Immunology of Infectious Disease News Volume 7.37 | Sep 25 2019

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FPR1 Is the Plague Receptor on Host Immune Cells

N-formylpeptide receptor (FPR1) was a plague receptor on immune cells in both humans and mice, and its absence or mutation provided protection against Yersinia pestis. [Nature] Abstract

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Germline-Encoded Affinity for Cognate Antigen Enables Vaccine Amplification of a Human Broadly Neutralizing Response against Influenza Virus

Scientists generated transgenic mice with human complementarity-determining region (CDRH3) diversity but simultaneously constrained to individual user-defined human immunoglobulin variable heavy-chain genes, including IGHV1-69, which showed biased usage in human bnAbs targeting the hemagglutinin stalk of group 1 influenza A viruses. Sequential immunization with a stalk-only hemagglutinin nanoparticle elicited group 1 bnAbs, but only in IGHV1-69 mice. [Immunity] Abstract | Graphical Abstract

Lrrk2 Alleles Modulate Inflammation during Microbial Infection of Mice in a Sex-Dependent Manner

In both mouse models, wild-type leucine-rich repeat kinase-2 (LRRK2) expression was protective and showed a sex effect, with female Lrrk2-deficient animals not controlling infection as well as males. Mice expressing Lrrk2 carrying the Parkinson’s disease-linked p.G2019S mutation controlled infection better, with reduced bacterial growth and longer animal survival during sepsis. [Sci Transl Med] Abstract

Immune Correlates of the Thai RV144 HIV Vaccine Regimen in South Africa

Investigators compared cellular and humoral responses at peak and durability immunogenicity time points in HIV Vaccine Trials Network 097 and RV144 vaccinee samples, and evaluated vaccine-matched and cross-clade immune responses. [Sci Transl Med] Full Article

Human Cytomegalovirus Overcomes SAMHD1 Restriction in Macrophages via pUL97

Human cytomegalovirus (HCMV) is a pathogenic virus with a tropism for non-dividing myeloid cells, in which sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1) is catalytically active. The authors investigated how HCMV achieved efficient propagation in these cells despite the SAMHD1-mediated dNTP depletion. [Nat Microbiol] Abstract

A Human Antithrombin Isoform Dampens Inflammatory Responses and Protects from Organ Damage during Bacterial Infection

Scientists demonstrated that in a lethal E. coli infection model, survival rates increased when mice were treated with less abundant β-isoform of human antithrombin one hour and five hours after infection. [Nat Microbiol] Abstract

Time Elapsed between Zika and Dengue Virus Infections Affects Antibody and T Cell Responses

Investigators showed that previous Zika virus (ZIKV) exposure increased the magnitude of the antibody and T cell responses against dengue virus (DENV). The time interval between ZIKV and subsequent DENV infection further affected the immune response [Nat Commun] Abstract

Potent Antibody Lineage against Malaria Transmission Elicited by Human Vaccination with Pfs25

Researchers present molecular analyses of human antibody responses generated in a clinical trial evaluating Pfs25 vaccination. From a collection of monoclonal antibodies with transmission-blocking activity, they identified the most potent transmission-blocking antibody yet described against Pfs25; 2544. [Nat Commun] Full Article

Colitis Susceptibility in Mice with Reactive Oxygen Species Deficiency Is Mediated by Mucus Barrier and Immune Defense Defects

The Cyba mutant mouse phenotype implicates loss of both mucus barrier and efficient innate immune defense in the pathogenesis of intestinal inflammation due to reactive oxygen species deficiency, supporting a combined-hit model where a single disease variant compromises different cellular functions in interdependent compartments. [Mucosal Immunol] Abstract

West Nile Virus Infection Blocks Inflammatory Response and T Cell Costimulatory Capacity of Human Monocyte-Derived Dendritic Cells

The authors demonstrated that human monocyte derived dendritic cells supported productive viral replication following infection with a pathogenic strain of West Nile virus. [J Virol] Abstract

The Human Papillomavirus (HPV) E1 Protein Regulates the Expression of Cellular Genes Involved in Immune Response

