Protection against Congenital CMV Infection Conferred by MVA-Vectored Subunit Vaccines Extends to a Second Pregnancy after Maternal Challenge with a Heterologous, Novel Strain Variant

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

Research output: Contribution to journalArticlepeer-review

Abstract

Maternal reinfection of immune women with novel human cytomegalovirus (HCMV) strains acquired during pregnancy can result in symptomatic congenital CMV (cCMV) infection. Novel animal model strategies are needed to explore vaccine-mediated protections against maternal reinfection. To investigate this in the guinea pig cytomegalovirus (GPCMV) model, a strictly in vivopassaged workpool of a novel strain, the CIDMTR strain (dose, 1107 pfu) was used to infect dams that had been challenged in a previous pregnancy with the 22122 strain, following either shamimmunization (vector only) or vaccination with MVA-vectored gB, gH/gL, or pentameric complex (PC) vaccines. Maternal DNAemia cleared by day 21 in the glycoprotein-vaccinated dams, but not in the sham-immunized dams. Mean pup birth weights were 72.85 10.2, 80.06.9, 81.414.1, and 89.388.4 g in sham-immunized, gB, gH/gL, and PC groups, respectively ( < 0.01 for control v. PC). Pup mortality in the sham-immunized group was 6/12 (50%), but reduced to 3/35 (8.6%) in combined vaccine groups ( = 0.0048). Vertical CIDMTR transmission occurred in 6/12 pups (50%) in the sham-vaccinated group, compared to 2/34 pups (6%) in the vaccine groups ( = 0.002). We conclude that guinea pigs immunized with vectored vaccines expressing 22122 strain-specific glycoproteins are protected after a reinfection with a novel, heterologous clinical isolate (CIDMTR) in a second pregnancy.

Original languageEnglish (US)
Article number2551
JournalViruses
Volume13
Issue number12
DOIs
StatePublished - Dec 2021

Bibliographical note

Funding Information:
Funding: This research was funded by support from NIH HD098866 (MRS), AI114013 (MRS), and HD079918 (MRS). DJD is partially supported by U19AI128913 (Reed), P50CA107399 (Forman) and R01 CA181045 (DJD). 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 NIH.

Publisher Copyright:
© 2022 by the authors.

Keywords

  • CIDTMR strain
  • CMV reinfection
  • CMV vaccine
  • Congenital CMV
  • GO
  • Guinea pig
  • Pentameric complex
  • TAMYC

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