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Updated: Jul 1, 2026
Handling of the Cotton Rat in Studies for the Pre-clinical Evaluation of Oncolytic Viruses
Published on: November 24, 2014
An alphavirus replicon-based human metapneumovirus vaccine is immunogenic and protective in mice and cotton rats
Hoyin Mok1, Sharon J Tollefson, Amy B Podsiad
1Departments of Pediatrics, Vanderbilt University Medical Center, Vanderbilt University, Nashville, Tennessee 37232, USA.
Abstract:
Human metapneumovirus (hMPV) is a recently discovered paramyxovirus that causes upper and lower respiratory tract infections in infants, the elderly, and immunocompromised individuals worldwide. Here, we developed Venezuelan equine encephalitis virus replicon particles (VRPs) encoding hMPV fusion (F) or attachment (G) glycoproteins and evaluated the immunogenicity and protective efficacy of these vaccine candidates in mice and cotton rats. VRPs encoding hMPV F protein, when administered intranasally, induced F-specific virus-neutralizing antibodies in serum and immunoglobulin A (IgA) antibodies in secretions at the respiratory mucosa. Challenge virus replication was reduced significantly in both the upper and lower respiratory tracts following intranasal hMPV challenge in these animals. However, vaccination with hMPV G protein VRPs did not induce neutralizing antibodies or protect animals from hMPV challenge. Close examination of the histopathology of the lungs of VRP-MPV F-vaccinated animals following hMPV challenge revealed no enhancement of inflammation or mucus production. Aberrant cytokine gene expression was not detected in these animals. Together, these results represent an important first step toward the use of VRPs encoding hMPV F proteins as a prophylactic vaccine for hMPV.
Insights
Venezuelan equine encephalitis virus replicon particles (VRPs) encoding the human metapneumovirus (hMPV) F protein induced protective immunity in animal models. This approach shows promise as a novel vaccine strategy against hMPV infections.
Area of Science:
- Virology
- Vaccinology
- Immunology
Background:
- Human metapneumovirus (hMPV) is a significant respiratory pathogen affecting vulnerable populations globally.
- Current prophylactic options for hMPV are limited, necessitating the development of new vaccine strategies.
Purpose of the Study:
- To develop and evaluate Venezuelan equine encephalitis virus replicon particles (VRPs) encoding hMPV fusion (F) or attachment (G) glycoproteins as vaccine candidates.
- To assess the immunogenicity and protective efficacy of these VRP-based vaccines in preclinical animal models.
Main Methods:
- VRPs encoding hMPV F or G glycoproteins were constructed.
- Vaccine candidates were administered intranasally to mice and cotton rats.
- Immunogenicity was assessed by measuring virus-neutralizing antibodies and mucosal IgA.
- Protective efficacy was evaluated through intranasal hMPV challenge, monitoring viral replication and lung pathology.
Main Results:
- Intranasal administration of VRPs encoding the hMPV F protein elicited F-specific neutralizing antibodies in serum and IgA in respiratory secretions.
- Vaccination with hMPV F protein VRPs significantly reduced viral replication in both upper and lower respiratory tracts post-challenge.
- VRPs encoding the hMPV G protein did not induce protective immunity or neutralizing antibodies.
- No enhanced inflammation or mucus production was observed in the lungs of F-VRP vaccinated animals after challenge.
Conclusions:
- VRPs encoding the hMPV F protein are immunogenic and confer significant protection against hMPV challenge in preclinical models.
- This study provides a strong foundation for developing VRP-based vaccines targeting the hMPV F protein for prophylactic use.
