From animal studies into clinical trials: the relevance of animal models to develop vaccines and therapies to reduce disease severity and prevent hRSV infection

ABSTRACT

Introduction

Human respiratory syncytial virus (hRSV) is an important cause of lower respiratory tract infections in the pediatric and the geriatric population worldwide. There is a substantial economic burden resulting from hRSV disease during winter. Although no vaccines have been approved for human use, prophylactic therapies are available for high-risk populations. Choosing the proper animal models to evaluate different vaccine prototypes or pharmacological treatments is essential for developing efficient therapies against hRSV.

Areas covered

This article describes the relevance of using different animal models to evaluate the effect of antiviral drugs, pharmacological molecules, vaccine prototypes, and antibodies in the protection against hRSV. The animal models covered are rodents, mustelids, bovines, and nonhuman primates. Animals included were chosen based on the available literature and their role in the development of the drugs discussed in this manuscript.

Expert opinion

Choosing the correct animal model is critical for exploring and testing treatments that could decrease the impact of hRSV in high-risk populations. Mice will continue to be the most used preclinical model to evaluate this. However, researchers must also explore the use of other models such as nonhuman primates, as they are more similar to humans, prior to escalating into clinical trials.

KEYWORDS:

• Human respiratory syncytial virus
• animal models
• vaccines
• therapies

Article highlights

• Animal models are used for the evaluation of vaccines and therapies against hRSV.

• Advantages and limitations of animal models for studying vaccines and therapies against hRSV.

• Description of the most recent vaccines and therapies evaluated in clinical phases.

• The immune response induced upon infection with hRSV.

• Description of innate immunity in different animal models.

Declaration of interest

The authors declare the following possible conflict of interest: ‘Monoclonal Antibody specific against the antigen N of the Human Respiratory Syncytial Virus (VRSH), useful for the treatment of infection, its detection and diagnosis.PCT/CL2018/050079, date of presentation September 2018.’ In addition, the following patents associated with vaccines are declared: ‘Immunogenic formulation that comprises a recombinant attenuated Mycobacterium strain, preferably a recombinant Calmette-Guérin Bacillus (BCG) strain, which expresses at least one protein or immunogenic fragment of the respiratory syncytial virus (RSV), in a pharmaceutically acceptable saline solution and use thereof to prepare vaccines against RSV.’ PCT (ID PCT/US2008/076682), filled to PCT on September 17^th, 2008.The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Authors’ contributions

All authors listed have made substantial, direct, and intellectual contributions to the work and approved it for publication.

JS : conceptualization, writing original draft, review, editing and revision.

NG : writing original draft, review, editing and revision.

DR : writing original draft, review.

FD : writing original draft, review.

SB : editing and revision.

CR : editing and revision.

AK : conceptualization, revision of original draft, editing and revision of final version.

Additional information

Funding

This work was supported by funding from the Millennium Institute on Immunology and Immunotherapy ANID ACE 210015 (CN09_016 / ICN 2021_045; former P09/016-F, AMK and SMB); CORFO grant #13CTI-21526/P4 and P5; CONICYT/FONDECYT grants #3190590 (JAS); #1190830 (AMK); # 1191300 (CAR); PAI SA77210051 (JAS); CONICYT scholarship #21190183 (NMSG) and #21170620 (FED); CONICYT scholarship: # 21221472 (DBR); and Biomedical Research Consortium CTU06 (AMK). This work was also supported by the Regional Government of Antofagasta through the Innovation Fund for Competitiveness FICR 2017 (BIP Code: 30488811-0). AMK is a Helen C. Levitt Visiting Professor at the Department of Microbiology and Immunology of the University of Iowa.