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Modified Vaccinia Ankara Vector-Based Vaccine Protects Macaques from SARS-CoV-2 Infection, Immune Pathology and Dysfunction in the Lung

ABSTRACT: Study show that modified vaccinia Ankara (MVA)-based COVID-19 vaccine expressing membrane anchored pre-fusion stabilized spike (MVA/S) induces both neutralizing antibodies and CD8+ T cells in the blood and lung and protects from SARS-CoV-2 challenge. Single-cell RNA sequencing analysis of lung cells at day 4 post-infection revealed that MVA/S vaccination also protected macaques from infection-induced inflammation and B cell abnormalities, and lowered induction of interferon stimulated genes.

ORGANISM(S): Macaca mulatta

PROVIDER: GSE165747 | GEO | 2021/02/01

REPOSITORIES: GEO

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Quantitative temporal proteomic analysis of modified vaccinia Ankara, a mpox vaccine

Project description:Modified vaccinia Ankara (MVA) immunisation is being deployed to curb the current outbreak of mpox in multiple countries1. Originally authorized for vaccination against smallpox, MVA is a vaccinia virus (VACV) strain that does not replicate in human cells or cause serious adverse events. Here, we conducted a highly multiplexed proteomic analysis2 to quantify >9,000 cellular proteins and ~80% of viral proteins at five time points throughout MVA infection of human cells3. 690 human proteins were down-regulated >2-fold by MVA, revealing a substantial remodelling of the host proteome. >25% of these MVA targets, including multiple components of the nuclear pore complex (NPC), were not shared with VACV-Western Reserve4, which is derived from a first generation smallpox vaccine associated with serious adverse events. Using pharmacological inhibition of viral DNA replication and heat-inactivated virions, we discovered that post-replicative gene expression is necessary for the downregulation of NPC proteins and for elements of MVA antagonism of innate immune sensing. Our approach thus provides the first global view of the impact of MVA infection on the host proteome, offers insights into how MVA interacts with the antiviral defences and identifies cellular mechanisms that may underpin the abortive infection of human cells. These discoveries will prove vital to the rational design of future generations of vaccines.

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Modified Vaccinia Ankara Vector-Based Vaccine Protects Macaques from SARS-CoV-2 Infection, Immune Pathology and Dysfunction in the Lung

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