Abstract
Understanding CD8+ T cell responses generated by live virus vectors is critical for the rational design of next generation HIV CTL-based vaccines. We used recombinant influenza viruses expressing the HIV Env311-320 peptide in the neuraminidase stalk to study response magnitude, cytokine production and repertoire diversity for the elicited CD8+ DdEnv311 CTL set. The insertion of the CD8+ DdEnv311 epitope into the NA stalk resulted in a decrease in viral fitness that was reflected in lower lung viral titres. While not affecting the magnitude of endogenous primary influenza-specific responses, the introduction of the DdEnv311 CD8+ T cell epitope altered the hierarchy of responses following secondary challenge. The CD8+ KdNP147 response increased 9-fold in the spleen following secondary infection whereas the CD8+ DdEnv311 response increased 15-fold in the spleen. Moreover, this study is the first to describe narrowing of CD8+ TCR repertoire diversity in the context of an evolving secondary immune response against influenza A virus. Analysis of Vβ bias for CD8+ DdEnv311 T cell responses showed a narrowing of CD8+ Vβ8.1/8.2 DdEnv311 TCR repertoire diversity. This work further emphasizes the importance of understanding vaccine-induced CD8+ T cell responses. Crown
Original language | English |
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Pages (from-to) | 6755-6761 |
Number of pages | 7 |
Journal | Vaccine |
Volume | 27 |
Issue number | 48 |
DOIs | |
Publication status | Published - 12 Nov 2009 |
Externally published | Yes |
Keywords
- CD8+ T cells
- TCR diversity
- Vaccination