Immunology of Infectious Disease News Volume 3.14 | Apr 15 2015

Novel Chimpanzee Adenovirus-Vectored Respiratory Mucosal Tuberculosis Vaccine: Overcoming Local Anti-Human Adenovirus Immunity for Potent TB Protection
Scientists developed a novel chimpanzee adenovirus 68 (AdCh68)-vectored tuberculosis (TB) vaccine amenable to the respiratory route of vaccination. They evaluated AdCh68-based TB vaccine for its safety, T-cell immunogenicity, and protective efficacy in relevant animal models of human pulmonary TB with or without parenteral Bacillus Calmette-Guérin priming. [Mucosal Immunol] Abstract

Immunization with Ty21a Live Oral Typhoid Vaccine Elicits Crossreactive Multifunctional CD8⁺ T-Cell Responses against Salmonella enterica Serovar Typhi, S. Paratyphi A, and S. Paratyphi B in Humans
Researchers measured Salmonella-specific multifunctional CD8⁺ T-cell responses to investigate whether Ty21a elicits crossreactive cell-mediated immune responses against S. Paratyphi A and S. Paratyphi B that also cause enteric fever. [Mucosal Immunol] Abstract

Impaired NK Cell Responses to Pertussis and H1N1 Influenza Vaccine Antigens in Human Cytomegalovirus-Infected Individuals
In a cross-sectional study of 152 U.K. adults, with human cytomegalovirus (HCMV) seroprevalence rate of 36%, investigators found that HCMV seropositivity is associated with lower NK cell IFN-γ production and degranulation after in vitro restimulation with pertussis or H1N1 influenza vaccine Ags. [J Immunol]
Abstract | Full Article

HIV

Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection
Researchers characterized the rate of maturation and extent of diversity for the lineage that produced the broadly neutralizing antibody VRC01 through longitudinal sampling of peripheral B cell transcripts over 15 years and co-crystal structures of lineage members. [Cell] Abstract | Graphical Abstract

Analysis of Immunoglobulin Transcripts and Hypermutation following SHIV_AD8 Infection and Protein-Plus-Adjuvant Immunization
Scientists used two nonhuman primate models to compare the roles of antigen persistence, diversity and innate immunity. They performed longitudinal analyses of HIV Envelope (Env)-specific B-cell receptor responses to SHIV_AD8 infection and Env protein vaccination with eight different adjuvants. [Nat Commun] Full Article

Identification of Preferential CD4⁺ T-Cell Targets for HIV Infection in the Cervix
Investigators used a CCR5-tropic pseudovirus to quantify HIV entry into unstimulated endocervical CD4⁺ T cells collected by cytobrush. Virus entry was threefold higher into cervix-derived CD4⁺ T cells than blood, but was strongly correlated between these two compartments. [Mucosal Immunol] Abstract

Comparison of Immunogenicity in Rhesus Macaques of Transmitted-Founder, HIV-1 Group M Consensus and Trivalent Mosaic Envelope Vaccines Formulated as a DNA Prime, NYVAC and Envelope Protein Boost
Researchers compared the immunogenicity of a transmitted-founder B clade Env, a global group M consensus Env, and a global trivalent mosaic Env protein in rhesus macaques. These antigens were delivered using a DNA prime-rNYVAC vector and Env protein boost vaccination strategy. [J Virol] Abstract

Heterologous Prime-Boost Regimens with a Recombinant Chimpanzee Adenoviral Vector and Adjuvanted F4 Protein Elicit Polyfunctional HIV-1-Specific T-Cell Responses in Macaques
Researchers evaluated the immunogenicity of AdC7-GRN, a recombinant chimpanzee adenovirus type 7 vector expressing clade B Gag, RT and Nef, and F4/AS01, when delivered intramuscularly in homologous and heterologous prime-boost regimens, in macaques and mice. Vaccine-induced HIV-1-antigen-specific T cells in peripheral blood, liver, spleen, and intestinal and genital mucosa were characterized by intracellular cytokine staining. [PLoS One] Full Article

Engineering Cellular Resistance to HIV-1 Infection In Vivo Using a Dual Therapeutic Lentiviral Vector
Investigators utilized a humanized bone marrow, liver, thymus mouse model to characterize the in vivo efficacy of LVsh5/C46 (Cal-1) vector to engineer cellular resistance to HIV-1 pathogenesis. Splenocytes isolated from the treatment group were resistant to both R5- and X4-tropic HIV-1 during ex vivo challenge experiments. [Mol Ther Nucleic Acids] Full Article

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Ichor Medical Systems Announces Strategic Collaboration with Johnson & Johnson Innovation to Develop and Commercialize Immunotherapies Delivered with TriGrid Electroporation Device for Chronic Hepatitis B
Ichor Medical Systems, Inc. announced that it has entered into a product development collaboration and worldwide license agreement with Janssen Pharmaceuticals, Inc. Under the agreement, the parties will work together to develop and commercialize DNA-based vaccine products for the treatment of chronic hepatitis B using Ichor’s TriGrid™ electroporation technology for administration. [Ichor Medical Systems, Inc.] Press Release

MEDI8897 Receives Fast Track Designation by the FDA for the Prevention of Respiratory Disease Caused by RSV in Infants
MedImmune announced that it has received fast track designation from the U.S. Food and Drug Administration (FDA) for the development of MEDI8897. This high-potency, extended half-life monoclonal antibody is being investigated for the prevention of lower respiratory tract illness caused by respiratory syncytial virus (RSV) in infants and young children. [MedImmune, LLC] Press Release

Gilead Submits New Drug Application to U.S. Food and Drug Administration for Fixed-Dose Combination of Emtricitabine/Tenofovir Alafenamide for HIV Treatment
Gilead Sciences, Inc. announced that it has submitted a New Drug Application to the U.S. Food and Drug Administration (FDA) for two doses of an investigational fixed-dose combination of emtricitabine and tenofovir alafenamide for the treatment of HIV-1 infection in adults and pediatric patients age 12 years and older, in combination with other HIV antiretroviral agents. [Gilead Sciences, Inc.] Press Release

Phase III Trial of the Merck and NewLink Genetics Investigational Ebola Vaccine Initiated in Sierra Leone
Merck and NewLink Genetics Corporation confirmed that the third, late-stage, clinical trial of their Ebola vaccine candidate rVSV-ZEBOV-GP has been initiated in Sierra Leone. [Merck & Co., Inc.] Press Release

Arrowhead Cleared to Proceed with Multiple Dose Phase IIb Study of ARC-520
Arrowhead Research Corporation announced that the United States Food and Drug Administration (FDA) informed the company that it can proceed with a multiple-dose Phase IIb clinical study of ARC-520, its clinical candidate for the treatment of chronic hepatitis B infection, under an investigational new drug application previously filed with the FDA. [Arrowhead Research Corporation] Press Release

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