Increased level and longevity of protective immune responses induced by DNA vaccine expressing the HIV-1 Env glycoprotein when combined with IL-21 and IL-15 gene delivery

Elizabeth Bolesta, Aleksandra Kowalczyk, Andrzej Wierzbicki, Cheryl Eppolito, Yutaro Kaneko, Masafumi Takiguchi, Leonidas Stamatatos, Protul A. Shrikant, Danuta Kozbor

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

We investigated the ability of a plasmid-derived IL-21 delivered alone or in combination with the IL-15 gene to regulate immune responses to the HIV-1 envelope (Env) glycoprotein induced by DNA vaccination. Mice were injected with the gp140ΔCFIHXB2/89.6 vector expressing a modified Env glycoprotein with C-terminal mutations intended to mimic a fusion intermediate, in which the most divergent region encoding the variable V1, V2, and V3 domains of CXCR4-tropic HxB2 virus was replaced with the dual-tropic 89.6 viral strain. Using a recombinant vaccinia virus expressing 89.6 Env glycoprotein (vBD3) in a mouse challenge model, we observed that IL-21 plasmid produced Sustained resistance to viral transmission when injected 5 days after DNA vaccination. Moreover, IL-21 in a synergistic manner with IL-15 expression vector augmented the vaccine-induced recall responses to the vBD3 challenge compared with those elicited by immunization in the presence of either cytokine alone. The synergistic combination of IL-21 and IL-15 plasmids promoted expansion of CD8+CD127+ memory T cell pools specific for a subdominant HLA-A2-restricted Env121-129 epitope (KLTPLCVTL). Our results also show that coimmunization with IL-21 and IL-15 plasmid combination resulted in enhanced CD8+ T cell function that was partially independent of CD4+ T cell help in mediating protection against vBD3 challenge. Furthermore, the use of IL-21 and IL-15 genes was able to increase Ab-dependent cellular cytotoxicity and complement-dependent lysis of Env-expressing target cells through augmentation of Env-specific IgG Ab levels. These data indicate that the plasmid-delivered IL-21 and IL-15 can increase the magnitude of the response to DNA vaccines.

Original languageEnglish (US)
Pages (from-to)177-191
Number of pages15
JournalJournal of Immunology
Volume177
Issue number1
StatePublished - Jul 1 2006
Externally publishedYes

Fingerprint

Interleukin-15
DNA Vaccines
HIV-1
Glycoproteins
Plasmids
Genes
T-Lymphocytes
Vaccination
HLA-A2 Antigen
Vaccinia virus
DNA
interleukin-21
Epitopes
Immunization
Vaccines
Immunoglobulin G
Cytokines
Viruses
Mutation

ASJC Scopus subject areas

  • Immunology

Cite this

Bolesta, E., Kowalczyk, A., Wierzbicki, A., Eppolito, C., Kaneko, Y., Takiguchi, M., ... Kozbor, D. (2006). Increased level and longevity of protective immune responses induced by DNA vaccine expressing the HIV-1 Env glycoprotein when combined with IL-21 and IL-15 gene delivery. Journal of Immunology, 177(1), 177-191.

Increased level and longevity of protective immune responses induced by DNA vaccine expressing the HIV-1 Env glycoprotein when combined with IL-21 and IL-15 gene delivery. / Bolesta, Elizabeth; Kowalczyk, Aleksandra; Wierzbicki, Andrzej; Eppolito, Cheryl; Kaneko, Yutaro; Takiguchi, Masafumi; Stamatatos, Leonidas; Shrikant, Protul A.; Kozbor, Danuta.

In: Journal of Immunology, Vol. 177, No. 1, 01.07.2006, p. 177-191.

Research output: Contribution to journalArticle

Bolesta, E, Kowalczyk, A, Wierzbicki, A, Eppolito, C, Kaneko, Y, Takiguchi, M, Stamatatos, L, Shrikant, PA & Kozbor, D 2006, 'Increased level and longevity of protective immune responses induced by DNA vaccine expressing the HIV-1 Env glycoprotein when combined with IL-21 and IL-15 gene delivery', Journal of Immunology, vol. 177, no. 1, pp. 177-191.
Bolesta, Elizabeth ; Kowalczyk, Aleksandra ; Wierzbicki, Andrzej ; Eppolito, Cheryl ; Kaneko, Yutaro ; Takiguchi, Masafumi ; Stamatatos, Leonidas ; Shrikant, Protul A. ; Kozbor, Danuta. / Increased level and longevity of protective immune responses induced by DNA vaccine expressing the HIV-1 Env glycoprotein when combined with IL-21 and IL-15 gene delivery. In: Journal of Immunology. 2006 ; Vol. 177, No. 1. pp. 177-191.
@article{58dc9be6944e4feb8563a87b1f6e4074,
title = "Increased level and longevity of protective immune responses induced by DNA vaccine expressing the HIV-1 Env glycoprotein when combined with IL-21 and IL-15 gene delivery",
abstract = "We investigated the ability of a plasmid-derived IL-21 delivered alone or in combination with the IL-15 gene to regulate immune responses to the HIV-1 envelope (Env) glycoprotein induced by DNA vaccination. Mice were injected with the gp140ΔCFIHXB2/89.6 vector expressing a modified Env glycoprotein with C-terminal mutations intended to mimic a fusion intermediate, in which the most divergent region encoding the variable V1, V2, and V3 domains of CXCR4-tropic HxB2 virus was replaced with the dual-tropic 89.6 viral strain. Using a recombinant vaccinia virus expressing 89.6 Env glycoprotein (vBD3) in a mouse challenge model, we observed that IL-21 plasmid produced Sustained resistance to viral transmission when injected 5 days after DNA vaccination. Moreover, IL-21 in a synergistic manner with IL-15 expression vector augmented the vaccine-induced recall responses to the vBD3 challenge compared with those elicited by immunization in the presence of either cytokine alone. The synergistic combination of IL-21 and IL-15 plasmids promoted expansion of CD8+CD127+ memory T cell pools specific for a subdominant HLA-A2-restricted Env121-129 epitope (KLTPLCVTL). Our results also show that coimmunization with IL-21 and IL-15 plasmid combination resulted in enhanced CD8+ T cell function that was partially independent of CD4+ T cell help in mediating protection against vBD3 challenge. Furthermore, the use of IL-21 and IL-15 genes was able to increase Ab-dependent cellular cytotoxicity and complement-dependent lysis of Env-expressing target cells through augmentation of Env-specific IgG Ab levels. These data indicate that the plasmid-delivered IL-21 and IL-15 can increase the magnitude of the response to DNA vaccines.",
author = "Elizabeth Bolesta and Aleksandra Kowalczyk and Andrzej Wierzbicki and Cheryl Eppolito and Yutaro Kaneko and Masafumi Takiguchi and Leonidas Stamatatos and Shrikant, {Protul A.} and Danuta Kozbor",
year = "2006",
month = "7",
day = "1",
language = "English (US)",
volume = "177",
pages = "177--191",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "1",

