Evaluation of the immunogenicity of an mRNA vectored Nipah virus vaccine candidate in pigs

Front Immunol. 2024 Apr 25:15:1384417. doi: 10.3389/fimmu.2024.1384417. eCollection 2024.

Abstract

Nipah virus (NiV) poses a significant threat to human and livestock populations across South and Southeast Asia. Vaccines are required to reduce the risk and impact of spillover infection events. Pigs can act as an intermediate amplifying host for NiV and, separately, provide a preclinical model for evaluating human vaccine candidate immunogenicity. The aim of this study was therefore to evaluate the immunogenicity of an mRNA vectored NiV vaccine candidate in pigs. Pigs were immunized twice with 100 μg nucleoside-modified mRNA vaccine encoding soluble G glycoprotein from the Malaysia strain of NiV, formulated in lipid nanoparticles. Potent antigen-binding and virus neutralizing antibodies were detected in serum following the booster immunization. Antibody responses effectively neutralized both the Malaysia and Bangladesh strains of NiV but showed limited neutralization of the related (about 80% amino acid sequence identity for G) Hendra virus. Antibodies were also capable of neutralizing NiV glycoprotein mediated cell-cell fusion. NiV G-specific T cell cytokine responses were also measurable following the booster immunization with evidence for induction of both CD4 and CD8 T cell responses. These data support the further evaluation of mRNA vectored NiV G as a vaccine for both pigs and humans.

Keywords: Nipah virus; immunogenicity; mRNA; pig; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing* / blood
  • Antibodies, Neutralizing* / immunology
  • Antibodies, Viral* / blood
  • Antibodies, Viral* / immunology
  • Cytokines / immunology
  • Henipavirus Infections* / immunology
  • Henipavirus Infections* / prevention & control
  • Immunization, Secondary
  • Immunogenicity, Vaccine
  • Liposomes
  • Nanoparticles
  • Nipah Virus* / genetics
  • Nipah Virus* / immunology
  • RNA, Messenger / genetics
  • RNA, Messenger / immunology
  • Swine
  • Swine Diseases / immunology
  • Swine Diseases / prevention & control
  • Swine Diseases / virology
  • Vaccines, Synthetic / immunology
  • Viral Vaccines* / administration & dosage
  • Viral Vaccines* / immunology

Substances

  • Antibodies, Neutralizing
  • Viral Vaccines
  • Antibodies, Viral
  • RNA, Messenger
  • Lipid Nanoparticles
  • Cytokines
  • Vaccines, Synthetic
  • Liposomes

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by the VetBioNet project, European Union Horizon 2020 research and innovation program; and the UK Department for Health and Social Care (SBRI Vaccines for Global Epidemics—Clinical; Contract 971555 ‘A Nipah vaccine to eliminate porcine reservoirs and safeguard human health’). The authors would like to acknowledge the Pirbright Flow Cytometry facility and support through the UKRI Biotechnology and Biological Sciences Research Council (BBSRC) Institute Strategic Program and Core Capability Grants to The Pirbright Institute (BBS/E/I/00007030, BBS/E/I/00007031, BBS/E/I/00007038 and BBS/E/I/00007039). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. LM was registered in the EMJMD LIVE (Erasmus+ Mundus Joint Master’s degree Leading International Vaccinology Education), co-funded by the Education, Audiovisual and Culture Executive Agency (EACEA) of the European Commission and received a scholarship from the EACEA. SG is a Jenner Institute Investigator.