A Pan-Pneumovirus vaccine based on immunodominant epitopes of the fusion protein.
Aged
Animals
Antibodies, Neutralizing
Antibodies, Viral
Child
Epitopes
Humans
Immunodominant Epitopes
/ genetics
Metapneumovirus
/ genetics
Mice
Recombinant Proteins
Respiratory Syncytial Virus Vaccines
Respiratory Syncytial Virus, Human
/ genetics
Viral Fusion Proteins
/ genetics
Viral Vaccines
/ genetics
RSV (respiratory syncytial virus)
epitope
fusion protein
human metapneumovirus (hMPV)
neutralizing antibodies
structure-based vaccine design
vaccine
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2022
2022
Historique:
received:
20
05
2022
accepted:
14
07
2022
entrez:
25
8
2022
pubmed:
26
8
2022
medline:
27
8
2022
Statut:
epublish
Résumé
Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are two leading causes of severe respiratory infections in children, the elderly, and immunocompromised patients. The fusion (F) protein is the major target of neutralizing antibodies. Recent developments in stabilizing the pre-fusion conformation of the F proteins, and identifying immunodominant epitopes that elicit potent neutralizing antibodies have led to the testing of numerous pre-fusion RSV F-based vaccines in clinical trials. We designed and tested the immunogenicity and protective efficacy of a chimeric fusion protein that contains immunodominant epitopes of RSV F and hMPV F (RHMS-1). RHMS-1 has several advantages over vaccination with pre-fusion RSV F or hMPV F, including a focus on recalling B cells to the most important protective epitopes and the ability to induce protection against two viruses with a single antigen. RHMS-1 was generated as a trimeric recombinant protein, and analysis by negative-stain electron microscopy demonstrated the protein resembles the pre-fusion conformation. Probing of RHMS-1 antigenicity using a panel of RSV and hMPV F-specific monoclonal antibodies (mAbs) revealed the protein retains features of both viruses, including the pre-fusion site Ø epitope of RSV F. Mice immunized with RHMS-1 generated neutralizing antibodies to both viruses and were completely protected from RSV or hMPV challenge. Overall, this study demonstrates protection against two viruses with a single antigen and supports testing of RHMS-1 in additional pre-clinical animal models.
Identifiants
pubmed: 36003370
doi: 10.3389/fimmu.2022.941865
pmc: PMC9393700
doi:
Substances chimiques
Antibodies, Neutralizing
0
Antibodies, Viral
0
Epitopes
0
Immunodominant Epitopes
0
Recombinant Proteins
0
Respiratory Syncytial Virus Vaccines
0
Viral Fusion Proteins
0
Viral Vaccines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
941865Subventions
Organisme : NIAID NIH HHS
ID : R01 AI143865
Pays : United States
Organisme : NIH HHS
ID : K01 OD026569
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM129325
Pays : United States
Informations de copyright
Copyright © 2022 Huang, Miller and Mousa.
Déclaration de conflit d'intérêts
JH and JJM are listed as inventors on a provisional patent application describing the vaccine candidate. The remaining author declarers that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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