The authors found that E1 proteins from HPV16 and 18 induced an overexpression of different set of genes associated with proliferation and differentiation processes, as well as downregulation of immune response genes, including IFNβ1 and IFNλ1 and interferon-stimulated gene, which are important components involved in the antiviral immune response. [Sci Rep] Full Article

Nucleoside-Modified mRNA Encoding HSV-2 Glycoproteins C, D, and E Prevents Clinical and Subclinical Genital Herpes

Scientists evaluated a trivalent glycoprotein vaccine containing herpes simplex virus type 2 (HSV-2) entry molecule glycoprotein D and two immune evasion molecules: glycoprotein C, which binds complement C3b, and glycoprotein E, which blocks immunoglobulin G Fc activities [Sci Immunol] Full Article

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Restoring, Releasing or Replacing Adaptive Immunity in Chronic Hepatitis B

Investigators provide insight into key components of successful T cell and B cell responses to hepatitis B virus, discussing the importance of different specificities and effector functions, local intrahepatic immunity and pathogenic potential. [Nat Rev Gastroenterol Hepatol] Abstract

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Bavarian Nordic Announces US FDA Approval of JYNNEOS^™ (Smallpox and Monkeypox Vaccine, Live, Non-Replicating) for Prevention of Smallpox and Monkeypox Disease in Adults

Bavarian Nordic A/S announced that the FDA has approved JYNNEOS^™ for prevention of smallpox and monkeypox disease in adults 18 years of age and older determined to be at high risk for smallpox or monkeypox infection. [Bavarian Nordic A/S] Press Release

UEA Scientists Receive £7.4 Million Boost to Combat ‘Worst Superbugs’

University of East Anglia scientists are developing a new wave of drugs to combat antibiotic resistance – thanks to a £7.4 million ($9.2 million) boost. [University of East Anglia] Press Release

Inovio Receives NIH Funding to Target Its dMAb^® Technology against Antimicrobial-Resistant Infection

Inovio Pharmaceuticals, Inc. announced that the company and its collaborator The Wistar Institute have received a $4.6 million National Institutes of Health (NIH) grant in support of innovative research to tackle antimicrobial resistance employing Inovio’s DNA-encoded monoclonal antibodies (dMAb^®) platform. [Inovio Pharmaceuticals, Inc.] Press Release

Trump Signs Order to Improve Flu-Vaccine Development

The US government is launching a programme to modernize the development of flu vaccines. President Donald Trump signed an executive order on 19 September directing the Department of Health and Human Services and the Department of Defense to propose a plan and budget for the effort within 120 days. [Nature News] Editorial

Aid Group Says Ebola Vaccine Is Not Reaching Enough People

The aid organization Médecins Sans Frontiéres says that the World Health Organization is not distributing Ebola vaccine widely enough in the Democratic Republic of the Congo. [Nature News] Editorial

Can a New Lyme Disease Vaccine Overcome a History of Distrust and Failure?

As the threat of Lyme disease grows and fears surrounding it spread faster than the ticks that carry the infection, researchers are developing two vaccine or vaccine-like approaches to prevent this increasingly problematic disease. [STAT News] Editorial

NEW Cytokines 2019
October 20-23, 2019
Vienna, Austria

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NEW Postdoctoral Scientist – Flavivirus Infection (Pasteur Institute of Cambodia)

NEW Assistant/Associate Professor – Immunology (University of Massachusetts)

Research Associate – Immune Cell Culture (STEMCELL Technologies Inc.)

Faculty Position – Life Sciences (University of Michigan)

Staff Clinician – Malaria Immunology and Vaccinology (The National Institute of Allergy and Infectious Diseases)

Assistant Professor – Microbiology and Immunology (Stanford University School of Medicine)

Postdoctoral Fellowship – Respiratory Pathogens (Massachusetts General Hospital)

Senior Investigator and Laboratory Chief – Infectious Diseases (The National Institute of Allergy and Infectious Diseases)

Senior Scientist – Infectious Disease (The National Institute of Allergy and Infectious Diseases)

Director – Gladstone Institute of Virology and Immunology (Gladstone Institutes)

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