Harnessing the immune system to overcome cytokine storm and reduce viral load in COVID-19: a review of the phases of illness and therapeutic agents.

Background: Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, previously named 2019-nCov), a novel coronavirus that emerged in China in December 2019 and was declared a global pandemic by World Health Organization by March 11th, 2020. Severe manifestations of COVID-19 are caused by a combination of direct tissue injury by viral replication and associated cytokine storm resulting in progressive organ damage.

Discussion: We reviewed published literature between January 1st, 2000 and June 30th, 2020, excluding articles focusing on pediatric or obstetric population, with a focus on virus-host interactions and immunological mechanisms responsible for virus associated cytokine release syndrome (CRS).

Characterization of a live-attenuated HCMV-based vaccine platform.

Vaccines based on cytomegalovirus (CMV) demonstrate protection in animal models of infectious disease and cancer. Vaccine efficacy is associated with the ability of CMV to elicit and indefinitely maintain high frequencies of circulating effector memory T cells (T) providing continuous, life-long anti-pathogen immune activity. To allow for the clinical testing of human CMV (HCMV)-based vaccines we constructed and characterized as a vector backbone the recombinant molecular clone TR3 representing a wildtype genome.

Demarcated thresholds of tumor-specific CD8 T cells elicited by MCMV-based vaccine vectors provide robust correlates of protection.

Background: The capacity of cytomegalovirus (CMV) to elicit long-lasting strong T cell responses, and the ability to engineer the genome of this DNA virus positions CMV-based vaccine vectors highly suitable as a cancer vaccine platform. Defined immune thresholds for tumor protection and the factors affecting such thresholds have not well been investigated in cancer immunotherapy. We here determined using CMV as a vaccine platform whether critical thresholds of vaccine-specific T cell responses can be established that relate to tumor protection, and which factors control such thresholds.

Intracranial Abscess and Post-Infectious Vasculitis.

Intracranial abscesses are rare complications of infections, and to our knowledge, there have been no case reports of post-infectious vasculitis developing in such patients. Here we describe the case of a 48-year-old post-splenectomy male who developed post-infectious vasculitis following otitis media complicated by mastoiditis, osteomyelitis, meningitis, and intracranial abscess. Clinicians ought to be aware of the possible adverse outcomes of invasive and the limitations of current treatment options.

Peptide Processing Is Critical for T-Cell Memory Inflation and May Be Optimized to Improve Immune Protection by CMV-Based Vaccine Vectors.

Cytomegalovirus (CMV) elicits long-term T-cell immunity of unparalleled strength, which has allowed the development of highly protective CMV-based vaccine vectors. Counterintuitively, experimental vaccines encoding a single MHC-I restricted epitope offered better immune protection than those expressing entire proteins, including the same epitope. To clarify this conundrum, we generated recombinant murine CMVs (MCMVs) encoding well-characterized MHC-I epitopes at different positions within viral genes and observed strong immune responses and protection against viruses and tumor growth when the epitopes were expressed at the protein C-terminus.