Profile of respiratory syncytial virus prefusogenic fusion protein nanoparticle vaccine

ABSTRACT

Introduction

Respiratory Syncytial Virus (RSV) is a leading cause of acute lower respiratory infections worldwide. The RSV fusion (F) glycoprotein is a major focus of vaccine development. Despite over 60 years of research, there is no licensed vaccine for RSV.

Areas covered

The primary focus of this review is a novel RSV-F recombinant nanoparticle vaccine from Novavax utilizing the F protein, a conserved and immunodominant surface glycoprotein. This RSV F recombinant nanoparticle vaccine adsorbed to 0.4 mg of aluminum phosphate was ultimately administered by a single intramuscular injection during the third trimester of pregnancy in an effort to induce passive immunity in newborns. Its mechanism, performance in clinical trials, and place in RSV vaccine history are discussed.

Expert opinion

The vaccine was safe and well tolerated in pregnant women and the results suggest potential benefits with respect to other medically relevant end-point events involving RSV-associated respiratory and all-cause disease in infants. However, the RSV-F recombinant nanoparticle vaccine did not meet the pre-specified primary success criteria for efficacy against RSV-associated, medically significant lower respiratory tract infection in infants up to 90 days of life. The potential benefits to infants from maternal immunization and excellent safety profile warrant further confirmatory studies.

GRAPHICAL ABSTRACT

KEYWORDS:

• Respiratory syncytial virus
• vaccine
• maternal immunization
• nanoparticle
• medically significant lower respiratory tract infection
• transplacental antibody

Article highlights

• A single dose of 120 µg + 0.4 mg aluminum phosphate adjuvant was safe and well tolerated in pregnant women and their infants, with no associated adverse events occurring during pregnancy or at parturition.

• The RSV-F recombinant nanoparticle vaccine stimulates high levels of RSV-specific antibodies in the blood of the vaccinated pregnant women. These antibodies are neutralizing and compete with monoclonal antibodies for a broad number of known epitopes on the pre-fusion and post-fusion conformations of the F protein.

• A first of its kind phase III maternal immunization trial to protect infants against severe RSV disease was conducted. VE against RSV-MS-LRTI was 39.4% (97.52 CI: −1.0, 63.7%; p=0.0278) in infants 0 – 90 days of age, which did not meet the prespecified primary endpoint. VE for secondary endpoints RSV-LRTI with severe hypoxemia was 48.3% (95% CI, −8.2 to 75.3), and the reduction of hospitalization for RSV-associated lower respiratory tract infection was 44.4% (95% CI 19.6 to 61.5).

• Exploratory analysis showed reduction of all-cause pneumonia through 364 days of life by approximately 50% indicating maternal immunization is a viable strategy for reducing the global burden of RSV and the novel RSV F nanoparticle vaccine warrants further confirmatory studies.

Declaration of interest

PA Piedra received grant from Novavax and served a scientific advisor in their RSV vaccine program. 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.

Additional information

Funding

This paper was not funded.