On the Precipice of the World's First RSV Vaccine: What's Taking so Long?

There’s a different respiratory virus making headlines this season.

Respiratory syncytial virus (RSV) is a common respiratory virus that typically causes mild, cold-like symptoms. While most people recover within 2 weeks, infants and older adults are susceptible to the worst of the infection.

The past couple of years, COVID-19-inspired preventative measures had the added benefit of reducing the incidence of other viruses like influenza and RSV. Now that practices like masking and social distancing are falling out of favor, we are seeing an increase in seasonal respiratory viruses.

RSV spiked early and violently this year, with infants under 6 months and adults over 65 years experiencing severe and fatal infection. “We’ve actually had summer outbreaks of RSV in the last couple of years, which is very, very unusual” said Tina Q. Tan, MD, FAAP, FIDSA, FPIDS, a professor of pediatrics at Northwestern University’s Feinberg School of Medicine, medical director of the International Patient Services Program (IPS); co-director of the Pediatric Travel Medicine Clinic; and director of the International Adoptee Clinic at Ann & Robert H. Lurie Children’s Hospital of Chicago.

This year’s high rate of severe RSV infections is unprecedented, even in years before the public actively worked to lower disease transmission. The Centers for Disease Control and Prevention (CDC) reported RSV hospitalizations for children 0-4 years of age peaked at 237.2 per 100000 people, while hospitalizations in adults older than 65 years peaked at 17.6 per 100000 people.

Overall hospitalizations this season peaked at 19.5 per 100000 people. For reference, the previous high was a peak of 8.8 overall hospitalizations per 100000 people, recorded during the 2019-2020 RSV season.

“It’s just been massively out of control this year…People are acutely feeling it now due to the intensity of the peak,” said Iona M. Munjal, MD, director of clinical research and development at Pfizer.

Munjal explained that most children are exposed to RSV by the age of 5, and easily clear the virus. Now, as schools and daycares begin to open post-pandemic, large numbers of young children are experiencing severe RSV after being exposed to the virus for the first time.

RSV was first formally identified in the 1950s. Since then, Munjal said, there have not been effective solutions. “There is a single monoclonal that you give to infants that is very, very costly, and it requires a monthly injection, so it’s only given to high-risk infants.”

There is another extended duration monoclonal antibody completing phase 3 trials, which Tan called a “very promising development.” This monoclonal would be for healthy preterm and term infants, greater than 29 weeks gestation. If authorized, infants would receive a single dose of this monoclonal antibody prior to RSV season, and due to its extended duration, 1 dose would last the entire RSV season.

Of course, a high incidence rate of RSV does not mean other respiratory viruses have disappeared. Quite the opposite; fears of a confluence of RSV, influenza, and COVID-19, which some are calling a “tridemic,” are very real. “In addition to those 3 viruses,” said Tan, “there are other respiratory tract viruses that are also circulating that play into this mix.”

Unlike COVID-19 and flu, there is no approved vaccination to combat RSV. However, this could be about to change.

The COVID-19 pandemic demonstrated the rapidity with which a vaccine can be developed when there is a drastic unmet need. RSV has been circulating for decades longer than COVID-19, so why has it taken so long for us to get this close to the first authorized RSV vaccine?

Munjal says that the RSV virus is particularly elusive. “What's really interesting about RSV is that it comes in, it changes its shape, and then it attaches to the human host cell,” she explained. “This shape change was something we didn’t know at first.”

Tan reiterated the challenging structure of the RSV organism. She said there are a few RSV vaccines that have successfully completed phase 3 clinical trials and are going to be submitted to the US Food and Drug Administration (FDA) for licensure.

Pfizer’s bivalent RSV prefusion vaccine candidate, RSVpreF or PF-06928316, accounts for the virus’s shape change. “We target the prefusion form of the virus,” said Munjal. The vaccine candidate is administered to pregnant people to help protect their infants from RSV after birth.

After sharing positive phase 3 data from the RSVpreF investigational vaccine, Pfizer announced plans to submit a Biologics License Application (BLA) to the FDA by the end of 2022.

