Vaccine-induced T cell responses control Orthoflavivirus challenge infection without neutralizing antibodies in humans.

T cells have been identified as correlates of protection in viral infections. However, the level of vaccine-induced T cells needed and the extent to which they alone can control acute viral infection in humans remain uncertain. Here we conducted a double-blind, randomized controlled trial involving vaccination and challenge in 33 adult human volunteers, using the live-attenuated yellow fever (YF17D) and chimeric Japanese encephalitis-YF17D (JE/YF17D) vaccines.

Dysregulated metabolism underpins Zika-virus-infection-associated impairment in fetal development.

Zika virus (ZIKV) is an Aedes-mosquito-borne flavivirus that causes debilitating congenital and developmental disorders. Improved understanding of ZIKV pathogenesis could assist efforts to fill the therapeutic and vaccine gap. We use several ZIKV strains, including a pair differing by a single phenylalanine-to-leucine substitution (M-F37L) in the membrane (M) protein, coupled with unbiased genomics to demarcate the border between attenuated and pathogenic infection.

The effects of aging on host resistance and disease tolerance to SARS-CoV-2 infection.

The ongoing coronavirus disease 2019 (COVID-19) crisis caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a large-scale pandemic that is afflicting millions of individuals in over 200 countries. The clinical spectrum caused by SARS-CoV-2 infections can range from asymptomatic infection to mild undifferentiated febrile illness to severe respiratory disease with multiple complications. Elderly patients (aged 60 and above) with comorbidities such as cardiovascular diseases and diabetes mellitus appear to be at highest risk of a severe disease outcome.

Antibody-Dependent Dengue Virus Entry Modulates Cell Intrinsic Responses for Enhanced Infection.

Dengue is caused by infection with any one of four dengue viruses (DENV); the risk of severe disease appears to be enhanced by the cross-reactive or subneutralizing levels of antibody from a prior DENV infection. These antibodies opsonize DENV entry through the activating Fc gamma receptors (FcγR), instead of infection through canonical receptor-mediated endocytosis, to result in higher levels of DENV replication. However, whether the enhanced replication is solely due to more efficient FcγR-mediated DENV entry or is also through FcγR-mediated alteration of the host transcriptome response to favor DENV infection remains unclear.

Metabolic perturbations and cellular stress underpin susceptibility to symptomatic live-attenuated yellow fever infection.

Flaviviral infections result in a wide spectrum of clinical outcomes, ranging from asymptomatic infection to severe disease. Although the correlates of severe disease have been explored, the pathophysiology that differentiates symptomatic from asymptomatic infection remains undefined. To understand the molecular underpinnings of symptomatic infection, the blood transcriptomic and metabolomic profiles of individuals were examined before and after inoculation with the live yellow fever viral vaccine (YF17D).

Dengue: an update on treatment options.

Dengue is the most important mosquito-borne viral pathogen globally, with approximately 100 million cases of acute dengue annually. Infection can result in severe, life-threatening disease. Currently, there is no effective vaccine or licensed antiviral.