Insect Baculoviruses Strongly Potentiate Adaptive Immune Responses by Inducing Type I IFN

Hervás-Stubbs, Sandra; Rueda, Paloma; López, Lissette; Leclerc, Claude

doi:10.4049/jimmunol.178.4.2361

Cited by 155 publications

(56 citation statements)

References 43 publications

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“…Although it has been shown that BV have adjuvant properties when they are co-administered with particulate structures such as latex beads or virus-like particles (VLPs) [5] or tumor cells [7], in the present study we have observed that the delivery of antigen and adjuvant in the same BV particle rendered a stronger CTL response. Indeed, when soluble OVA was coadministered with BV-WT, it was necessary to immunize with 30 times more OVA than the quantity of OVA displayed by BV-OVA to attain the cytotoxic response achieved by BV-OVA.…”

Section: Discussioncontrasting

confidence: 63%

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Baculovirus Capsid Display Potentiates OVA Cytotoxic and Innate Immune Responses

et al. 2011

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Baculoviruses (BV) are DNA viruses that are pathogenic for insects. Although BV infect a range of mammalian cell types, they do not replicate in these cells. Indeed, the potential effects of these insect viruses on the immune responses of mammals are only just beginning to be studied. We show in this paper that a recombinant Autographa californica multiple nuclear polyhedrosis virus carrying a fragment of ovalbumin (OVA) on the VP39 capsid protein (BV-OVA) has the capacity to act as an adjuvant and vector of antigens in mice, thereby promoting specific CD4 and cytotoxic T cell responses against OVA. BV also induced in vivo maturation of dendritic cells and the production of inflammatory cytokines, thus promoting innate and adaptive immune responses. The OVA-specific response induced by BV-OVA was strong enough to reject a challenge with OVA-expressing melanoma cells (MO5 cells) and effectively prolonged survival of MO5 bearing mice. All these findings, together with the absence of pre-existing immunity to BV in humans and the lack of viral gene expression in mammalian cells, make BV a candidate for vaccination.

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Section: Discussioncontrasting

confidence: 63%

“…Hervas-Stubbs et al and others have demonstrated that BV have strong adjuvant properties, thereby promoting humoral and CTL responses against co-administered antigens, dendritic cell (DC) maturation and production of inflammatory mediators through mechanisms primarily mediated by IFN-α and β [5].…”

Section: Introductionmentioning

confidence: 99%

Baculovirus Capsid Display Potentiates OVA Cytotoxic and Innate Immune Responses

et al. 2011

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“…The "adjuvant" effect of baculovirus should also be considered. Baculovirus has the ability to induce innate immune responses through the Toll-like receptor 9 dependent signaling pathway, resulting in the production of various cytokines, including tumor necrosis factor-α, IL-6, and interferon [12,23,41,42]. In this study, a higher background of non-specific IFN-γ production was detected from mice injected with Bac-GED recombinant baculovirus, which further suggested the presence of the "adjuvant" effect of baculovirus.…”

Section: Discussionmentioning

confidence: 99%

A pseudotype baculovirus expressing the capsid protein of foot-and-mouth disease virus and a T-Cell immunogen shows enhanced immunogenicity in mice

