Pharmacological management of human respiratory syncytial virus infection

ABSTRACT

Introduction

Human respiratory syncytial virus (hRSV) is the primary viral cause of respiratory diseases, leading to bronchiolitis and pneumonia in vulnerable populations. The only current treatment against this virus is palliative, and no efficient and specific vaccine against this pathogen is available.

Areas covered

The authors describe the disease symptoms caused by hRSV, the economic and social impact of this infection worldwide, and how this infection can be modulated using pharmacological treatments, preventing and limiting its dissemination. The authors discuss the use of antibodies as prophylactic tools -such as palivizumab- and the use of nonspecific drugs to decrease the symptoms associated with the infection -such as bronchodilators, corticoids, and antivirals. They also discuss current vaccine candidates, new prophylactic treatments, and new antivirals options, which are currently being tested.

Expert opinion

Today, many researchers are focused on developing different strategies to modulate the symptoms induced by hRSV. However, to achieve this, understanding how current treatments are working and their shortcomings needs to be further elucidated.

KEYWORDS:

• Human respiratory syncytial virus
• virus infection
• prophylactic drugs
• pharmacologic treatment

Article highlights

• hRSV generates an inadequate non-protective immunology memory, causing frequent reinfections in children, leading to hospitalization due to bronchiolitis, pneumonia, and -in critical cases- neurological manifestations.

• Palivizumab is a monoclonal antibody against F protein of hRSV, and is the only FDA-approved prophylactic approach.

• Bronchodilators and corticosteroids are common pharmacological measures used to mitigate disease symptoms, and ribavirin is the only antiviral currently approved by the FDA used to palliate hRSV disease.

• The development of novel therapies to treat hRSV have focused on the development of antibodies and antivirals that could modulate the essential mechanisms for the replicative and infective cycle, the survival, or the latency processes of this virus.

• Development of hRSV vaccines prototypes are promising approaches to treat hRSV. Among these are the generation of genetically modified virus, subunit vaccines, Virus like-particles (VLPs), and recombinant live-attenuated vaccines.

• rBCG-N-hRSV is a live-attenuated vaccine that promotes a robust immune cellular and humoral response in humans as shown recently in a phase I clinical trial.

This box summarizes key points contained in the article.

Declaration of interest

JA Soto has received Comisión Nacional de Investigación Científica y Tecnológica/The National Fund for Scientific and Technological Development (CONICYT/FONDECYT) POSTDOCTORADO grant No. 3,190,590 while NMS Galvez is supported by CONICYT grants No. 21,190,183. K Bomhwald is supported by CONICYT/FONDECYT POSTDOCTORADO grant No. 3,180,570. AM Kalergis is a Helen C. Levitt Visiting Professor at the Department of Microbiology and Immunology of the University of Iowa. The authors also declare that they have filed a patent application for an anti-N mAb that may be considered as a conflict of interest. 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

One referee declares affiliation with IMV Inc, a company that in its pipeline has a vaccine for RSV, known as DPX-RSV(A). Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Authors’contributions

All authors listed have made substantial, direct, and intellectual contribution 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.

CA: writing original draft

KB: writing original draft

AF: writing original draft

SB: editing and revision

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

Additional information

Funding

This research was funded by FONDECYT 1190830, the Millennium Institute on Immunology and Immunotherapy P09/016-F and COPEC-UC 2019.R.1169. AMK is a Helen C. Levitt visiting professor at the Department of Microbiology and Immunology of the University of Iowa.