Membrane association of a model CD4+ T-cell vaccine antigen confers enhanced yet incomplete protection against murid herpesvirus-4 infection

Immunol Cell Biol. 2020 Apr;98(4):332-343. doi: 10.1111/imcb.12319. Epub 2020 Feb 29.


Vaccination against γ-herpesviruses has proved difficult. CD4+ T cells are essential to contain infection, but how best to prime them and whether this can reduce viral loads remain unclear. To address these questions, we used ovalbumin (OVA) as a model antigen, delivering it with murine cytomegalovirus (MCMV) to protect mice against OVA-expressing murine herpesvirus-4 (MuHV-4). Membrane-associated OVA (mOVA) was more effective than soluble OVA, both to prime CD4+ T cells and as an effector target. It was also a better target than an OVA epitope limited to infected cells, suggesting that protective CD4+ T cells recognize infected cell debris rather than infected cells themselves. While MCMV-mOVA protected acutely against MuHV-4-mOVA, long-term protection was incomplete, even when OVA-specific CD8+ T cells and B cells were also primed. Thus, even optimized single-target vaccines may poorly reduce long-term γ-herpesvirus infections.

Keywords: CD4+ T cell; gamma-herpesvirus; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Herpesviridae Infections / immunology*
  • Herpesviridae Infections / prevention & control
  • Herpesvirus Vaccines / immunology*
  • Immunogenicity, Vaccine / immunology*
  • Membrane Proteins / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • NIH 3T3 Cells
  • Ovalbumin / immunology*
  • Rhadinovirus / genetics
  • Rhadinovirus / immunology*
  • Time Factors
  • Vaccination


  • Herpesvirus Vaccines
  • Membrane Proteins
  • Ovalbumin