Lack of neonatal Fc receptor does not diminish the efficacy of the HSV-1 0ΔNLS vaccine against ocular HSV-1 challenge

Vaccine. 2021 Apr 28;39(18):2526-2536. doi: 10.1016/j.vaccine.2021.03.075. Epub 2021 Apr 1.


The neonatal Fc receptor (FcRn) is constitutively expressed in the cornea and is up-regulated in response to herpes simplex virus type 1 (HSV-1). Previously, we found targeting cornea FcRn expression by small interfering RNA-mediated knockdown reduced the local efficacy of HSV-1 0ΔNLS vaccinated C57BL/6 mice against ocular challenge with HSV-1. The current study was undertaken to evaluate the HSV-1 0ΔNLS vaccine efficacy in FcRn deficient (FcRn KO) mice challenged with HSV-1. Whereas there was little neutralizing antibody detected in the serum of HSV-1 0ΔNLS vaccinated FcRn KO mice, these mice exhibited the same degree of protection against ocular challenge with HSV-1 as wild type (WT) C57BL/6 mice as measured by cumulative survival, infectious virus shed or retained in tissue, and corneal pathology including opacity and neovascularization. Mock-vaccinated FcRn KO mice were found to be more sensitive to ocular HSV-1 infection compared to mock-vaccinated (WT) mice in terms of cumulative survival and virus shedding. In addition, the FcRn KO mice generated significantly fewer effector (CD3+CD44+CD62L-) and central (CD3+CD44+CD62L+) memory CD8+ T cells compared to the WT mice 7 days post infection. Collectively, mock-vaccinated FcRn KO mice are susceptible to ocular HSV-1 infection but HSV-1 0ΔNLS vaccinated FcRn KO mice are resistant suggesting that in addition to the FcRn, other pathways are involved in mediating the protective effect of the HSV-1 0ΔNLS vaccine against subsequent HSV-1 challenge.

Keywords: Cornea; Herpes simplex virus type 1; Neonatal Fc receptor; Neovascularization; Vaccine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes
  • Eye Diseases / virology*
  • Herpes Simplex / prevention & control*
  • Herpes Simplex Virus Vaccines*
  • Herpesvirus 1, Human
  • Histocompatibility Antigens Class I
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Fc / genetics*


  • Herpes Simplex Virus Vaccines
  • Histocompatibility Antigens Class I
  • Receptors, Fc
  • Fc receptor, neonatal