RSV Explained — How Respiratory Syncytial Virus Works

Respiratory syncytial virus (RSV) is the most common cause of infant hospitalization in the United States, according to the Centers for Disease Control and Prevention (CDC), and it hospitalizes an estimated 60,000 to 160,000 adults 65 and older each year. For most healthy people it is a cold lasting a week or two; for a very young baby or an older adult with heart or lung disease it can be serious. After decades of failed attempts, vaccines and antibodies were approved from 2023 onward. This article explains how RSV works, why it resisted prevention, and what the new tools do.

Educational content, not medical advice. Talk to your doctor before changing any medication, treatment, or routine. Information here reflects current research but every person's situation differs.

What RSV actually is

RSV is an enveloped virus with a genome made of a single strand of RNA, about 15,200 bases long, in the genus Orthopneumovirus of the family Pneumoviridae. Its RNA is "negative-sense," meaning the genome is the complement of the message that cells read. The virus must therefore carry its own copying enzyme into the cell, because the cell cannot read the genome directly. For the general rules of how viruses invade and replicate, see How Viruses Work: From Infection to Replication.

Particles are pleomorphic, meaning their shape varies. A Canadian government pathogen safety data sheet describes roughly spherical forms of 100 to 350 nanometers and long filaments about 10 micrometers in length, while a 2021 review in the International Journal of Biological Sciences notes that newly released virions are mostly filamentous. The genome encodes 11 proteins, two of them nonstructural.

Two subtypes, A and B, circulate. They are defined by differences in the attachment protein, and according to the Canadian data sheet there is no difference in severity between them.

Protein	Role	Why it matters
F (fusion)	Drives the viral envelope to merge with a cell membrane and merges infected cells with neighbors	The target of all current vaccines and antibodies
G (attachment)	Binds receptors such as CX3CR1 and heparan sulfate on cells	Varies between subtypes A and B
SH	Small ion-channel protein	Not required for infection in cell culture
NS1 and NS2	Nonstructural; help the virus evade innate immune defenses	Dampen the first line of immune response
N, P, M, M2, L	Package the genome, copy RNA, and build the particle	The copying machinery is inside the particle

The F protein deserves a closer look because the rest of this story turns on it. F is built as a spring-loaded trimer, three copies locked together in a tense, high-energy shape. When it meets a cell, it snaps into a different, more stable shape, and the energy released pulls the viral membrane against the cell membrane until they fuse. The tense shape is called prefusion and the relaxed one postfusion.

Think of a mousetrap. A set trap is the prefusion form: it holds stored energy and looks the way it does for a reason. A sprung trap is the postfusion form: stable, flat, and no longer able to do its job. An antibody that locks onto the set trap can stop it from firing. An antibody to the sprung trap is largely useless, because by then the damage is done. According to the review, the prefusion form is the main target of protective neutralizing antibodies, while the postfusion form elicits a narrower response.

How the virus got its name

RSV was found in an unexpected place. In 1955 and 1956, respiratory illness broke out among chimpanzees at the Walter Reed Army Institute of Research. Morris, Blount, and Savage recovered a virus from a chimpanzee with a cold and named it chimpanzee coryza agent, as reported in a 2025 history in mBio on the discovery of RSV. A lab worker who handled the animals developed an upper respiratory illness and made antibodies to the agent, which showed that the virus could infect people.

In 1957, Robert Chanock, Bernard Roizman, and Ruth Myers at Johns Hopkins isolated two viruses from children with lower respiratory illness and found they were indistinguishable from the chimpanzee agent. Cells infected with it fused into giant multinucleated masses called syncytia, and the name respiratory syncytial virus followed from that observation. Chanock and Laurence Finberg reported that 80 percent of healthy children had neutralizing antibody by age four, which showed that the virus was circulating widely in people. The mBio article notes that sources differ on whether to date the discovery to 1956 or 1957.

How RSV infects the airway

The infection follows a sequence familiar from other respiratory viruses, with a few distinctive steps.

1. Entry. Virus particles reach the nose, mouth, or eyes and attach to cells of the airway lining. The G protein helps with attachment, and the main target cells are respiratory epithelial cells. Ciliated cells, the ones with hair-like projections that sweep mucus, express the receptor CX3CR1, which supports infection.
2. Fusion. The F protein switches from its prefusion to its postfusion shape and joins the viral membrane to the cell membrane. According to the 2021 review, entry can also happen through uptake into the cell followed by fusion inside.
3. Copying. The virus's own polymerase makes messenger RNA and new genomes in the cytoplasm.
4. Syncytia. F protein appearing on the surface of infected cells can fuse them with neighboring cells, forming multinucleated syncytia.
5. Release. New particles assemble and bud from the cell surface.
6. Spread downward. In many people, infection begins in the upper airway and, in about half of cases according to the Canadian data sheet, moves to the lower airway, where it can cause bronchiolitis (inflammation of the smallest airways) or pneumonia.

