgenic Mice.

remains a major global health problem with increasing infection rates, requiring innovative vaccine solutions. Modified Vaccinia Virus Ankara (MVA) is a well-established, safe and highly immunogenic vaccine vector, making it a promising candidate for vaccine development. In this study, we evaluated two novel MVA-based recombinant vaccines expressing spCTH522 and CTH522:B7 antigens.

The purinergic receptor P2X7 as a modulator of viral vector-mediated antigen cross-presentation.

Introduction: Modified Vaccinia Virus Ankara (MVA) is a safe vaccine vector inducing long- lasting and potent immune responses. MVA-mediated CD8T cell responses are optimally induced, if both, direct- and cross-presentation of viral or recombinant antigens by dendritic cells are contributing.

Methods: To improve the adaptive immune responses, we investigated the role of the purinergic receptor P2X7 (P2RX7) in MVA-infected feeder cells as a modulator of cross-presentation by non-infected dendritic cells.

Regulation of STING activity in DNA sensing by ISG15 modification.

Sensing of human immunodeficiency virus type 1 (HIV-1) DNA is mediated by the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling axis. Signal transduction and regulation of this cascade is achieved by post-translational modifications. Here we show that cGAS-STING-dependent HIV-1 sensing requires interferon-stimulated gene 15 (ISG15).

Odynophagia as the first symptom of monkeypox infection.

A 50-year-old patient with confirmed monkeypox infection presented with odynophagia and nocturnal dyspnea. Clinically, there was a lesion on the tongue without any skin lesions and fibrinous plaques on the right tonsil with asymmetry of the palatoglossal arch. Due to a suggested abscess in the CT scan, a tonsillectomy à chaud was performed.

Stability and Inactivation of Monkeypox Virus on Inanimate Surfaces.

The spread of nonzoonotic monkeypox virus (MPXV) infections necessitates the reevaluation of hygiene measures. To date, only limited data are available on MPXV surface stability. Here, we evaluate the stability of infectious MPXV on stainless steel stored at different temperatures, while using different interfering substances to mimic environmental contamination.

[Odynophagia as the first symptom of monkeypox infection].

A 50-year-old patient with confirmed monkeypox infection presented with odynophagia and nocturnal dyspnea. Clinically, there was a lesion on the tongue without any skin lesions and fibrinous plaques on the right tonsil with asymmetry of the palatoglossal arch. Due to a suggested abscess in the CT scan, a tonsillectomy à chaud was performed.

Efficient Inactivation of Monkeypox Virus by World Health Organization‒Recommended Hand Rub Formulations and Alcohols.

Increasing nonzoonotic human monkeypox virus (MPXV) infections urge reevaluation of inactivation strategies. We demonstrate efficient inactivation of MPXV by 2 World Health Organization‒recommended alcohol-based hand rub solutions. When compared with other (re)emerging enveloped viruses, MPXV displayed the greatest stability.

Adjusted COVID-19 booster schedules balance age-dependent differences in antibody titers benefitting risk populations.

We provide follow-up data on the humoral immune response after COVID-19 vaccinations of two distinct cohorts aged below 60 and over 80 years to screen for age-related differences in the longevity and magnitude of the induction of the antibody responses post booster-vaccinations. While anti-SARS-CoV-2 spike-specific IgG and neutralization capacity waned rapidly after the initial vaccination schedule, additional boosters highly benefitted the humoral immune responses especially in the elderly cohort, including the neutralization of Omikron variants. Thus, adjusted COVID-19 booster vaccination schedules are an appropriate tool to overcome limitations in the success of vaccinations.

Vaccinia Virus: From Crude Smallpox Vaccines to Elaborate Viral Vector Vaccine Design.

Various vaccinia virus (VACV) strains were applied during the smallpox vaccination campaign to eradicate the variola virus worldwide. After the eradication of smallpox, VACV gained popularity as a viral vector thanks to increasing innovations in genetic engineering and vaccine technology. Some VACV strains have been extensively used to develop vaccine candidates against various diseases.

SARS-CoV-2 Infection in Fully Vaccinated Individuals of Old Age Strongly Boosts the Humoral Immune Response.

Prophylactic vaccination against SARS-CoV-2 is one of the most important measures to contain the COVID-19 pandemic. Recently, break-through infections following vaccination against this virus have been reported. Here, we describe the humoral immune response of break-through infections in fully vaccinated individuals of old age from an outbreak in a nursing home.

A conceptual approach to the rationale for SARS-CoV-2 vaccine allocation prioritisation.

Currently vaccines protecting from COVID-19 are a scarce resource. Prioritising vaccination for certain groups of society is placed in a context of uncertainty due to changing evidence on the available vaccines and changing infection dynamics. To meet accepted ethical standards of procedural justice and individual autonomy, vaccine allocation strategies need to state reasons for prioritisation explicitly while at the same time communicating the expected risks and benefits of vaccination at different times and with different vaccines transparently.

Age-dependent Immune Response to the Biontech/Pfizer BNT162b2 Coronavirus Disease 2019 Vaccination.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has led to the development of various vaccines. Real-life data on immune responses elicited in the most vulnerable group of vaccinees older than age 80 years old are still underrepresented despite the prioritization of the elderly in vaccination campaigns.

Methods: We conducted a cohort study with 2 age groups, young vaccinees below the age of 60 years and elderly vaccinees over the age of 80 years, to compare their antibody responses to the first and second dose of the BNT162b2 coronavirus disease 2019 vaccination.

Sensitivity of anti-SARS-CoV-2 serological assays in a high-prevalence setting.

