Immunogenicities of intravenous and intramuscular administrations of modified vaccinia virus Ankara-based multi-CTL epitope vaccine for human immunodeficiency virus type 1 in mice.

Hanke, Tomáš; Blanchard, Tom; Schneider, Jörg; Ogg, Graham S.; Tan, Rusung; Becker, Marion; Gilbert, Sarah C.; Hill, Adrian V. S.; Smith, Geoffrey L.; McMichael, Andrew J.

doi:10.1099/0022-1317-79-1-83

Cited by 80 publications

(50 citation statements)

References 36 publications

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“…immunization using recombinant modified vaccinia virus Ankara expressing multiple CTL epitopes induced stronger CTL than did i.m. immunization (46). The direct infection of APCs and efficient presentation of Ag by direct priming could contribute to this phenomenon.…”

Section: Discussionmentioning

confidence: 99%

Direct Priming and Cross-Priming Contribute Differentially to the Induction of CD8+ CTL Following Exposure to Vaccinia Virus Via Different Routes

Shen¹,

Wong

Buck

et al. 2002

The Journal of Immunology

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To explore the relative importance of direct presentation vs cross-priming in the induction of CTL responses to viruses and viral vectors, we generated a recombinant vaccinia vector, vUS11, expressing the human CMV (HCMV) protein US11. US11 dislocates most allelic forms of human and murine MHC class I heavy chains from the lumen of the endoplasmic reticulum into the cytosol, where they are degraded by proteasomes. Expression of US11 dramatically decreased the presentation of viral Ag and CTL recognition of infected cells in vitro without significantly reducing total cell surface MHC class I levels. However, because US11 is an endoplasmic reticulum resident membrane protein, it cannot block presentation by non-infected cells that take up Ag through the cross-priming pathway. We show that the expression of US11 strongly inhibits the induction of primary CD8+ CTLs when the infection occurs via the i.p. or i.v. route, demonstrating that direct priming is critical for the induction of CTL responses to viral infections introduced via these routes. This effect is less dramatic following i.m. infection and is minimal after s.c. or intradermal infection. Thus, classic MHC class I Ag presentation and cross-priming contribute differentially to the induction of CD8+ CTLs following exposure to vaccinia virus via different routes.

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Section: Discussionmentioning

confidence: 99%

Direct Priming and Cross-Priming Contribute Differentially to the Induction of CD8+ CTL Following Exposure to Vaccinia Virus Via Different Routes

Shen¹,

Wong

Buck

et al. 2002

The Journal of Immunology

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“…This was similar to our previous experience with unstable recombinant proteins expressed from recombinant MVAs. 12,46 As CTL recognize peptide fragments derived from degraded HIV proteins, this is not a concern for the vaccine immunogenicity (see below).…”

Section: Expression In Human Cellsmentioning

confidence: 99%

Engineering RENTA, a DNA prime-MVA boost HIV vaccine tailored for Eastern and Central Africa

Nkolola

et al. 2004

Gene Ther

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For the development of human immunodeficiency virus type 1 (HIV-1) vaccines, traditional approaches inducing virus-neutralizing antibodies have so far failed. Thus the effort is now focused on elicitation of cellular immunity. We are currently testing in clinical trials in the United Kingdom and East Africa a T-cell vaccine consisting of HIV-1 clade A Gag-derived immunogen HIVA delivered in a prime-boost regimen by a DNA plasmid and modified vaccinia virus Ankara (MVA). Here, we describe engineering and preclinical development of a second immunogen RENTA, which will be used in combination with the present vaccine in a four-component DNA/HIVA-RENTA prime-MVA/HIVA-RENTA boost formulation. RENTA is a fusion protein derived from consensus HIV clade A sequences of Tat, reverse transcriptase, Nef and gp41. We inactivated the natural biological activities of the HIV components and confirmed immunogenicities of the pTHr.RENTA and MVA.RENTA vaccines in mice. Furthermore, we demonstrated in mice and rhesus monkeys broadening of HIVAelicited T-cell responses by a parallel induction of HIVA-and RENTA-specific responses recognizing multiple HIV epitopes.