An important point is that much of the damage does not come from the virus killing cells directly. Inflammatory signaling recruits neutrophils and lymphocytes. Excess mucus, shed cilia and dead epithelial cells, and immune infiltrate together block the small airways, which produces wheezing, as described in the 2021 review. The body's response to the virus does a large share of the harm.

Why small airways matter so much

Picture a drinking straw and a coffee stirrer, both partly filled with debris. The thin one clogs first. Resistance to airflow in a tube rises very steeply as the tube gets narrower, roughly with the fourth power of the radius in the physics of smooth flow, so a small amount of swelling and mucus in an infant's tiny bronchioles can reduce airflow far more than the same amount in an adult's wider airways. For how the lungs move air in the first place, see How Lungs Work: Breathing and Gas Exchange.

An infant's airway also provides little reserve. The CDC's clinical overview notes that very young infants may show irritability, decreased activity, or apnea (pauses in breathing) rather than the cough and runny nose of an older child. Severe disease is most common in very young infants, including healthy babies.

How common and how serious RSV is

The numbers below come from different groups, years, and methods, so they should be read as scale rather than as a precise ranking.

Group	Burden	Source
U.S. infants younger than 6 months	About 2 to 3 percent hospitalized with RSV each year	CDC clinical overview, August 2025
U.S. children younger than 5	About 50,000 to 80,000 hospitalizations and 100 to 300 deaths per year	Immunize.org, reviewed August 2025
U.S. adults 65 and older	About 60,000 to 160,000 hospitalizations and 6,000 to 10,000 deaths per year, possibly an underestimate	Immunize.org, reviewed August 2025
Children younger than 5, worldwide, 2019	33.0 million episodes of lower respiratory infection, 3.6 million hospital admissions, 101,400 deaths attributable to RSV	Li et al., The Lancet, 2022

Two details help in reading these figures. The "2 to 3 percent" figure applies to all infants under six months in a given year, not only to infants who have been infected. And the Lancet estimate of 101,400 deaths covers all children under five: nearly half occurred in infants younger than six months, RSV accounted for about 1 in 50 deaths in children under five and 1 in 28 in children under six months, and more than 97 percent of the deaths were in lower-income settings.

Why infants are vulnerable

Several factors combine. Airways are small, as above. Infants have had little previous exposure and so little immune memory. Antibodies passed from mother to baby protect for only a few months and then fade. Premature birth adds underdeveloped lungs and a smaller transfer of maternal antibody. Most of the risk factors for severe disease in children are about age and immune naivety rather than a flaw in the baby.

Why older adults are vulnerable

For decades RSV in adults was thought to be a minor problem, in part because few adults were tested. Immunize.org notes that limited surveillance means the adult figures may underestimate the true burden. Most adults have mild symptoms that resolve in one to two weeks, but the CDC says RSV can also cause severe disease and can worsen asthma, chronic obstructive pulmonary disease (COPD), and heart failure. The risk rises with age and with chronic heart, lung, or immune conditions.

Virus	Annual U.S. burden, as reported	Notes
RSV, adults 65 and older	60,000 to 160,000 hospitalizations; 6,000 to 10,000 deaths	Surveillance limited; possible underestimate
RSV, children under 5	50,000 to 80,000 hospitalizations; 100 to 300 deaths	Leading cause of infant hospitalization
Influenza, all ages (2010 to 2025)	9.4 million to 51 million illnesses; 120,000 to 710,000 hospitalizations; 6,300 to 52,000 deaths	CDC burden estimates; range reflects year-to-year variation

The influenza row covers all ages and the RSV rows cover specific age groups, so the table should not be read as a direct comparison of the two viruses. The flu is covered in its own article, linked in the reading list at the end, and a different respiratory virus family is described in Rhinovirus and the Common Cold Explained.

How RSV spreads, and why you can catch it again

According to the Canadian pathogen data sheet, RSV spreads mainly through direct contact with infectious secretions, including contaminated surfaces, and through large droplets. Spread through small-particle aerosols is considered less likely. The virus can survive for hours on hard surfaces at room temperature, with reports ranging from about 3 to 30 hours, but only about 20 minutes on skin, and it is sensitive to heat and drying. The incubation period is 2 to 8 days. People are infectious while ill and can shed virus for weeks afterward, and young infants and immunocompromised people can shed for longer.

