MVA-vectored pentameric complex (PC) and gB vaccines improve pregnancy outcome after guinea pig CMV challenge, but only gB vaccine reduces vertical transmission

Heidi Contreras; Felix Wussow; Claudia Fernández-Alarcón; Craig Bierle; Jenny Nguyen; Don J. Diamond; Mark R. Schleiss

doi:10.3390/vaccines7040182

MVA-vectored pentameric complex (PC) and gB vaccines improve pregnancy outcome after guinea pig CMV challenge, but only gB vaccine reduces vertical transmission

Heidi Contreras, Felix Wussow, Claudia Fernández-Alarcón, Craig Bierle, Jenny Nguyen, Don J. Diamond, Mark R. Schleiss

Pediatrics - Infectious Disease

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

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Abstract

(1) Background: A congenital cytomegalovirus (cCMV) vaccine is a major research priority, but the essential glycoprotein target(s) remain unclear. We compared CMV gB (gpgB), gH/gL (gp75/gL), and pentameric complex (gpPC, composed of gH/gL/GP129/GP131/GP133) vaccines in a guinea pig CMV (GPCMV) congenital infection model. (2) Methods: Modified vaccinia virus Ankara (MVA) vaccines expressing GPCMV glycoproteins were used to immunize GPCMV-seronegative, female Hartley guinea pigs (three-dose series, 3 × 10⁷ pfu/dose). After pregnancy was established, the dams underwent an early third-trimester challenge with salivary gland (SG)-adapted GPCMV. (3) Results: All vaccines elicited GPCMV-specific binding and neutralizing antibodies. Preconception immunization resulted in 19.5-, 4.9-, and 698-fold reductions in maternal DNAemia in MVA-gp75/gL, MVA-gpPC and MVA-gpgB groups, respectively, at day 14, post-SG challenge. Vaccination improved pups’ birth weight and reduced mortality and congenital CMV transmission. In controls, cCMV infection was observed in 100% of pups (mean viral load in all visceral organs, 2.4 × 10⁴ genomes/mg), versus 50% in the gB group (visceral viral load, 9.4 × 10² genomes/mg; p < 0.05). No significant reductions in congenital transmission were noted in the MVA-gp75/gL and MVA-gpPC groups. (4) Conclusions: MVA-vectored gB, gH/gL, and PC vaccines were immunogenic, and protected against maternal DNAemia and pup mortality. These results support the inclusion of multiple glycoprotein complexes in a cCMV vaccine.

Original language	English (US)
Article number	182
Journal	Vaccines
Volume	7
Issue number	4
DOIs	https://doi.org/10.3390/vaccines7040182
State	Published - Dec 2019

Bibliographical note

Funding Information:
Funding: Research reported in this publication included work performed in the City of Hope Mass Spectrometry and Proteomics Core supported by the National Cancer Institute of the National Institutes of Health under award number P30CA033572. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Funding Information:
Research reported in this publication included work performed in the City of Hope Mass Spectrometry and Proteomics Core supported by the National Cancer Institute of the National Institutes of Health under award number P30CA033572. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Acknowledgments: We thank the Research Animal Resources (RAR) department at the University of Minnesota for excellent support in our guinea pig congenital infection studies. We also thank the City of Hope Mass Spectrometry and Proteomics Core for their assistance in this study.

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

Congenital cytomegalovirus infection
Cytomegalovirus glycoproteins
Cytomegalovirus vaccine
Guinea pig cytomegalovirus
Pentameric complex (PC)

