Hybrids of the core protein of hepatitis B virus (HBcAg) have been designed which carry N-terminal insertions of B- and T-cell epitopes of HIV-1 an immunodominant B-epitope from gp41, a T-cell epitope from p34 pol, and a cluster of B- and T-cell epitopes from p17 gag. The hybrids have been synthesized using two expression systems-one based on the thermoinducible PR promoter of bacteriophage lambda and the other one based on phi 10 promoter of bacteriophage T7 with 3-5% and 7-14% yields, respectively. The hybrids have dual HBV and HIV-1 immunospecificity and are assembled into particles similar to those formed by the protein carrier HBcAg. Sandwich ELISA and immune electron microscopy revealed that HIV-1 epitopes are exposed on the surface of the particles.
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EBioMedicine
January 2025
Imperial College London, Department of Infectious Disease, UK. Electronic address:
Background: We report findings from an experimental medicine study of rationally designed prefusion stabilised native-like HIV envelope glycoprotein (Env) immunogens, representative of global circulating strains, delivered by sequential intramuscular injection.
Methods: Healthy adult volunteers were enrolled into one of five groups (A to E) each receiving a different schedule of one of two consensus Env immunogens (ConM SOSIP, ConS UFO, either unmodified or stabilised by chemical cross-linking, followed by a boost with two mosaic Env immunogens (Mos3.1 and Mos3.
AIDS Res Hum Retroviruses
December 2024
Department of Immunobiology, College of Medicine, University of Arizona, Tucson, Arizona, USA.
Despite advancements in antiretroviral therapy (ART) that reduces the viral load to undetectable levels and improve CD4 T cell counts, viral eradication has not been achieved due to HIV-1 persistence in resting CD4 T-cells. We, therefore, characterized the gene, which is essential for HIV-1 replication and pathogenesis, from 20 virologically controlled aging individuals with HIV (HIV) on long-term ART and improved CD4 T-cell counts, with a particular focus on older individuals. Peripheral blood mononuclear cell genomic DNA from HIV were used to amplify gene by polymerase chain reaction followed by nucleotide sequencing and analysis.
View Article and Find Full Text PDFVaccine
December 2024
Mucosal Immunoogy Laboratory, Biomedicine Research Unit, Faculty of Higher Studies Iztacala, National Autonomous University of Mexico. Avenida de los Barrios 1, Los Reyes Iztacala, Tlalnepantla, Estado de México 54090, Mexico. Electronic address:
The development of a protective HIV vaccine remains a challenge given the high antigenic diversity and mutational rate of the virus, which leads to viral escape and establishment of reservoirs in the host. Modern antigen design can guide immune responses towards conserved sites, consensus sequences or normally subdominant epitopes, thus enabling the development of broadly neutralizing antibodies and polyfunctional lymphocyte responses. Conventional epitope vaccines can often be impaired by low immunogenicity, a limitation that may be overcome by using a carrier system.
View Article and Find Full Text PDFMol Biol (Mosk)
December 2024
Gamaleya Federal Research Center of Epidemiology and Microbiology, Moscow, 123098 Russia.
Previously obtained highly immunogenic Env-VLPs ensure overcoming the natural resistance of HIV-1 surface proteins associated with their low level of incorporation and inaccessibility of conserved epitopes to induce neutralizing antibodies. We also adopted this technology to modify Env trimers of the ZM53(T/F) strain to produce Env-VLPs by recombinant vaccinia viruses (rVVs). For VLP production, rVVs expressing Env, Gag-Pol (HIV-1/SIV), and the cowpox virus hr gene, which overcomes the restriction of vaccinia virus replication in CHO cells, were used.
View Article and Find Full Text PDFFront Immunol
December 2024
Department of Medicine Solna, Division of Infectious Diseases, Karolinska Institutet, Division of Infectious Diseases, Karolinska University Hospital, Center for Molecular Medicine, Stockholm, Sweden.
Introduction: Chronic immune activation is a hallmark of human immunodeficiency virus (HIV) infection that significantly impacts disease pathogenesis. However, in-depth studies characterizing the immunological landscape of the ectocervix during chronic HIV infection remain scarce despite the importance of this tissue site for HIV transmission.
Methods: Ectocervical tissue samples were obtained from antiretroviral-naïve HIV-seropositive and -seronegative Kenyan female sex workers.
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