A live guinea pig cytomegalovirus vaccine deleted of three putative immune evasion genes is highly attenuated but remains immunogenic in a vaccine/challenge model of congenital cytomegalovirus infection

Megan M. Crumpler; K. Yeon Choi; Michael A. McVoy; Mark R. Schleiss

doi:10.1016/j.vaccine.2009.04.036

A live guinea pig cytomegalovirus vaccine deleted of three putative immune evasion genes is highly attenuated but remains immunogenic in a vaccine/challenge model of congenital cytomegalovirus infection

Megan M. Crumpler, K. Yeon Choi, Michael A. McVoy, Mark R. Schleiss

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

Abstract

Live attenuated vaccines for prevention of congenital cytomegalovirus infections encode numerous immune evasion genes. Their removal could potentially improve vaccine safety and efficacy. To test this hypothesis, three genes encoding MHC class I homologs (presumed NK evasins) were deleted from the guinea pig cytomegalovirus genome and the resulting virus, 3DX, was evaluated as a live attenuated vaccine in the guinea pig congenital infection model. 3DX was attenuated in vivo but not in vitro. Vaccination with 3DX produced elevated cytokine levels and higher antibody titers than wild type (WT) virus while avidity and neutralizing titers were similar. Protection, assessed by maternal viral loads and pup mortality following pathogenic viral challenge during pregnancy, was comparable between 3DX and WT and significant compared to naïve animals. These results suggest that the safety and perhaps efficacy of live attenuated human cytomegalovirus vaccines could be enhanced by deletion of viral immunomodulatory genes.

Original language	English (US)
Pages (from-to)	4209-4218
Number of pages	10
Journal	Vaccine
Volume	27
Issue number	31
DOIs	https://doi.org/10.1016/j.vaccine.2009.04.036
State	Published - Jun 24 2009

Bibliographical note

Funding Information:
The authors are grateful to Dong Yu for providing plasmid pYD-Tn1721, to Søren Warming for providing SW102 E. coli cells, and to Jodi Anderson and Michael Leviton for their technical assistance. We also thank Julie McVoy for providing the Excel program used for curve fitting and IC 50 determinations. This work was supported by grants R01HD044864 and R01HD038416 from the National Institutes of Health.

Keywords

Animal models
Congenital cytomegalovirus infection
Cytomegalovirus vaccines
Guinea pig cytomegalovirus
MHC class I homolog
Viral immune evasion

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Publisher link

10.1016/j.vaccine.2009.04.036

Find It

Find It at U of M Libraries

Cite this

A live guinea pig cytomegalovirus vaccine deleted of three putative immune evasion genes is highly attenuated but remains immunogenic in a vaccine/challenge model of congenital cytomegalovirus infection. / Crumpler, Megan M.; Choi, K. Yeon; McVoy, Michael A. et al.
In: Vaccine, Vol. 27, No. 31, 24.06.2009, p. 4209-4218.

Research output: Contribution to journal › Article › peer-review

@article{b7a8e955046b469fa766fb185453f798,

title = "A live guinea pig cytomegalovirus vaccine deleted of three putative immune evasion genes is highly attenuated but remains immunogenic in a vaccine/challenge model of congenital cytomegalovirus infection",

abstract = "Live attenuated vaccines for prevention of congenital cytomegalovirus infections encode numerous immune evasion genes. Their removal could potentially improve vaccine safety and efficacy. To test this hypothesis, three genes encoding MHC class I homologs (presumed NK evasins) were deleted from the guinea pig cytomegalovirus genome and the resulting virus, 3DX, was evaluated as a live attenuated vaccine in the guinea pig congenital infection model. 3DX was attenuated in vivo but not in vitro. Vaccination with 3DX produced elevated cytokine levels and higher antibody titers than wild type (WT) virus while avidity and neutralizing titers were similar. Protection, assessed by maternal viral loads and pup mortality following pathogenic viral challenge during pregnancy, was comparable between 3DX and WT and significant compared to na{\"i}ve animals. These results suggest that the safety and perhaps efficacy of live attenuated human cytomegalovirus vaccines could be enhanced by deletion of viral immunomodulatory genes.",

keywords = "Animal models, Congenital cytomegalovirus infection, Cytomegalovirus vaccines, Guinea pig cytomegalovirus, MHC class I homolog, Viral immune evasion",

author = "Crumpler, {Megan M.} and Choi, {K. Yeon} and McVoy, {Michael A.} and Schleiss, {Mark R.}",