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@article{3b4b24e29d7f4ccdbb4d1c6ad02b6452,

title = "MVA-vectored pentameric complex (PC) and gB vaccines improve pregnancy outcome after guinea pig CMV challenge, but only gB vaccine reduces vertical transmission",

abstract = "(1) Background: A congenital cytomegalovirus (cCMV) vaccine is a major research priority, but the essential glycoprotein target(s) remain unclear. We compared CMV gB (gpgB), gH/gL (gp75/gL), and pentameric complex (gpPC, composed of gH/gL/GP129/GP131/GP133) vaccines in a guinea pig CMV (GPCMV) congenital infection model. (2) Methods: Modified vaccinia virus Ankara (MVA) vaccines expressing GPCMV glycoproteins were used to immunize GPCMV-seronegative, female Hartley guinea pigs (three-dose series, 3 × 107 pfu/dose). After pregnancy was established, the dams underwent an early third-trimester challenge with salivary gland (SG)-adapted GPCMV. (3) Results: All vaccines elicited GPCMV-specific binding and neutralizing antibodies. Preconception immunization resulted in 19.5-, 4.9-, and 698-fold reductions in maternal DNAemia in MVA-gp75/gL, MVA-gpPC and MVA-gpgB groups, respectively, at day 14, post-SG challenge. Vaccination improved pups{\textquoteright} birth weight and reduced mortality and congenital CMV transmission. In controls, cCMV infection was observed in 100% of pups (mean viral load in all visceral organs, 2.4 × 104 genomes/mg), versus 50% in the gB group (visceral viral load, 9.4 × 102 genomes/mg; p < 0.05). No significant reductions in congenital transmission were noted in the MVA-gp75/gL and MVA-gpPC groups. (4) Conclusions: MVA-vectored gB, gH/gL, and PC vaccines were immunogenic, and protected against maternal DNAemia and pup mortality. These results support the inclusion of multiple glycoprotein complexes in a cCMV vaccine.",

keywords = "Congenital cytomegalovirus infection, Cytomegalovirus glycoproteins, Cytomegalovirus vaccine, Guinea pig cytomegalovirus, Pentameric complex (PC)",

author = "Heidi Contreras and Felix Wussow and Claudia Fern{\'a}ndez-Alarc{\'o}n and Craig Bierle and Jenny Nguyen and Diamond, {Don J.} and Schleiss, {Mark R.}",

note = "Funding Information: Funding: Research reported in this publication included work performed in the City of Hope Mass Spectrometry and Proteomics Core supported by the National Cancer Institute of the National Institutes of Health under award number P30CA033572. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: Research reported in this publication included work performed in the City of Hope Mass Spectrometry and Proteomics Core supported by the National Cancer Institute of the National Institutes of Health under award number P30CA033572. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Acknowledgments: We thank the Research Animal Resources (RAR) department at the University of Minnesota for excellent support in our guinea pig congenital infection studies. We also thank the City of Hope Mass Spectrometry and Proteomics Core for their assistance in this study. Publisher Copyright: {\textcopyright} 2019 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2019",

month = dec,

doi = "10.3390/vaccines7040182",

language = "English (US)",

volume = "7",

journal = "Vaccines",

issn = "2076-393X",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "4",

}

TY - JOUR

T1 - MVA-vectored pentameric complex (PC) and gB vaccines improve pregnancy outcome after guinea pig CMV challenge, but only gB vaccine reduces vertical transmission

AU - Contreras, Heidi

AU - Wussow, Felix

AU - Fernández-Alarcón, Claudia

AU - Bierle, Craig

AU - Nguyen, Jenny

AU - Diamond, Don J.

AU - Schleiss, Mark R.

N1 - Funding Information: Funding: Research reported in this publication included work performed in the City of Hope Mass Spectrometry and Proteomics Core supported by the National Cancer Institute of the National Institutes of Health under award number P30CA033572. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: Research reported in this publication included work performed in the City of Hope Mass Spectrometry and Proteomics Core supported by the National Cancer Institute of the National Institutes of Health under award number P30CA033572. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Acknowledgments: We thank the Research Animal Resources (RAR) department at the University of Minnesota for excellent support in our guinea pig congenital infection studies. We also thank the City of Hope Mass Spectrometry and Proteomics Core for their assistance in this study. Publisher Copyright: © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2019/12

