Although much effort has been expended on evaluating recombinant proteins and synthetic peptides as immunogens, they have generally proved incapable of inducing an efficient cytotoxic T-cell (CTL) response. Filamentous bacteriophage fd can display multiple copies of foreign peptides in the N-terminal region of its major coat protein pVIII, 2,700 copies of which make up the virus capsid. Here we show that fd virions displaying peptide RT2 (ILKEPVHGV), corresponding to residues 309-317 of the reverse transcriptase (RTase) of HIV-1, are able to prime a CTL response specific for this HIV-1 epitope in human cell lines. Successful priming also requires a T-helper epitope, pep23 (KDSWTVNDIQKLVGK), corresponding to residues 249-263 of HIV-1 RTase. Supplying this by displaying it on either the same or a separate bacteriophage virion led to activation of antigen-specific CD4+ T cells. Likewise, HLA-A2 transgenic mice immunized with bacteriophage virions displaying peptide RT2 were shown to mount an effective, specific anti-HIV-RT2 CTL response. This unexpected ability to elicit a designated cytolytic T-cell response, in addition to a B-cell response, has important implications for access to the class I major histocompatibility complex (MHC) loading compartment and the development of recombinant vaccines.
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http://dx.doi.org/10.1038/78490 | DOI Listing |
J Microbiol Biotechnol
November 2024
Fatemah AlMalki, Biology Department, College of Science and Humanities- Al Quwaiiyah, Shaqra University, Al Quwaiiyah 19257, Saudi Arabia.
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January 2025
Research Center for Molecular Biotechnology and Bioinformatics, Universitas Padjadjaran, Bandung 40133, Indonesia.
The emergence of new variants of SARS-CoV-2, including Alpha, Beta, Gamma, Delta, Omicron variants, and XBB sub-variants, contributes to the number of coronavirus cases worldwide. SARS-CoV-2 is a positive RNA virus with a genome of 29.9 kb that encodes four structural proteins: spike glycoprotein (S), envelope glycoprotein (E), membrane glycoprotein (M), and nucleocapsid glycoprotein (N).
View Article and Find Full Text PDFClin Exp Med
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Department of Hematology-Oncology, Imam Hossein Educational Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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View Article and Find Full Text PDFToxicon
January 2025
Universidade Estadual do Oeste do Paraná, Programa de Pós-Graduação em Biociências e Saúde (PPG-BCS), Cascavel, Brazil.
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View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Pharmacology & Toxicology, Cancer Center & Research Institute, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Oncolytic virotherapy has shown great promise in mediating targeted tumor destruction through tumor-selective replication and induction of anti-tumor immunity; however, obstacles remain for virus candidates to reach the clinic. These include avoiding neutralizing antibodies, preventing stimulation of the adaptive immune response during intravenous administration, and inducing sufficient apoptosis and immune activation so that the body's defense can work to eradicate systemic disease. We have developed a co-formulation of oncolytic viruses (OVs) with Imagent lipid-encapsulated, perfluorocarbon microbubbles (MBs) to protect the OVs from the innate and adaptive immune system.
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