Inactivated Rabies Virus Vectored MERS-Coronavirus Vaccine Induces Protective Immunity in Mice, Camels, and Alpacas

Front Immunol. 2022 Jan 31:13:823949. doi: 10.3389/fimmu.2022.823949. eCollection 2022.

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is an emergent coronavirus that has caused frequent zoonotic events through camel-to-human spillover. An effective camelid vaccination strategy is probably the best way to reduce human exposure risk. Here, we constructed and evaluated an inactivated rabies virus-vectored MERS-CoV vaccine in mice, camels, and alpacas. Potent antigen-specific antibody and CD8+ T-cell responses were generated in mice; moreover, the vaccination reduced viral replication and accelerated virus clearance in MERS-CoV-infected mice. Besides, protective antibody responses against both MERS-CoV and rabies virus were induced in camels and alpacas. Satisfyingly, the immune sera showed broad cross-neutralizing activity against the three main MERS-CoV clades. For further characterization of the antibody response induced in camelids, MERS-CoV-specific variable domains of heavy-chain-only antibody (VHHs) were isolated from immunized alpacas and showed potent prophylactic and therapeutic efficacies in the Ad5-hDPP4-transduced mouse model. These results highlight the inactivated rabies virus-vectored MERS-CoV vaccine as a promising camelid candidate vaccine.

Keywords: MERS-CoV; alpaca; camel; mice; rabies virus vector; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • CD8-Positive T-Lymphocytes / immunology
  • Camelids, New World / immunology
  • Camelids, New World / virology*
  • Camelus / immunology
  • Camelus / virology*
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Coronavirus Infections / immunology
  • Coronavirus Infections / prevention & control
  • Coronavirus Infections / veterinary*
  • Cricetinae
  • Female
  • Genetic Vectors / genetics
  • Genetic Vectors / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle East Respiratory Syndrome Coronavirus / immunology*
  • Rabies virus / genetics
  • Rabies virus / immunology
  • Vaccination
  • Vaccines, Synthetic / immunology
  • Vero Cells
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Vaccines, Synthetic
  • Viral Vaccines