note = "Funding Information: The authors are grateful to Dong Yu for providing plasmid pYD-Tn1721, to S{\o}ren Warming for providing SW102 E. coli cells, and to Jodi Anderson and Michael Leviton for their technical assistance. We also thank Julie McVoy for providing the Excel program used for curve fitting and IC 50 determinations. This work was supported by grants R01HD044864 and R01HD038416 from the National Institutes of Health.",

year = "2009",

month = jun,

day = "24",

doi = "10.1016/j.vaccine.2009.04.036",

language = "English (US)",

volume = "27",

pages = "4209--4218",

journal = "Vaccine",

issn = "0264-410X",

publisher = "Elsevier BV",

number = "31",

}

TY - JOUR

T1 - A live guinea pig cytomegalovirus vaccine deleted of three putative immune evasion genes is highly attenuated but remains immunogenic in a vaccine/challenge model of congenital cytomegalovirus infection

AU - Crumpler, Megan M.

AU - Choi, K. Yeon

AU - McVoy, Michael A.

AU - Schleiss, Mark R.

N1 - Funding Information: The authors are grateful to Dong Yu for providing plasmid pYD-Tn1721, to Søren Warming for providing SW102 E. coli cells, and to Jodi Anderson and Michael Leviton for their technical assistance. We also thank Julie McVoy for providing the Excel program used for curve fitting and IC 50 determinations. This work was supported by grants R01HD044864 and R01HD038416 from the National Institutes of Health.

PY - 2009/6/24

Y1 - 2009/6/24

N2 - Live attenuated vaccines for prevention of congenital cytomegalovirus infections encode numerous immune evasion genes. Their removal could potentially improve vaccine safety and efficacy. To test this hypothesis, three genes encoding MHC class I homologs (presumed NK evasins) were deleted from the guinea pig cytomegalovirus genome and the resulting virus, 3DX, was evaluated as a live attenuated vaccine in the guinea pig congenital infection model. 3DX was attenuated in vivo but not in vitro. Vaccination with 3DX produced elevated cytokine levels and higher antibody titers than wild type (WT) virus while avidity and neutralizing titers were similar. Protection, assessed by maternal viral loads and pup mortality following pathogenic viral challenge during pregnancy, was comparable between 3DX and WT and significant compared to naïve animals. These results suggest that the safety and perhaps efficacy of live attenuated human cytomegalovirus vaccines could be enhanced by deletion of viral immunomodulatory genes.

AB - Live attenuated vaccines for prevention of congenital cytomegalovirus infections encode numerous immune evasion genes. Their removal could potentially improve vaccine safety and efficacy. To test this hypothesis, three genes encoding MHC class I homologs (presumed NK evasins) were deleted from the guinea pig cytomegalovirus genome and the resulting virus, 3DX, was evaluated as a live attenuated vaccine in the guinea pig congenital infection model. 3DX was attenuated in vivo but not in vitro. Vaccination with 3DX produced elevated cytokine levels and higher antibody titers than wild type (WT) virus while avidity and neutralizing titers were similar. Protection, assessed by maternal viral loads and pup mortality following pathogenic viral challenge during pregnancy, was comparable between 3DX and WT and significant compared to naïve animals. These results suggest that the safety and perhaps efficacy of live attenuated human cytomegalovirus vaccines could be enhanced by deletion of viral immunomodulatory genes.

KW - Animal models

KW - Congenital cytomegalovirus infection

KW - Cytomegalovirus vaccines

KW - Guinea pig cytomegalovirus

KW - MHC class I homolog

KW - Viral immune evasion

UR - http://www.scopus.com/inward/record.url?scp=67349171033&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67349171033&partnerID=8YFLogxK

U2 - 10.1016/j.vaccine.2009.04.036

DO - 10.1016/j.vaccine.2009.04.036

M3 - Article

C2 - 19389443

AN - SCOPUS:67349171033

SN - 0264-410X

VL - 27

SP - 4209

EP - 4218

JO - Vaccine

JF - Vaccine

IS - 31

ER -

A live guinea pig cytomegalovirus vaccine deleted of three putative immune evasion genes is highly attenuated but remains immunogenic in a vaccine/challenge model of congenital cytomegalovirus infection

Abstract

Bibliographical note

Keywords

UN SDGs

Publisher link

Find It

Other files and links

Fingerprint

Cite this