Immunity after infection is incomplete. Reinfection occurs throughout life, and the data sheet says young children can have several infections in a year. Part of the reason is the virus's high mutation rate: RNA copying lacks proofreading, so RSV changes quickly. The other part is that natural infection does not produce long-lasting protection against reinfection, even though later infections are usually milder.

When RSV circulates

In most of the United States, the CDC says RSV season begins in the fall, peaks in the winter, and ends in the spring. Using a 3 percent test-positivity threshold on 2017 to 2020 data, onset falls between mid-September and November, the peak between November and February, and the end between early February and May. Florida starts earlier and runs longer. The CDC notes that the COVID-19 pandemic disrupted RSV circulation and that recent surveillance suggests a return toward pre-pandemic patterns.

Why the first RSV vaccine made things worse

The story of RSV prevention includes one of the most painful episodes in vaccine history. In 1966, in four U.S. studies, children received an RSV vaccine made by inactivating the virus with formalin (formalin-inactivated RSV, or FI-RSV). According to a review on PubMed Central, the vaccine did not protect. In one study, 80 percent of vaccinated children who became infected with RSV were hospitalized, compared with 5 percent of controls, and two vaccinated children died. The phenomenon was named enhanced respiratory disease.

For years the episode discouraged work on RSV vaccines. Researchers have since proposed several overlapping explanations, and the same review lists them:

• A poor-quality antibody response. The vaccine produced antibody that bound the virus weakly and did not neutralize it. On later infection, the antibody formed immune complexes and activated complement, a set of blood proteins that trigger inflammation, which may have driven lung damage. Complement is covered in Complement System: The Body's Cascade Defense Explained.
• A skewed T-cell response. Helper T cells primed by the vaccine responded to infection with a pattern (Th2) that favors mucus and eosinophils, a type of white blood cell.
• A missing killer T-cell response. The inactivated antigens did not induce cytotoxic T cells, which clear infected cells.
• Altered antigens. Formaldehyde treatment may have modified viral proteins.

No child who already had RSV antibodies before the vaccine developed enhanced disease, and none had it twice, which suggests that pre-existing high-quality antibody protected against the effect. The FDA states that a clear mechanistic understanding of the enhanced disease has not been established, so the list above should be read as leading hypotheses rather than as a settled account. An older shorthand blamed formalin for damaging the shape of the F protein, a widely held hypothesis in the older literature, but the review notes that the role of the prefusion versus postfusion form needs further study.

What the episode did establish is a design rule. Candidate vaccines for infants who have never met RSV must be shown not to produce nonneutralizing antibody or a strongly Th2-skewed response. That caution shaped decades of trials. For how antibodies are built and why shape matters, see Antibody Structure: How the Immune System's Y-Shaped Weapon Works.

The structural breakthrough of 2013

The next step was to learn what a protective antibody actually sees. Neutralizing antibodies bind the F protein in its prefusion shape, but the prefusion shape is unstable and tends to collapse into the postfusion form, so a vaccine made from the protein could end up displaying the wrong one.

In 2013, Jason McLellan, Barney Graham, Peter Kwong, and colleagues published "Structure-based design of a fusion glycoprotein vaccine for respiratory syncytial virus" in Science (volume 342, pages 592 to 598). They focused on antigenic site Ø, a site present only in the prefusion shape that is recognized by potent neutralizing antibodies. By adding cysteine residues, which form a locking disulfide bond, and filling cavities in the protein's core, they held F in the prefusion state. The engineered protein, called DS-Cav1, produced neutralizing antibody levels in mice and macaques that were many times higher than needed to block RSV, according to the paper's summary. A later paper described a second-generation design, DS2.

The method is a general one: use the three-dimensional structure to find where a protein is unstable and lock it in the shape the immune system should learn. The same logic was later applied to the spike protein of coronaviruses. For the immune side of vaccination, see How Vaccines Actually Work: The Immune System Story.

The new tools, one by one

Between 2023 and 2025, the U.S. Food and Drug Administration (FDA) approved three vaccines and two long-acting antibodies. They differ in who they are for and how they work. The efficacy figures below come from different trials with different definitions, so they should not be compared head to head.

