What to know about RSV vaccine candidates and monoclonal antibodies

Story at a glance

• RSV is surging around the country after two seasons of low respiratory illnesses because of restrictions and public health measures to combat the coronavirus pandemic.

• There currently are no approved vaccines to prevent severe illness from RSV.

• Pfizer and Meissa have vaccine candidates in the works for pregnant and older people and for infants, respectively.

RSV, which stands for respiratory syncytial virus, is surging in number of cases and hospitalizations in young patients across the country.

RSV can cause severe clinical problems in infants, particularly those under six months of age. It can also cause severe disease in older adults.

“We’re just full up with RSV,” said pediatrician Janet Englund at the Seattle Children’s Hospital.

October 31 was the busiest new patient arrival day in the past 5 years in the Seattle Children’s emergency department, according to a representative of the hospital. Fifty percent of the patients visiting the emergency department had respiratory issues. Approximately 35 percent of those patients tested positive for RSV.

“But that’s really the tip of what you’re seeing,” Englund said. Schoolchildren are getting RSV, but may do not need to go to the hospital. Some cancer patients and patients with obstructive lung disease are getting very, very sick, Englund notes.

The medical community has been looking for ways to prevent severe disease from RSV for the past 50 years, since the virus was identified. But it has faced obstacles in developing a vaccine.

For one, efforts to do so stalled due to safety concerns after clinical trials for a vaccine candidate in 1966 resulted in exacerbated disease in participants who were naturally infected, and there were two deaths. For another, as physician Dawn Nolt, professor of pediatrics in the Division of Infectious Diseases at the Oregon Health & Science University School of Medicine, said in an email to Changing America, it is difficult to make something that is very safe in infants, who are most susceptible to RSV, and that stimulates their “immature immune systems” enough to protect them.

Despite those challenges, however, pharmaceutical companies now have multiple potential vaccines and treatments in development, spurred on by a scientific breakthrough in 2013 regarding a protein in the virus. Pfizer has an RSV vaccine candidate in the pipeline that has been tested in maternal patients and older adults. AstraZeneca and Sanofi are jointly working on a monoclonal antibody treatment that could be given to infants and children to prevent severe disease. Meissa announced initial results from an intranasal vaccine for infants six months to 36 months old. GSK also has a vaccine candidate for older adults.

Here’s what we know about these products and what experts are saying about them in the context of the current RSV surge and future seasons.

The Pfizer RSV vaccine candidate

Pfizer has an RSV vaccine candidate called RSVpreF. It is going through clinical trials in pregnant patients and in older adults.

Maternal immunization, or the administration of a vaccine during pregnancy, is one way to get antibodies to newborns. The parent’s body produces antibodies as an immune reaction to the vaccine and can pass those antibodies to the baby through the placenta. Most adults have been exposed to RSV and have antibodies present. The vaccine boosts antibody response, and doctors can time when it is given to pregnant people so their babies have the highest chance of getting the benefits passively before they are born.

RSVpreF provides protection against severe illness requiring medical attention with an efficacy rate of about 82 percent for infants through their first 90 days of life, according to clinical trial data. Protection seems to linger and wane through the first six months of life.

Englund, who enrolled some participants in the maternal clinical trial, notes that the results suggest the vaccine candidate is both very safe and very effective at preventing disease in the baby in the first months of life.

In older adults, the clinical trial data suggests that the vaccine candidate protects against illness with two or more symptoms about 67 percent of the time, and prevents severe illness about 86 percent of the time.

The AstraZeneca/Sanofi monoclonal antibody

A monoclonal antibody called nirsevimab from AstraZeneca and Sanofi has been submitted to the Food and Drug Administration for approval. The companies are targeting the 2023-24 season to begin launching the product, according to a representative.

Monoclonal antibodies are compounds created to attach to specific parts of a pathogen. They mimic antibodies that our bodies naturally produce by inactivating a pathogen or blocking the parts that help them enter our cells.

“The concept that we are envisioning is that nirsevimab will be given to all infants prior to their first RSV season,” said Jon Heinrichs, who is the global project head for nirsevimab at Sanofi. “And then for the second season and beyond, you could protect with an active immunization,” meaning with a vaccine that stimulates an immune response. Sanofi is also working on an RSV vaccine candidate for children.

Nirsevimab is similar to a monoclonal antibody that has already been approved. Palivizumab, also known as Synagis, is only approved for infants who are considered high risk because they were born preterm or have cardiac disease or respiratory issues before their first RSV season.

The biggest difference is that nirsevimab only needs to be administered once at the beginning of the RSV season, while palivizumab needs to be given monthly and is priced in a way that prevents it from being delivered to all newborns.

This monoclonal antibody from AstraZeneca/Sanofi could be crucial to protect babies born long before the RSV season, making the potential maternal vaccine less useful. It could also be administered to vulnerable children entering their second RSV season.

The Meissa RSV vaccine candidate

Although the data for RSVpreF are promising, it is not meant to be administered to children and infants. A vaccine candidate from Meissa being tested in a phase 1 clinical trial attempts to fill this gap.

Meissa’s vaccine was given intranasally to 6-month olds up to 36-month olds. Early data suggest that it is safe, but later phases of clinical trials will be needed to determine its efficacy.

This vaccine candidate is an “exciting concept,” said Sallie Permar, who is the chair of pediatrics at Weill Cornell Medicine and pediatrician in chief at New York-Presbyterian Komansky Children’s Hospital.

The vaccine contains a live attenuated version of the virus, which is like a weaker version of the virus. “Live attenuated vaccines have historically provided broad and durable protection,” said Martin Moore, co-founder and chief scientific officer of Meissa Vaccines, in a press release.

The vaccine, which is given intranasally, is also simpler to administer than a shot.

Englund said this vaccine looks safe, at least from the preliminary information, and this is important because past vaccine candidates have been seen to cause a fair amount of symptoms like fever, stuffy nose or cough.

What we can learn from this RSV surge

None of the products mentioned here will be ready for this RSV season, but one or more them might be available by next year.

And this year has some lessons to offer. One of which is that the government, health care professionals and the public may have let their guard down because recent seasons of respiratory illness during the coronavirus pandemic have been mild.

“I definitely see that we need to be preventing RSV,” Englund said. “We need to prevent it, not just in the United States, because it is a leading cause of death around the world, and to have just one option, one size fits all is not going to work.”

The maternal vaccination route, for instance, may not be effective for babies born preterm, or before they can get the antibodies through the placenta. “I think the big message is flexibility,” Heinrichs said. “Because this RSV season started early, and it started hard. The only way to do it is to have a product that you can deliver when you start to see that signal appear and you can tune it and it provides rapid protection.” The AstraZeneca/Sanofi monoclonal antibody could fill that role.

There are also other vulnerable populations to consider, like older adults and the immunocompromised. “Persons, regardless of age, with compromised immune systems will have difficulty in handling any infection, including respiratory viruses,” Nolt said. “Availability of RSV vaccines as a prevention measure will be welcomed not only for the very young, but for persons with compromised immune systems.”

How any approved products are used in the future will also depend on availability, the time of year and costs. “We don’t fund children’s health care very well,” Permar said. “We fund it through Medicaid options that don’t reimburse as well as Medicare.”

This leads to pediatric beds being less profitable, which in turn contributed to decreased capacity before this season began, and the health care system is now feeling the tensions of that, Permar continued. “We really have to come to terms with the country that we need a Medicare-like program for all which includes children,” Permar said. “Otherwise, we may not get ourselves out of this rut because while RSV is one of these viruses contributing to this respiratory virus surge, it is certainly not the only virus contributing to it.”

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