Mucosal HIV-1 pox virus prime-boost immunization induces high-avidity CD8 + T cells with regime-dependent cytokine/granzyme B profiles

Charani Ranasinghe, Stephen J. Turner, Craig McArthur, Duncan B. Sutherland, Jee Hye Kim, Peter C. Doherty, Ian A. Ramshaw

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Abstract

The quality of virus-specific CD8 + CTL immune responses generated by mucosal and systemic poxvinis prime-boost vaccines were evaluated in terms of T cell avidity and single-cell analysis of effector gene expression. Intranasal (I.N.) immunization regimes generated higher avidity CTL responses specific for HIV K d Gag 197-205 (amino acid sequence AMQMLKETI; H-2K d binding) compared with i.m. immunization regime. Single-cell RT-PCR of K d Gag 197-205 -specific mucosal and systemic CTL revealed that the cytokine and granzyme B expression profiles were dependent on both the route and time after immunization. The I.N./i.m.-immunized group elicited elevated number of CTL-expressing granzyme B mRNA from the genitomucosal sites compared with the i.m./i.m. regime. Interestingly, CTL generated after both I.N. or i.m. immunization demonstrated expression of Th2 cytokine IL-4 mRNA that was constitutively expressed over time, although lower numbers were observed after I.N./I.N. immunization. Results suggest that after immunization, Ag-speciflc CTL expression of IL-4 may be an inherent property of the highly evolved poxvirus vectors. Current observations indicate that the quality of CTL immunity generated after immunization can be influenced by the inherent property of vaccine vectors and route of vaccine delivery. A greater understanding of these factors will be crucial for the development of effective vaccines in the future.

Original languageEnglish
Pages (from-to)2370-2379
Number of pages10
JournalJournal of Immunology
Volume178
Issue number4
DOIs
Publication statusPublished - 15 Feb 2007
Externally publishedYes

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