Cao

Sun

et al. 2011

Virol J

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BackgroundFoot-and-mouth disease (FMD) is a highly contagious disease of livestock which causes severe economic loss in cloven-hoofed animals. Vaccination is still a major strategy in developing countries to control FMD. Currently, inactivated vaccine of FMDV has been used in many countries with limited success and safety concerns. Development of a novel effective vaccine is must.MethodsIn the present study, two recombinant pseudotype baculoviruses, one expressing the capsid of foot-and-mouth disease virus (FMDV) under the control of a cytomegalovirus immediate early enhancer/promoter (CMV-IE), and the other the caspid plus a T-cell immunogen coding region under a CAG promoter were constructed, and their expression was characterized in mammalian cells. In addition, their immunogenicity in a mouse model was investigated. The humoral and cell-mediated immune responses induced by pseudotype baculovirus were compared with those of inactivated vaccine.ResultsIndirect immunofluorescence assay (IFA) and indirect sandwich-ELISA (IS-ELISA) showed both recombinant baculoviruses (with or without T-cell epitopes) were transduced efficiently and expressed target proteins in BHK-21 cells. In mice, intramuscular inoculation of recombinants with 1 × 109 or 1 × 1010 PFU/mouse induced the production of FMDV-specific neutralizing antibodies and gamma interferon (IFN-γ). Furthermore, recombinant baculovirus with T-cell epitopes had better immunogenicity than the recombinant without T-cell epitopes as demonstrated by significantly enhanced IFN-γ production (P < 0.01) and higher neutralizing antibody titer (P < 0.05). Although the inactivated vaccine produced the highest titer of neutralizing antibodies, a lower IFN-γ expression was observed compared to the two recombinant pseudotype baculoviruses.ConclusionsThese results indicate that pseudotype baculovirus-mediated gene delivery could be a alternative strategy to develop a new generation of vaccines against FMDV infection.

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“…Cellular uptake of baculovirus and subsequent immune response enhancement may be due largely to the presence of the IFN-stimulatory baculovirus surface envelope glycoprotein gp64, which is responsible for host cell receptor binding and membrane fusion during viral entry by endocytosis [50]. In particular, gp64 protein is known to incorporate into the outer surface of baculovirus expressed Gag VLPs [3,26,47,51]. This has been additionally demonstrated in the current study, where both BV VLPs and PB VLPs are "coated" in host cell outer membrane, but gp64 would be available for incorporation only into the BV VLPs (Figure 4).…”

Section: Discussionmentioning

confidence: 99%

Use of the piggyBac transposon to create HIV-1 gag transgenic insect cell lines for continuous VLP production

et al. 2010

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BackgroundInsect baculovirus-produced Human immunodeficiency virus type 1 (HIV-1) Gag virus-like-particles (VLPs) stimulate good humoral and cell-mediated immune responses in animals and are thought to be suitable as a vaccine candidate. Drawbacks to this production system include contamination of VLP preparations with baculovirus and the necessity for routine maintenance of infectious baculovirus stock. We used piggyBac transposition as a novel method to create transgenic insect cell lines for continuous VLP production as an alternative to the baculovirus system.ResultsTransgenic cell lines maintained stable gag transgene integration and expression up to 100 cell passages, and although the level of VLPs produced was low compared to baculovirus-produced VLPs, they appeared similar in size and morphology to baculovirus-expressed VLPs. In a murine immunogenicity study, whereas baculovirus-produced VLPs elicited good CD4 immune responses in mice when used to boost a prime with a DNA vaccine, no boost response was elicited by transgenically produced VLPs.ConclusionTransgenic insect cells are stable and can produce HIV Pr55 Gag VLPs for over 100 passages: this novel result may simplify strategies aimed at making protein subunit vaccines for HIV. Immunogenicity of the Gag VLPs in mice was less than that of baculovirus-produced VLPs, which may be due to lack of baculovirus glycoprotein incorporation in the transgenic cell VLPs. Improved yield and immunogenicity of transgenic cell-produced VLPs may be achieved with the addition of further genetic elements into the piggyBac integron.

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Insect Baculoviruses Strongly Potentiate Adaptive Immune Responses by Inducing Type I IFN

Cited by 155 publications

References 43 publications

Baculovirus Capsid Display Potentiates OVA Cytotoxic and Innate Immune Responses

Baculovirus Capsid Display Potentiates OVA Cytotoxic and Innate Immune Responses

A pseudotype baculovirus expressing the capsid protein of foot-and-mouth disease virus and a T-Cell immunogen shows enhanced immunogenicity in mice

Use of the piggyBac transposon to create HIV-1 gag transgenic insect cell lines for continuous VLP production

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