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

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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 languageEnglish (US)
Article number182
JournalVaccines
Volume7
Issue number4
DOIs
StatePublished - 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.

Keywords

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

PubMed: MeSH publication types

  • Journal Article

Fingerprint Dive into the research topics of 'MVA-vectored pentameric complex (PC) and gB vaccines improve pregnancy outcome after guinea pig CMV challenge, but only gB vaccine reduces vertical transmission'. Together they form a unique fingerprint.

Cite this