Munjal says the fact that we are on the precipice of the first approved RSV vaccine makes it easier to talk about this season’s high incidence. “I think that when you have solutions, people are more able to talk to the problem,” Munjal commented, “because otherwise, it's frustrating.”

Tan specifically noted that the Pfizer maternal vaccine is the most promising. “The pregnant woman gets a dose of this vaccine,” she said, “and data from the phase 3 trials show that it is 82% effective preventing RSV lower tract disease in infants during the first three months of life. So it is very, very promising.”

There are other RSV vaccines on the horizon, albeit not as far along as the Pfizer maternal vaccine. “There are some RSV vaccines that are still in very early clinical trials,” said Tan. “These are intranasal RSV, vaccines that will be used in children somewhere between 6 months and 24 months of age.”

When asked why Pfizer is focused on maternal vaccination, Munjal cited its safety and efficacy. “I'm a pediatrician; if I could prevent half of the babies coming into the hospital, I would,” said Munjal. “82% [efficacy] for me is a really, really amazing achievement for the vaccine. And we're very excited.”

Munjal also noted maternal vaccination ensures high levels of antibodies are passed to infants: “We found that in some cases, moms were passing more antibodies to the baby than they kept to themselves…So relatively, they're transferring a very, very high load of antibodies to the baby.”

Respiratory viruses can be especially dangerous for pregnant people and their infants. Unfortunately, there has been an uptick in vaccine misinformation during the COVID-19 pandemic that could impact vaccinations among the most vulnerable populations.

“I think one of the biggest misconceptions is…that that moms aren't into taking vaccines,” said Munjal. “We've shown that in countries in which vaccines can be widely available, the uptick in the pregnant population is really quite good.”

Munjal emphasized that although US is experiencing a high rate of RSV in infants, these infections can be even more fatal in other nations. Therefore, the Pfizer RSV vaccine trials included a number of other countries. “Outside of the US, we have 17 other countries… we thought it was equally important to gain data in those countries.”

As previously noted, older adults are also disproportionately likely to experience severe or fatal RSV disease progression. Munjal said that Pfizer plans to submit a Biologics License Application (BLA) for both maternal and older adult populations. “The same dose that we give to pregnant women, it showed efficacy this year in older adults.”

The most common symptoms of RSV are congestion or runny nose, coughing, loss of appetite, fever or chills, sneezing, sore throat, and wheezing. While these do overlap with COVID-19 and flu symptoms, sneezing and wheezing specifically are unique to RSV.

The best way to know if one is experiencing RSV, Tan says, is to get tested, especially if the infected person is a young child or older adult. “If you have someone presenting to you that is sick enough to seek medical care, you really need to test them to determine which one of these viruses, or ones of these viruses.” Coinfection can occur, and knowing how to treat these patients can be lifesaving.

RSV is not new, but while in the past people experiencing the virus would settle for simply calling it “a cold,” Munjal says that the severity of the COVID-19 pandemic has heightened our attention to respiratory viruses.

“I think from a pediatric perspective, I'm always struck by how prevalent the virus is,” said Munjal, noting, “almost 100% of kids have this by age 2, so you don’t get away from RSV. It’s so prevalent and so contagious that almost everyone is exposed.”

Munjal also explained why RSV is so much more deadly for infants and young children. RSV causes a large volume of fluid to build up in the lungs. While this is only mildly dangerous for adults, who have a large breathing tube, “babies are breathing through a breathing tube that's the size of a straw, and it completely fills up with fluid, and you see them struggling to breathe,” said Munjal.

“Since the 1960s, you say, ‘Oh I know your baby has RSV, and there’s nothing I can do,’” explained Munjal. An RSV vaccine would certainly be beneficial on a global level, by significantly reducing the strain on hospital resources. But Munjal noted a vaccine is also about “That really, really impactful, patient-by-patient experience…That’s the joy in this vaccine, you can finally say, ‘I have something to offer.’”

Keep up with the latest developments in RSV, vaccines, and RSV vaccines on ContagionLive.