Evaluation and power of seroprevalence studies depend on the performed serological assays. The aim of this study was to assess four commercial serological tests from EUROIMMUN, DiaSorin, Abbott, and Roche as well as an in-house immunofluorescence and neutralization test for their capability to identify SARS-CoV-2 seropositive individuals in a high-prevalence setting. Therefore, 42 social and working contacts of a German super-spreader were tested.

A Broad-Spectrum Antiviral Peptide Blocks Infection of Viruses by Binding to Phosphatidylserine in the Viral Envelope.

The ongoing threat of viral infections and the emergence of antiviral drug resistance warrants a ceaseless search for new antiviral compounds. Broadly-inhibiting compounds that act on elements shared by many viruses are promising antiviral candidates. Here, we identify a peptide derived from the cowpox virus protein CPXV012 as a broad-spectrum antiviral peptide.

Efficient Induction of Cytotoxic T Cells by Viral Vector Vaccination Requires STING-Dependent DC Functions.

Modified Vaccinia virus Ankara (MVA) is an attenuated strain of vaccinia virus and currently under investigation as a promising vaccine vector against infectious diseases and cancer. MVA acquired mutations in host range and immunomodulatory genes, rendering the virus deficient for replication in most mammalian cells. MVA has a high safety profile and induces robust immune responses.

Targeting Autophagy in Innate Immune Cells: Angel or Demon During Infection and Vaccination?

Innate immune cells are the "doorkeepers" in the immune system and are important for the initiation of protective vaccine responses against infection. Being an essential regulatory component of the immune system in these cells, autophagy not only mediates pathogen clearance and cytokine production, but also balances the immune response by preventing harmful overreaction. Interestingly, recent literature indicates that autophagy is positively or negatively regulating the innate immune response in a cell type-specific manner.

ORF6 and ORF61 Expressing MVA Vaccines Impair Early but Not Late Latency in Murine Gammaherpesvirus MHV-68 Infection.

Gammaherpesviruses (γHV) are important pathogens causing persistent infections which lead to several malignancies in immunocompromised patients. Murine γHV 68 (MHV-68), a homolog to human EBV and KSHV, has been employed as a classical pathogen to investigate the molecular pathogenicity of γHV infections. γHV express distinct antigens during lytic or latent infection and antigen-specific T cells have a significant role in controlling the acute and latent viral infection, although the quality of anti-viral T cell responses required for protective immunity is not well-understood.

Sequestration of Late Antigens Within Viral Factories Impairs MVA Vector-Induced Protective Memory CTL Responses.

Cytotoxic CD8+ T cell (CTL) responses play an essential role in antiviral immunity. Here, we focused on the activation of CTL which recognize epitopes derived from viral or recombinant antigens with either early or late expression kinetics after infection with Modified Vaccinia Virus Ankara (MVA). Late antigens but not early antigens failed to efficiently stimulate murine CTL lines and were unable to activate and expand protective memory T cell responses in mice .

Diverse Immunomodulatory Effects of Individual IFNα Subtypes on Virus-Specific CD8 T Cell Responses.

Clinical administration of Interferon α (IFNα) resulted in limited therapeutic success against some viral infections. Immune modulation of CD8 T cell responses during IFNα therapy is believed to play a pivotal role in promoting viral clearance. However, these clinical studies primarily focused on IFNα subtype 2.

Generation of recombinant MVA-norovirus: a comparison study of bacterial artificial chromosome- and marker-based systems.

Background: Recombinant Modified Vaccinia Virus Ankara has been employed as a safe and potent viral vector vaccine against infectious diseases and cancer. We generated recMVAs encoding norovirus GII.4 genotype capsid protein by using a marker-based approach and a BAC-based system.

Modified Vaccinia Virus Ankara Can Induce Optimal CD8 T Cell Responses to Directly Primed Antigens Depending on Vaccine Design.

A variety of strains of vaccinia virus (VACV) have been used as recombinant vaccine vectors with the aim of inducing robust CD8 T cell immunity. While much of the pioneering work was done with virulent strains, such as Western Reserve (WR), attenuated strains such as modified vaccinia virus Ankara (MVA) are more realistic vectors for clinical use. To unify this literature, side-by-side comparisons of virus strains are required.

A Genome-Wide Haploid Genetic Screen Identifies Heparan Sulfate-Associated Genes and the Macropinocytosis Modulator TMED10 as Factors Supporting Vaccinia Virus Infection.

Vaccinia virus is a promising viral vaccine and gene delivery candidate and has historically been used as a model to study poxvirus-host cell interactions. We employed a genome-wide insertional mutagenesis approach in human haploid cells to identify host factors crucial for vaccinia virus infection. A library of mutagenized HAP1 cells was exposed to modified vaccinia virus Ankara (MVA).

Corrigendum: Interleukin-2-Inducible T-Cell Kinase Deficiency-New Patients, New Insight?

[This corrects the article DOI: 10.3389/fimmu.2018.

Impact of the TAP-like transporter in antigen presentation and phagosome maturation.

Cross-presentation is thought to require transport of proteasome-generated peptides by the TAP transporters into MHC class I loading compartments for most antigens. However, a proteasome-dependent but TAP-independent pathway has also been described. Depletion of the pool of recycling cell surface MHC class I molecules available for loading with cross-presented peptides might partly or largely account for the critical role of TAP in cross-presentation of phagocytosed antigens.

Interleukin-2-Inducible T-Cell Kinase Deficiency-New Patients, New Insight?

Patients with primary immunodeficiency can be prone to severe Epstein-Barr virus (EBV) associated immune dysregulation. Individuals with mutations in the interleukin-2-inducible T-cell kinase () gene experience Hodgkin and non-Hodgkin lymphoma, EBV lymphoproliferative disease, hemophagocytic lymphohistiocytosis, and dysgammaglobulinemia. In this review, we give an update on further reported patients.