Baculovirus Capsid Display Potentiates OVA Cytotoxic and Innate Immune Responses

Paula Molinari,María J Gravisaco,María I Crespo,Gabriel Morón,Oscar Taboga,Mauricio Martins Rodrigues

doi:10.1371/journal.pone.0024108

Abstract

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.

Highlights

The development of vaccines to prevent diseases for which no vaccine currently exists, such as AIDS or malaria, or to treat chronic infections or cancers, as well as the improvement of efficacy and safety of existing vaccines, remains a high priority
The baculovirus system has been previously shown to be capable of displaying a foreign protein on the virion surface [9,10,11,12,22], usually by using GP64, its major surface glycoprotein
BV can reach the cytoplasm of mammalian cells by a mechanism similar to the one used in insect cells [17,23,24,25], with this process starting with endocytosis, being followed by acidinduced fusion of the virus envelope to the endosome and by escape of the virus capsid to the cytosol

Summary

Introduction

The development of vaccines to prevent diseases for which no vaccine currently exists, such as AIDS or malaria, or to treat chronic infections or cancers, as well as the improvement of efficacy and safety of existing vaccines, remains a high priority. The development of such vaccines requires strategies capable of stimulating CD8 cytotoxic T lymphocytes (CTLs) and to deliver antigen to MHC class I molecules. As BV cannot replicate in vertebrate hosts [1,2], they are considered safe. Their low cytotoxicity, their inability to replicate in mammalian cells and the absence of pre-existing antibodies, make BV candidates for gene therapy, expression vaccines and vector display applications. To the best of our knowledge, there are to date no studies reporting that BV have developed strategies to escape from immune surveillance and could hamper immunogenicity, probably because mammals are not their natural hosts

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Conclusion