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Modified Vaccinia Virus Ankara Can Induce Optimal CD8 + T Cell Responses to Directly Primed Antigens Depending on Vaccine Design.
- Source :
-
Journal of virology [J Virol] 2019 Oct 15; Vol. 93 (21). Date of Electronic Publication: 2019 Oct 15 (Print Publication: 2019). - Publication Year :
- 2019
-
Abstract
- A variety of strains of vaccinia virus (VACV) have been used as recombinant vaccine vectors with the aim of inducing robust CD8 <superscript>+</superscript> T cell immunity. While much of the pioneering work was done with virulent strains, such as Western Reserve (WR), attenuated strains such as modified vaccinia virus Ankara (MVA) are more realistic vectors for clinical use. To unify this literature, side-by-side comparisons of virus strains are required. Here, we compare the form of antigen that supports optimal CD8 <superscript>+</superscript> T cell responses for VACV strains WR and MVA using equivalent constructs. We found that for multiple antigens, minimal antigenic constructs (epitope minigenes) that prime CD8 <superscript>+</superscript> T cells via the direct presentation pathway elicited optimal responses from both vectors, which was surprising because this finding contradicts the prevailing view in the literature for MVA. We then went on to explore the discrepancy between current and published data for MVA, finding evidence that the expression locus and in some cases the presence of the viral thymidine kinase may influence the ability of this strain to prime optimal responses from antigens that require direct presentation. This extends our knowledge of the design parameters for VACV vectored vaccines, especially those based on MVA. IMPORTANCE Recombinant vaccines based on vaccinia virus and particularly attenuated strains such as MVA are in human clinical trials, but due to the complexity of these large vectors much remains to be understood about the design parameters that alter their immunogenicity. Previous work had found that MVA vectors should be designed to express stable protein in order to induce robust immunity by CD8 <superscript>+</superscript> (cytotoxic) T cells. Here, we found that the primacy of stable antigen is not generalizable to all designs of MVA and may depend where a foreign antigen is inserted into the MVA genome. This unexpected finding suggests that there is an interaction between genome location and the best form of antigen for optimal T cell priming in MVA and thus possibly other vaccine vectors. It also highlights that our understanding of antigen presentation by even the best studied of vaccine vectors remains incomplete.<br /> (Copyright © 2019 Wong et al.)
- Subjects :
- Animals
Antigens, Viral genetics
CD8-Positive T-Lymphocytes metabolism
Female
Genome, Viral
Immunization
Mice
Mice, Inbred C57BL
Ovalbumin genetics
Ovalbumin immunology
Thymidine Kinase genetics
Vaccinia metabolism
Vaccinia virology
Vaccinia virus classification
Viral Envelope Proteins genetics
Viral Envelope Proteins immunology
Viral Proteins genetics
Viral Proteins immunology
Antigens, Viral immunology
CD8-Positive T-Lymphocytes immunology
Peptide Fragments immunology
Thymidine Kinase metabolism
Vaccinia immunology
Vaccinia virus immunology
Viral Vaccines immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5514
- Volume :
- 93
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 31375596
- Full Text :
- https://doi.org/10.1128/JVI.01154-19