Product	Maker	Type	Who it is for	Key trial result
Arexvy	GSK	Protein subunit vaccine with adjuvant	Adults 60 and older at approval (May 3, 2023); later also adults 50 to 59 at increased risk	82.6% against RSV lower respiratory tract disease; 94.1% against severe disease
Abrysvo	Pfizer	Bivalent protein subunit vaccine (subtypes A and B)	Adults 60 and older; pregnant people at 32 to 36 weeks (approved August 21, 2023)	Older adults: 66.7% (two or more symptoms) and 85.7% (three or more). Infants after maternal vaccine: 81.8% against severe disease at 90 days, 69.4% at 180 days
mRESVIA	Moderna	mRNA vaccine encoding prefusion F	Adults 60 and older (approved May 31, 2024)	83.7% in primary analysis; 78.7% in follow-up reflected in the label
Beyfortus (nirsevimab)	Sanofi and AstraZeneca	Long-acting monoclonal antibody	Infants born during or entering their first RSV season; some children into a second season	About 70% (preterm) and 75% (term and late preterm) reduction in medically attended RSV lower respiratory infection over 150 days
Enflonsia (clesrovimab)	Merck	Long-acting monoclonal antibody	Infants born during or entering their first RSV season (approved June 9, 2025)	60.5% reduction in medically attended RSV lower respiratory infection through 5 months; 84.3% reduction in RSV hospitalizations

Sources: FDA announcements for Abrysvo and Beyfortus; reported trial data for Arexvy, mRESVIA, and Enflonsia from the manufacturers and press summaries; Walsh and colleagues, New England Journal of Medicine, 2023, for Abrysvo in older adults.

A note on safety. The FDA required GSK to run a postmarketing study of Guillain-Barré syndrome and acute disseminated encephalomyelitis after cases were reported with Arexvy. For Abrysvo, the FDA's announcement states that preterm births occurred in 5.7 percent of recipients versus 4.7 percent of placebo recipients, that the data could neither confirm nor exclude a causal link, and that the label advises against use before 32 weeks of gestation. These are the kinds of risks that regulators track after approval, and individual decisions belong with a clinician.

What the CDC recommends, as of August 2025

CDC pages dated August 2025 give the following guidance, which may have been updated since.

• Adults. A single dose of RSV vaccine for all adults 75 and older and for adults 50 to 74 who are at increased risk of severe disease.
• Infants. Either a maternal vaccine (Abrysvo) at 32 to 36 weeks of pregnancy or a long-acting infant antibody (nirsevimab or clesrovimab) after birth. Infants younger than 8 months who are born during or entering their first season should get the antibody if the mother was not vaccinated, her status is unknown, or the baby was born within 14 days of her vaccination. Most infants born 14 or more days after maternal vaccination do not need it.
• Timing. In most of the continental United States, the antibody is given from October through the end of March. Babies born from October 1 through March 31 should ideally get it at birth or within a week.
• Second season. Nirsevimab is recommended for some children aged 8 to 19 months at increased risk, such as those with chronic lung disease of prematurity requiring medical support, severe immunocompromise, certain cystic fibrosis patients, and American Indian or Alaska Native children.

The older antibody palivizumab was scheduled to stop being available after December 31, 2025, according to the CDC. The adult vaccines are not approved for infants or young children.

The difference between the two infant strategies is worth stating plainly. A maternal vaccine is active immunization of the mother, whose antibodies cross the placenta. An infant antibody is passive immunization: finished antibodies are injected into the baby and wane over months. For why that distinction matters, see How Vaccines Train Memory B Cells. The mRNA platform behind mRESVIA is the same family used for COVID-19 vaccines, described in mRNA Vaccines: COVID-19 Breakthrough Explained.

Diagnosis and treatment

Most healthy adults with RSV are never tested. For infants and hospitalized patients, laboratory tests such as nucleic acid tests or antigen tests can identify the virus, and the result can guide isolation and care decisions.

Treatment is mostly supportive. The CDC's clinical overview says infants who need hospital care may receive oxygen, rehydration, or mechanical ventilation, and that most improve within a few days. There is no routine, widely used antiviral. The Canadian data sheet says ribavirin has been used in severe cases but that recent studies suggest it provides no significant benefit. Several drug candidates are in clinical development, and any specific product should be checked against current regulatory approvals.

What people often get wrong about RSV

"RSV is just a children's cold." For most older children and healthy adults it is a cold, but it is the most common cause of infant hospitalization in the United States and a significant cause of hospitalization in older adults.

"Two to three percent of infected infants are hospitalized." The CDC figure is about 2 to 3 percent of all infants under six months each year, which is a different measure.

"The first vaccine failed because the virus is too variable." The 1960s failure was an immune-response problem. The formalin-inactivated vaccine produced a poor-quality antibody and a harmful T-cell pattern. The virus's variability is real, but it was not the cause.

"Once you have had it, you are protected." Reinfection occurs throughout life, though later infections tend to be milder.

