Multiple tandem copies of conserved gp41 epitopes incorporated in gag virus-like particles elicit systemic and mucosal antibodies in an optimized heterologous vector delivery regimen.
Summary of "Multiple tandem copies of conserved gp41 epitopes incorporated in gag virus-like particles elicit systemic and mucosal antibodies in an optimized heterologous vector delivery regimen."
Induction of neutralizing antibodies to prevent HIV infection, especially at the mucosa, is a critical goal of future vaccines. In this study, we have designed chimeric HIV-gag virus-like particles (VLPs) that contain multiple copies of the two highly conserved gp41 membrane-proximal external region (MPER) epitopes, ELDKWA and NWFDIT, with the objective of generating high titers of MPER-specific antibodies. We have shown that the implementation of optimized vector design, delivery regimens and appropriate delivery methods is critical to significantly increase epitope-specific antibody titers. One goal of the methods that were tested and employed was to generate high levels of mucosal MPER-specific antibodies, as mucosal immune induction could play a key role in preventing HIV infection. We also tested a design strategy that incorporated multiple repeats of the MPER epitopes within gag, which significantly increased specific antibody titers, systemically and mucosally. This alternative design strategy and the implementation of optimized heterologous immunization regimens can serve to 'immuno-focus' and significantly increase epitope-specific titers.
Affiliation
Michael G. DeGroote Institute for Infectious Disease Research, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
Journal Details
This article was published in the following journal.
Name: Vaccine
ISSN: 1873-2518
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20723627
- DOI: http://dx.doi.org/10.1016/j.vaccine.2010.08.009
Medical and Biotech [MESH] Definitions
Tandem Repeat Sequences
Copies of DNA sequences which lie adjacent to each other in the same orientation (direct tandem repeats) or in the opposite direction to each other (INVERTED TANDEM REPEATS).
Hiv Envelope Protein Gp41
Transmembrane envelope protein of the HUMAN IMMUNODEFICIENCY VIRUS which is encoded by the HIV env gene. It has a molecular weight of 41,000 and is glycosylated. The N-terminal part of gp41 is thought to be involved in CELL FUSION with the CD4 ANTIGENS of T4 LYMPHOCYTES, leading to syncytial formation. Gp41 is one of the most common HIV antigens detected by IMMUNOBLOTTING.
Repetitive Sequences, Nucleic Acid
Sequences of DNA or RNA that occur in multiple copies. There are several types: INTERSPERSED REPETITIVE SEQUENCES are copies of transposable elements (DNA TRANSPOSABLE ELEMENTS or RETROELEMENTS) dispersed throughout the genome. TERMINAL REPEAT SEQUENCES flank both ends of another sequence, for example, the long terminal repeats (LTRs) on RETROVIRUSES. Variations may be direct repeats, those occurring in the same direction, or inverted repeats, those opposite to each other in direction. TANDEM REPEAT SEQUENCES are copies which lie adjacent to each other, direct or inverted (INVERTED REPEAT SEQUENCES).
Ubiquitin C
A single protein comprised of tandem repeats of the UBIQUITIN 78-amino acid sequence. It is a product of the polyubiquitin gene which contains multiple copies of the ubiquitin coding sequence. Proteolytic processing of ubiquitin C results in the formation of individual ubiquitin molecules. This protein is distinct from POLYUBIQUITIN, which is a protein formed through isopeptide linkage of multiple ubiquitin species.
Vaccines, Virus-like Particle
Vaccines using supra-molecular structures composed of multiple copies of recombinantly expressed viral structural proteins. They are often antigentically indistinguishable from the virus from which they were derived.
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