Technically Speaking: Treating and Preventing RSV

Can you name an RNA virus that is a common cause of hospitalization in children in the first year of life as well as immune-compromised people and frail, elderly people, particularly those with cardiopulmonary comorbidities?

• Hint #1: This virus is spread by direct or close contact with contaminated secretions (e.g., from exposure to large particle droplets, typically at distances of < 6 feet) or by touching one’s own face after touching contaminated surfaces.
• Hint #2: There is no vaccine licensed or authorized to prevent infection at this time.

If you said respiratory syncytial virus (RSV), you are correct. In older children, RSV infections most often present as a cold that lasts one to two weeks with symptoms that typically include runny nose, cough, fever, wheezing and decreased appetite. In the first six months of life, symptoms may also include poor feeding, lethargy and/or apnea (breathing slows or stops). The Centers for Disease Control and Prevention (CDC) estimates that 1% to 2% of all children will be hospitalized with a lower respiratory tract infection caused by RSV in the first six months of life. We are fortunate that RSV isn’t even more virulent because almost all children are infected with RSV at least once by 24 months of age.

Due to precautions related to the COVID-19 pandemic during the fall and winter 2020, fewer children were infected with RSV and, therefore, fewer developed immunity. It is hypothesized that this may have contributed to the early arrival of RSV in the spring of 2021 rather than in the fall or winter, which is more typical.

In addition to the large numbers of children that need care for RSV, significant numbers of elderly people are also negatively impacted. In fact, the CDC estimates that each year in the U.S., about 177,000 older adults are hospitalized and about 14,000 die from RSV infections.

The current recommendations on how to prevent the spread of RSV will sound familiar:

• Wash your hands often.
• Keep your hands off your face.
• Avoid close contact with sick people.
• Cover your coughs and sneezes.
• Clean and disinfect surfaces.
• Stay home when you are sick.

Passive immunization

While a monoclonal antibody (palivizumab) is available to prevent severe RSV disease, currently, it is the only licensed intervention available and it is recommended only for particular subgroups of infants (see the American Academy of Pediatrics recommendations for more details). Unfortunately, palivizumab has a short half-life, so it needs to be given to qualifying patients every 28-30 days throughout RSV season.

A new passive immunization, nirsevimab (from Sanofi), is a recombinant, human monoclonal antibody with an extended half-life (85–117 days). Because of its staying power and highly potent neutralizing activity against RSV, one dose is expected to be protective for at least five months, the duration of a typical RSV season. In addition to trials in preterm infants, nirsevimab is being evaluated in a phase 3 trial that includes healthy late-preterm and term infants.

Active immunization

Currently, an RSV vaccine is not available, but there has been some promising news. In a recent article about the future of RSV treatment, Domachowske and colleagues (2021) highlighted the fact that 17 investigational RSV vaccines are in clinical development including live-attenuated, vector-based, particle-based and subunit vaccines.

On Nov. 18, 2021, Moderna announced that the first participant had been enrolled in the phase 2 trial of their mRNA-based RSV candidate vaccine, which uses the same lipid nanoparticle as their COVID-19 vaccine.

The only RSV vaccine in phase 3 trials is ResVax (from Novavax), a recombinant protein nanoparticle-based vaccine designed to be given between 28 and 36 weeks of pregnancy. As with the pertussis vaccine, immunizing pregnant individuals aims to increase maternal antibody levels that pass to the fetus through the placenta prior to birth in order to provide protection during infancy. Unfortunately, during clinical trials, ResVax did not meet its primary endpoint of preventing lower respiratory tract infections caused by RSV in infants, although it did reduce hospitalizations 44% among infants born to vaccinated mothers. Disappointingly, a formulation of ResVax designed for use in the elderly also failed to meet the pre-specified primary or secondary efficacy objectives in clinical trials.

After the stunning success of the COVID-19 vaccine, it is frustrating to wait for immunizations coming through the pipeline at the traditional pace. But wait we must. Unfortunately, in the meantime, infants and seniors with severe RSV are the ones who are literally waiting with bated breath.