Y1 - 2019/12

N2 - (1) Background: A congenital cytomegalovirus (cCMV) vaccine is a major research priority, but the essential glycoprotein target(s) remain unclear. We compared CMV gB (gpgB), gH/gL (gp75/gL), and pentameric complex (gpPC, composed of gH/gL/GP129/GP131/GP133) vaccines in a guinea pig CMV (GPCMV) congenital infection model. (2) Methods: Modified vaccinia virus Ankara (MVA) vaccines expressing GPCMV glycoproteins were used to immunize GPCMV-seronegative, female Hartley guinea pigs (three-dose series, 3 × 107 pfu/dose). After pregnancy was established, the dams underwent an early third-trimester challenge with salivary gland (SG)-adapted GPCMV. (3) Results: All vaccines elicited GPCMV-specific binding and neutralizing antibodies. Preconception immunization resulted in 19.5-, 4.9-, and 698-fold reductions in maternal DNAemia in MVA-gp75/gL, MVA-gpPC and MVA-gpgB groups, respectively, at day 14, post-SG challenge. Vaccination improved pups’ birth weight and reduced mortality and congenital CMV transmission. In controls, cCMV infection was observed in 100% of pups (mean viral load in all visceral organs, 2.4 × 104 genomes/mg), versus 50% in the gB group (visceral viral load, 9.4 × 102 genomes/mg; p < 0.05). No significant reductions in congenital transmission were noted in the MVA-gp75/gL and MVA-gpPC groups. (4) Conclusions: MVA-vectored gB, gH/gL, and PC vaccines were immunogenic, and protected against maternal DNAemia and pup mortality. These results support the inclusion of multiple glycoprotein complexes in a cCMV vaccine.

AB - (1) Background: A congenital cytomegalovirus (cCMV) vaccine is a major research priority, but the essential glycoprotein target(s) remain unclear. We compared CMV gB (gpgB), gH/gL (gp75/gL), and pentameric complex (gpPC, composed of gH/gL/GP129/GP131/GP133) vaccines in a guinea pig CMV (GPCMV) congenital infection model. (2) Methods: Modified vaccinia virus Ankara (MVA) vaccines expressing GPCMV glycoproteins were used to immunize GPCMV-seronegative, female Hartley guinea pigs (three-dose series, 3 × 107 pfu/dose). After pregnancy was established, the dams underwent an early third-trimester challenge with salivary gland (SG)-adapted GPCMV. (3) Results: All vaccines elicited GPCMV-specific binding and neutralizing antibodies. Preconception immunization resulted in 19.5-, 4.9-, and 698-fold reductions in maternal DNAemia in MVA-gp75/gL, MVA-gpPC and MVA-gpgB groups, respectively, at day 14, post-SG challenge. Vaccination improved pups’ birth weight and reduced mortality and congenital CMV transmission. In controls, cCMV infection was observed in 100% of pups (mean viral load in all visceral organs, 2.4 × 104 genomes/mg), versus 50% in the gB group (visceral viral load, 9.4 × 102 genomes/mg; p < 0.05). No significant reductions in congenital transmission were noted in the MVA-gp75/gL and MVA-gpPC groups. (4) Conclusions: MVA-vectored gB, gH/gL, and PC vaccines were immunogenic, and protected against maternal DNAemia and pup mortality. These results support the inclusion of multiple glycoprotein complexes in a cCMV vaccine.

KW - Congenital cytomegalovirus infection

KW - Cytomegalovirus glycoproteins

KW - Cytomegalovirus vaccine

KW - Guinea pig cytomegalovirus

KW - Pentameric complex (PC)

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SN - 2076-393X

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JO - Vaccines

JF - Vaccines

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ER -

MVA-vectored pentameric complex (PC) and gB vaccines improve pregnancy outcome after guinea pig CMV challenge, but only gB vaccine reduces vertical transmission

Abstract

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Keywords

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