}

TY - JOUR

T1 - Increased level and longevity of protective immune responses induced by DNA vaccine expressing the HIV-1 Env glycoprotein when combined with IL-21 and IL-15 gene delivery

AU - Bolesta, Elizabeth

AU - Kowalczyk, Aleksandra

AU - Wierzbicki, Andrzej

AU - Eppolito, Cheryl

AU - Kaneko, Yutaro

AU - Takiguchi, Masafumi

AU - Stamatatos, Leonidas

AU - Shrikant, Protul A.

AU - Kozbor, Danuta

PY - 2006/7/1

Y1 - 2006/7/1

N2 - We investigated the ability of a plasmid-derived IL-21 delivered alone or in combination with the IL-15 gene to regulate immune responses to the HIV-1 envelope (Env) glycoprotein induced by DNA vaccination. Mice were injected with the gp140ΔCFIHXB2/89.6 vector expressing a modified Env glycoprotein with C-terminal mutations intended to mimic a fusion intermediate, in which the most divergent region encoding the variable V1, V2, and V3 domains of CXCR4-tropic HxB2 virus was replaced with the dual-tropic 89.6 viral strain. Using a recombinant vaccinia virus expressing 89.6 Env glycoprotein (vBD3) in a mouse challenge model, we observed that IL-21 plasmid produced Sustained resistance to viral transmission when injected 5 days after DNA vaccination. Moreover, IL-21 in a synergistic manner with IL-15 expression vector augmented the vaccine-induced recall responses to the vBD3 challenge compared with those elicited by immunization in the presence of either cytokine alone. The synergistic combination of IL-21 and IL-15 plasmids promoted expansion of CD8+CD127+ memory T cell pools specific for a subdominant HLA-A2-restricted Env121-129 epitope (KLTPLCVTL). Our results also show that coimmunization with IL-21 and IL-15 plasmid combination resulted in enhanced CD8+ T cell function that was partially independent of CD4+ T cell help in mediating protection against vBD3 challenge. Furthermore, the use of IL-21 and IL-15 genes was able to increase Ab-dependent cellular cytotoxicity and complement-dependent lysis of Env-expressing target cells through augmentation of Env-specific IgG Ab levels. These data indicate that the plasmid-delivered IL-21 and IL-15 can increase the magnitude of the response to DNA vaccines.

AB - We investigated the ability of a plasmid-derived IL-21 delivered alone or in combination with the IL-15 gene to regulate immune responses to the HIV-1 envelope (Env) glycoprotein induced by DNA vaccination. Mice were injected with the gp140ΔCFIHXB2/89.6 vector expressing a modified Env glycoprotein with C-terminal mutations intended to mimic a fusion intermediate, in which the most divergent region encoding the variable V1, V2, and V3 domains of CXCR4-tropic HxB2 virus was replaced with the dual-tropic 89.6 viral strain. Using a recombinant vaccinia virus expressing 89.6 Env glycoprotein (vBD3) in a mouse challenge model, we observed that IL-21 plasmid produced Sustained resistance to viral transmission when injected 5 days after DNA vaccination. Moreover, IL-21 in a synergistic manner with IL-15 expression vector augmented the vaccine-induced recall responses to the vBD3 challenge compared with those elicited by immunization in the presence of either cytokine alone. The synergistic combination of IL-21 and IL-15 plasmids promoted expansion of CD8+CD127+ memory T cell pools specific for a subdominant HLA-A2-restricted Env121-129 epitope (KLTPLCVTL). Our results also show that coimmunization with IL-21 and IL-15 plasmid combination resulted in enhanced CD8+ T cell function that was partially independent of CD4+ T cell help in mediating protection against vBD3 challenge. Furthermore, the use of IL-21 and IL-15 genes was able to increase Ab-dependent cellular cytotoxicity and complement-dependent lysis of Env-expressing target cells through augmentation of Env-specific IgG Ab levels. These data indicate that the plasmid-delivered IL-21 and IL-15 can increase the magnitude of the response to DNA vaccines.

UR - http://www.scopus.com/inward/record.url?scp=33745411739&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745411739&partnerID=8YFLogxK

M3 - Article

C2 - 16785513

AN - SCOPUS:33745411739

VL - 177

SP - 177

EP - 191

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 1

ER -