Modulation of cellular and humoral immune responses to a multiepitopic HIV-1 DNA vaccine by interleukin-18 DNA immunization/viral protein boost.

Abstract:

:In this study, the impact of Th1-inducing cytokine gene co-delivery and antigen boosting on humoral and cellular responses induced by multiepitopic DNA immunization in mice have been investigated. Intramuscular injection of mixed DNA constructs encoding for HIV-1 Gag, Tat and Nef proteins, co-administered with the DNA encoding for interleukin-18 (IL-18) have been used. The effect of boosting with the recombinant proteins was also evaluated on the outcome of the responses in DNA-primed mice. It was demonstrated that at least two DNA immunizations were necessary to generate virus specific Th-1 responses detected by the presence of cytotoxic T lymphocyte (CTL) and by the secretion of IL-2 and IFN-gamma, but not IL-4 and IL-10, in antigen-stimulated splenocyte cultures. Interestingly, co-delivery of Th-1-inducing IL-18 gene was able to shorten by 2 weeks, the CTL induction time, and to increase the antigen-induced secretion of IL-2 and IFN-gamma. Furthermore, IL-18 co-delivery enhanced antigen-specific lymphoproliferative responses, and this was most evident in mice that were primed and boosted with plasmid DNA. However, the induction of detectable antibodies in mice required two DNA vaccinations and a protein boost. In contrast to the effects on cell-mediated immunity, co-administration of IL-18-plasmid resulted in decreased antibody titers against viral proteins.

journal_name

Vaccine

journal_title

Vaccine

authors

Billaut-Mulot O,Idziorek T,Loyens M,Capron A,Bahr GM

doi

10.1016/s0264-410x(01)00004-4

subject

Has Abstract

pub_date

2001-04-06 00:00:00

pages

2803-11

issue

20-22

eissn

0264-410X

issn

1873-2518

pii

S0264410X01000044

journal_volume

19

pub_type

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