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

PROVIDER: PRJNA695575 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13575000_1.fastq.gz	Fastqsanger.gz
	SRR13575000_2.fastq.gz	Fastqsanger.gz
	SRR13575001_1.fastq.gz	Fastqsanger.gz
	SRR13575001_2.fastq.gz	Fastqsanger.gz
	SRR13575002_1.fastq.gz	Fastqsanger.gz

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

Project description: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.

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Bulk RNA sequencing study of female rhesus macaques given Modified versions of the RhCMV/SIV vector-based vaccines.

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Modified Vaccinia virus Ankara vector induces specific cellular and humoral responses in the female reproductive tract, the main HIV portal of entry

Project description:The female reproductive tract is one of the major mucosal invasion site of HIV-1. This site has been neglected in previous HIV-1 vaccine studies. Immune responses in the female reproductive tract after systemic vaccination remain to be characterized. Using a modified vaccinia virus Ankara (MVA) as a vaccine model, we characterized specific immune responses in all compartments of the female reproductive tract (FRT) of non-human primates after systemic vaccination. Memory T cells were preferentially found in the lower tract (vagina and cervix), whereas antigen-presenting cells and innate lymphoid cells were mainly located in the upper tract (uterus and fallopian tubes). This compartmentalisation of immune cells in the FRT was supported by transcriptomic analyses and correlation network. Polyfunctional MVA-specific CD8+ T cells were detected in the blood, lymph nodes, vagina, cervix, uterus and fallopian tubes. Anti-MVA IgG and IgA were detected in cervicovaginal fluid after a second vaccine dose. Systemic vaccination with an MVA vector thus elicits cellular and antibody responses in the female reproductive tract.

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Bulk RNA sequencing study of Rhesus macaques given Modified versions of the RhCMV/SIV vector-based vaccines.

Project description:Bulk RNA sequencing study of Rhesus macaques given Modified versions of the RhCMV/SIV vector-based vaccines.

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Project description:Bulk RNA sequencing study of female rhesus macaques given Modified versions of the RhCMV/SIV vector-based vaccines.

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A modified vaccinia Ankara vector-based vaccine protects macaques from SARS-CoV-2 infection, immune pathology, and dysfunction in the lungs.

Project description:A combination of vaccination approaches will likely be necessary to fully control the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Here, we show that modified vaccinia Ankara (MVA) vectors expressing membrane-anchored pre-fusion stabilized spike (MVA/S) but not secreted S1 induced strong neutralizing antibody responses against SARS-CoV-2 in mice. In macaques, the MVA/S vaccination induced strong neutralizing antibodies and CD8+ T cell responses, and conferred protection from SARS-CoV-2 infection and virus replication in the lungs as early as day 2 following intranasal and intratracheal challenge. Single-cell RNA sequencing analysis of lung cells on day 4 after infection revealed that MVA/S vaccination also protected macaques from infection-induced inflammation and B cell abnormalities and lowered induction of interferon-stimulated genes. These results demonstrate that MVA/S vaccination induces neutralizing antibodies and CD8+ T cells in the blood and lungs and is a potential vaccine candidate for SARS-CoV-2.

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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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A modified vaccinia Ankara vaccine vector expressing a mosaic H5 hemagglutinin reduces viral shedding in rhesus macaques.

Project description:The rapid antigenic evolution of influenza viruses requires frequent vaccine reformulations. Due to the economic burden of continuous vaccine reformulation and the threat of new pandemics, there is intense interest in developing vaccines capable of eliciting broadly cross-reactive immunity to influenza viruses. We recently constructed a "mosaic" hemagglutinin (HA) based on subtype 5 HA (H5) and designed to stimulate cellular and humoral immunity to multiple influenza virus subtypes. Modified vaccinia Ankara (MVA) expressing this H5 mosaic (MVA-H5M) protected mice against multiple homosubtypic H5N1 strains and a heterosubtypic H1N1 virus. To assess its potential as a human vaccine we evaluated the ability of MVA-H5M to provide heterosubtypic immunity to influenza viruses in a non-human primate model. Rhesus macaques received an initial dose of either MVA-H5M or plasmid DNA encoding H5M, followed by a boost of MVA-H5M, and then were challenged, together with naïve controls, with the heterosubtypic virus A/California/04/2009 (H1N1pdm). Macaques receiving either vaccine regimen cleared H1N1pdm challenge faster than naïve controls. Vaccination with H5M elicited antibodies that bound H1N1pdm HA, but did not neutralize the H1N1pdm challenge virus. Plasma from vaccinated macaques activated NK cells in the presence of H1N1pdm HA, suggesting that vaccination elicited cross-reactive antibodies capable of mediating antibody-dependent cell-mediated cytotoxicity (ADCC). Although HA-specific T cell responses to the MVA-H5M vaccine were weak, responses after challenge were stronger in vaccinated macaques than in control animals. Together these data suggest that mosaic HA antigens may provide a means for inducing broadly cross-reactive immunity to influenza viruses.

| S-EPMC5542451 | biostudies-literature

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