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“…In contrast, the frequency of these peptide-specific, gamma interferon-producing cells was considerably less in splenocytes harvested from mice that had been immunized with the MVA.H vector, or with HSV:lacZ (as an irrelevant control). It should be noted that the MVA.H vector expresses the same immunodominant HIV-1 V3 loop peptide (RGPGRAFVTI) that is contained within the HSV:gp120 construct (14); it was therefore included in these initial experiments as a positive control.…”

Section: Vol 76 2002mentioning

confidence: 99%

Expression of Human Immunodeficiency Virus Type 1 gp120 from Herpes Simplex Virus Type 1-Derived Amplicons Results in Potent, Specific, and Durable Cellular and Humoral Immune Responses

Hocknell¹,

Wiley²,

Wang³

et al. 2002

J Virol

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Herpes simplex virus type 1 (HSV-1) infects a wide range of cells, including dendritic cells. Consequently, HSV-1 vectors may be capable of eliciting strong immune responses to vectored antigens. To test this hypothesis, an HSV-1 amplicon plasmid encoding human immunodeficiency virus type 1 gp120 was constructed, and murine immune responses to helper virus-free amplicon preparations derived from this construct were evaluated. Initial studies revealed that a single intramuscular (i.m.) injection of 10 6 infectious units (i.u.) of HSV:gp120 amplicon particles (HSV:gp120) elicited Env-specific cellular and humoral immune responses. A potent, CD8؉ -T-cell-mediated response to an H-2D d -restricted peptide from gp120 (RGPGRAFVTI) was measured by a gamma interferon ELISPOT and was confirmed by standard cytotoxic-T-lymphocyte assays. Immunoglobulin G enzyme-linked immunosorbent assay analysis showed the induction of a strong, Envspecific antibody response. An i.m. or an intradermal administration of HSV:gp120 at the tail base elicited a more potent cellular immune response than did an intraperitoneal (i.p.) inoculation, although an i.p. introduction generated a stronger humoral response. The immune response to HSV:gp120 was durable, with robust cellular and humoral responses persisting at 171 days after a single 10 6 -i.u. inoculation. The immune response to HSV:gp120 was also found to be dose dependent: as few as 10 4 i.u. elicited a strong T-cell response. Finally, HSV:gp120 elicited significant Env-specific cellular immune responses even in animals that had been previously infected with wild-type HSV-1. Taken together, these data strongly support the use of helper-free HSV-1 amplicon particles as vaccine delivery vectors.Genetically engineered herpesviruses have been successfully used for the development of vaccines against important animal diseases, including Aujesky's disease (pseudorabies virus), infectious bovine rhinotracheitis, and swine fever (hog cholera virus) (21,56,57). In addition, attenuated herpesviruses have been used for human vaccination (including the Towne strain of human cytomegalovirus and the Oka strain of varicellazoster virus) (5, 24, 38, 52). Both herpes simplex virus type 1 (HSV-1) and varicella-zoster virus have been used for the expression of foreign genes, since these viruses can accommodate large segments of exogenous DNA with little effect on virus replication (15, 43). Replication-competent and replication-defective gene replacement vectors based on both viruses are being explored as possible human immunodeficiency virus (HIV) vaccine delivery systems (32, 45). The appeal of this approach lies in part in the ability of herpesviruses to (i) elicit strong cytotoxic-T-lymphocyte (CTL) responses; (ii) infect mucosal surfaces; (iii) infect a broad range of cell types, including dendritic cells (1,23,30,40); and (iv) establish a state of persistence in the infected cell. The latter property may conceivably result in more durable immune responses to herpesvirus-based vaccines compared to man...

show abstract

Immunogenicities of intravenous and intramuscular administrations of modified vaccinia virus Ankara-based multi-CTL epitope vaccine for human immunodeficiency virus type 1 in mice.

Cited by 80 publications

References 36 publications

Direct Priming and Cross-Priming Contribute Differentially to the Induction of CD8+ CTL Following Exposure to Vaccinia Virus Via Different Routes

Direct Priming and Cross-Priming Contribute Differentially to the Induction of CD8+ CTL Following Exposure to Vaccinia Virus Via Different Routes

Engineering RENTA, a DNA prime-MVA boost HIV vaccine tailored for Eastern and Central Africa

Expression of Human Immunodeficiency Virus Type 1 gp120 from Herpes Simplex Virus Type 1-Derived Amplicons Results in Potent, Specific, and Durable Cellular and Humoral Immune Responses

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