An Attenuated Cytomegalovirus Vaccine with a Deletion of a Viral Chemokine Gene Is Protective against Congenital CMV Transmission in a Guinea Pig Model
Joint Authors
Choi, K. Yeon
Schleiss, Mark R.
Lacayo, Juan C.
Wey, Andrew
Leviton, Michael P.
Hernandez-Alvarado, Nelmary
Source
Clinical and Developmental Immunology
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-08-20
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
Development of a vaccine against congenital cytomegalovirus (CMV) infection is a public health priority, but CMVs encode immune evasion genes that complicate live virus vaccine design.
To resolve this problem, this study employed guanosyl phosphoribosyl transferase (gpt) mutagenesis to generate a recombinant guinea pig CMV (GPCMV) with a knockout of a viral chemokine gene, GPCMV MIP (gp1).
MIP deletion virus replicated with wild-type kinetics in cell culture but was attenuated in nonpregnant guinea pigs, demonstrating reduced viremia and reduced inflammation and histopathology (compared to a control virus with an intact GPCMV MIP gene) following footpad inoculation.
In spite of attenuation, the vaccine was immunogenic, eliciting antibody responses comparable to those observed in natural infection.
To assess its protective potential as a vaccine, either recombinant virus or placebo was used to immunize seronegative female guinea pigs.
Dams were challenged in the early 3rd trimester with salivary gland-adapted GPCMV.
Immunization protected against DNAemia (1/15 in vaccine group versus 12/13 in the control group, P<0.01).
Mean birth weights were significantly higher in pups born to vaccinated dams compared to controls (98.7 g versus 71.2 g, P<0.01).
Vaccination reduced pup mortality, from 35/50 (70%) in controls to 8/52 (15%) in the immunization group.
Congenital GPCMV infection was also reduced, from 35/50 (70%) in controls to 9/52 (17%) in the vaccine group (P<0.0001).
We conclude that deletion of an immune modulation gene can attenuate the pathogenicity of GPCMV while resulting in a viral vaccine that retains immunogenicity and demonstrates efficacy against congenital infection and disease.
American Psychological Association (APA)
Leviton, Michael P.& Lacayo, Juan C.& Choi, K. Yeon& Hernandez-Alvarado, Nelmary& Wey, Andrew& Schleiss, Mark R.. 2013. An Attenuated Cytomegalovirus Vaccine with a Deletion of a Viral Chemokine Gene Is Protective against Congenital CMV Transmission in a Guinea Pig Model. Clinical and Developmental Immunology،Vol. 2013, no. 2013, pp.1-12.
https://search.emarefa.net/detail/BIM-507070
Modern Language Association (MLA)
Leviton, Michael P.…[et al.]. An Attenuated Cytomegalovirus Vaccine with a Deletion of a Viral Chemokine Gene Is Protective against Congenital CMV Transmission in a Guinea Pig Model. Clinical and Developmental Immunology No. 2013 (2013), pp.1-12.
https://search.emarefa.net/detail/BIM-507070
American Medical Association (AMA)
Leviton, Michael P.& Lacayo, Juan C.& Choi, K. Yeon& Hernandez-Alvarado, Nelmary& Wey, Andrew& Schleiss, Mark R.. An Attenuated Cytomegalovirus Vaccine with a Deletion of a Viral Chemokine Gene Is Protective against Congenital CMV Transmission in a Guinea Pig Model. Clinical and Developmental Immunology. 2013. Vol. 2013, no. 2013, pp.1-12.
https://search.emarefa.net/detail/BIM-507070
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-507070