Promoter control over foreign antigen expression in a murine cytomegalovirus vaccine vector

P.T. Cunningham; M.L. Lloyd; N.L. Harvey; E. Williams; C.M. Hardy; A.J. Redwood; M.A. Lawson; G.R. Shellam

doi:10.1016/j.vaccine.2010.03.012

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Promoter control over foreign antigen expression in a murine cytomegalovirus vaccine vector

Journal article

Peer reviewed

Promoter control over foreign antigen expression in a murine cytomegalovirus vaccine vector

P.T. Cunningham, M.L. Lloyd, N.L. Harvey, E. Williams, C.M. Hardy, A.J. Redwood, M.A. Lawson and G.R. Shellam

Vaccine, Vol.29(1), pp.141-151

2010

DOI: https://doi.org/10.1016/j.vaccine.2010.03.012

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Abstract

Previous studies have reported on the development of a recombinant murine cytomegalovirus (rMCMV) containing the mouse zona pellucida 3 (mZP3) gene for use as a virally vectored immunocontraceptive (VVIC). This study aimed to alter promoter control over foreign antigen expression and cellular localisation of the antigen expressed in order to overcome virus attenuation previously encountered. Early studies reported on the mZP3 gene expressed by a strong constitutive human cytomegalovirus immediate-early 1 promoter (pHCMV IE1). This virus was able to induce >90% infertility in BALB/c mice despite being heavily attenuated in vivo. In this study the mZP3 was placed under the control of the MCMV early 1 (pMCMV E1) promoter and the inducible tetracycline promoter (Tet-On). In both instances the recombinant virus was able to induce infertility in directly infected mice. However, the viruses remained attenuated. This study demonstrated the capacity to manipulate the nature of the immune response by altering promoter control over foreign antigen expression and cellular localisation of the expressed antigen. We were able to demonstrate that by using the MCMV E1 promoter it was still possible to sterilize female BALB/c mice with an MCMV vector expressing mZP3. The use of the MCMV E1 promoter provides an added level of safety to any MCMV based VVIC approach as it only allows for transgene expression in MCMV permissive cells.

Details

Title: Promoter control over foreign antigen expression in a murine cytomegalovirus vaccine vector
Authors/Creators: P.T. Cunningham (Author/Creator) - The University of Western Australia
M.L. Lloyd (Author/Creator) - School of Pathology and Laboratory Medicine
N.L. Harvey (Author/Creator) - The University of Western Australia
E. Williams (Author/Creator) - The University of Western Australia
C.M. Hardy (Author/Creator) - Commonwealth Scientific and Industrial Research Organisation
A.J. Redwood (Author/Creator) - School of Pathology and Laboratory Medicine
M.A. Lawson (Author/Creator) - Animal Care Services
G.R. Shellam (Author/Creator) - School of Pathology and Laboratory Medicine
Publication Details: Vaccine, Vol.29(1), pp.141-151
Publisher: Elsevier BV
Identifiers: 991005543366907891
Copyright: © 2010 Elsevier Ltd
Murdoch Affiliation: Murdoch University
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.161 Virology - Identification & Sequencing; 1.161.711 Cytomegalovirus Infections
Web Of Science research areas: Immunology; Medicine, Research & Experimental
ESI research areas: Immunology