"The new antibody is a vaccine." Nirsevimab and clesrovimab are monoclonal antibodies. They provide protection directly for a season, without training the infant's immune system.

"RSV spreads like a measles-style airborne virus." Measles is a classic airborne virus. According to the Canadian data sheet, RSV transmission is mainly by contact and large droplets, and small-particle aerosol spread is less likely. Hand hygiene and cleaning surfaces matter. The measles article in the reading list below shows the contrast.

FAQ

Q: How is RSV different from a cold? A: In many people RSV causes cold-like symptoms: congestion, cough, sore throat, and fatigue. The difference is in who can become severely ill. In infants and older adults RSV can reach the lower airways and cause bronchiolitis or pneumonia, and it can worsen asthma, COPD, and heart failure.

Q: Can adults get RSV more than once? A: Yes. Immunity after infection is incomplete, and reinfection occurs throughout life. Later infections are usually milder. The vaccines for older adults are designed to strengthen protection in people whose risk of severe disease is higher.

Q: Is there a specific antiviral for RSV? A: Not one in routine use. Treatment is supportive, such as oxygen, fluids, and breathing support when needed. Ribavirin has been used in severe cases, but recent studies suggest no significant benefit. Candidate antivirals are in development.

Q: Who should get an RSV vaccine? A: As of CDC guidance dated August 2025, a single dose is recommended for all adults 75 and older and for adults 50 to 74 at increased risk, and a maternal vaccine is recommended at 32 to 36 weeks of pregnancy as one way to protect newborns. Guidance changes, so the decision should be made with a health care provider.

Q: If a mother got the RSV vaccine, does the baby also need nirsevimab? A: Usually not. The CDC says most infants born 14 or more days after maternal vaccination do not need the infant antibody. It is recommended if the mother was not vaccinated, her status is unknown, or the baby was born within 14 days of her vaccination.

Q: Why did the first RSV vaccine make disease worse? A: In the 1960s, children given a formalin-inactivated vaccine developed more severe illness on later infection, with 80 percent of infected vaccinees hospitalized versus 5 percent of controls. Leading explanations include non-neutralizing antibody, a Th2-skewed T-cell response, and immune complexes, though the exact mechanism has not been settled.

Q: Is the RSV mRNA vaccine the same technology as the COVID-19 mRNA vaccines? A: It uses the same family of mRNA delivery technology. The difference is the protein encoded: mRESVIA encodes the RSV prefusion F protein, while the COVID-19 vaccines encode the SARS-CoV-2 spike protein.

The takeaway

RSV shows how much a virus's danger depends on who it meets. The same virus is a cold in a healthy adult and a hospital admission in a small baby, because airway size, immune experience, and chronic disease change what a modest infection does.

It also shows how prevention can stall for the right reason and restart for another. A vaccine that increased disease in 1966 taught researchers to be careful about the kind of immune response they induced, and a structural insight in 2013, that the useful target is a spring-loaded protein held in the right shape, made a new generation of vaccines possible. The tools that arrived from 2023 onward work because someone first understood what the F protein looks like before it fires.

Sources

• CDC. RSV clinical overview, updated August 2025. Infant and young-child RSV immunization guidance. RSV surveillance and seasonality.
• Immunize.org. Ask the Experts: RSV disease issues, reviewed August 24, 2025.
• Li, Y., et al. (2022). Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019. The Lancet, 399(10340), 2047-2064.
• U.S. Food and Drug Administration. Abrysvo approval for use in pregnancy, August 21, 2023. Beyfortus approval, July 17, 2023.
• Public Health Agency of Canada. Respiratory syncytial virus: pathogen safety data sheet.
• Shang, Z., et al. (2021). The structure and pathology of RSV. International Journal of Biological Sciences, 17(14), 4073-4091. Full text.
• Casadevall, A., et al. (2025). The story behind the science: on the discovery of respiratory syncytial virus. mBio. Full text.
• Review of enhanced disease after formalin-inactivated RSV vaccine. PubMed Central.
• McLellan, J.S., et al. (2013). Structure-based design of a fusion glycoprotein vaccine for respiratory syncytial virus. Science, 342, 592-598.
• Walsh, E.E., et al. (2023). Efficacy and safety of a bivalent RSV prefusion F vaccine in older adults. New England Journal of Medicine.

---

Read next:

• HPV Explained — How the Virus Causes Cancer and How the Vaccine Works
• Influenza Virus Explained — How Seasonal Flu Actually Works
• Measles Virus Explained — Why It's Coming Back in 2026
• H5N1 Bird Flu Explained — How the Virus Works in 2026