Respiratory syncytial virus vaccines: the time has finally come (2023)


Bundle 34, number 30,

June 24, 2016

, page 3535-3541

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Respiratory syncytial viruscauses significantPublic healthstrain, particularly in very young infants and the frail elderly. Inheritance of RSV enhanced disease (ERD) from whole formalin-inactivatedRSV-vaccineand complex biologyvirusand newborns have delayed the development of effective vaccines. However, new insight into the factors associated withERDand breakthroughs in understanding the structure of the fusion antigen (F)glycoproteinhas increased optimism that vaccine development is possible. This has led to the investment of time and resources by industry, regulatory agencies, governments and non-profit organizations to develop the necessary infrastructure to make advanced clinical development of RSV vaccine candidates a reality.

Section excerpt


Respiratory syncytial virus (RSV) is the most common cause of hospitalization in children under 5 years of age [1]. In developing countries, RSV also causes significant mortality in children under 1 year of age [2]. All children are infected by the age of 3, and people are infected many times during their lifetime [3]. In otherwise healthy children over 5 years of age and adults, RSV usually causes an upper respiratory tract syndrome, sometimes complicated by sinusitis and otitis media [4], [5]. IN


RSV infects the ciliated epithelium of the upper and lower respiratory tract. The bronchiolar epithelium is particularly susceptible to infection, and type I pneumocytes in the alveoli are also frequently infected, resulting in a high incidence (~20%) of children with hypoxemia, even in those without other significant symptoms. In children with severe RSV disease, the main feature of the pathology is thought to be airway obstruction. Several autopsy studies of fatal RSV infection show that the small airways can

Purpose of vaccination

The primary clinical goal of RSV vaccine is to prevent severe lower respiratory tract disease in young infants. End points will include prevention of hospitalization or medical management of lower respiratory tract infection (MALRI) in industrialized countries, prevention of mortality and hospitalization or MALRI in developing countries and, if possible, development of a clinical severity index as continuous variable of disease severity. Secondary objectives are: (1) medical prevention;


RSV is a pneumovirus from the Paramyxoviridae family. It has a single-stranded, negative-sense RNA genome of about 15 kilobases with 10 genes separated by stop/start sequences that encode 11 known proteins. There are two main subtypes of RSV, characterized mainly by variations in the G-glycoprotein [22]. Subtypes tend to alternate in dominance from year to year, but they circulate together and are not exclusive to a single era. Although there is genetic variation between characteristic strains

Surface proteins

There are three proteins in the lipid envelope that are exposed on the surface of the virus, including SH (small hydrophobic), G and F (fusion) [24]. SH is a 64–65 amino acid pentameric ion channel analog of the M2 protein of influenza virus. G is a highly glycosylated integral membrane type II protein 298 amino acids in length with a molecular weight of ca. 90 kDa. Its main characteristics include a high serine/threonine content of close to 30%, resulting in a high level of O-glycosylation and approximately 10%

Correlations of immunity

The basis for frequent re-infections with RSV is not known. The fact that there is relatively little genetic variation suggests that it relies on other mechanisms of immune evasion. One possibility is that induction of immunity at the initial event is ineffective and permanently alters the ability to achieve sustained immunity. Initial exposure often occurs in very young children in the presence of maternal antibodies and in hosts with a tendency toward lower IFN activity. These

Disease caused by vaccines

Vaccine-induced illness syndrome has been associated with immunization of antigen-naive infants with formalin-inactivated whole RSV (FI-RSV) formulated in alum [57] , [58] , [59] , [60] . Although the exact mechanism behind RSV disease (ERD) of FI-RSV is unknown, two major immunological phenomena are associated with this syndrome based on pathological evaluation from initial cases [61], [62] and extensive mouse studies. cotton rats, non-human primates (NHP) and cattle

The vaccine is coming

Since the FI-RSV vaccine episode, approaches with intranasally administered live attenuated or chimeric live vectors have progressed to antigen-naive infants. However, in recent years there has been a large increase in the number and variety of RSV vaccine candidates (Table 1). Live attenuated and chimeric live vectors are not associated with ERD and are generally safe and well tolerated [73]. Some of the more recent designs have shown higher levels of immunogenicity

F structure and implications for vaccine development

Solving the crystal structure of the trimeric F-glycoprotein in its prefusion conformation is a recent discovery that led to RSV vaccine development [29], [86], [87]. Prefusion F (pre-F) surfaces target antibodies from several different competitive binding moieties, five of which are currently published [27], [28]. Only two of these sites exist on the common surface that remains in the F (post-F) trimer after fusion, which is the end product of the bulk


RSV is a major cause of morbidity and mortality and is a high priority for vaccine development. Despite the fact that humans are frequently reinfected with RSV despite the lack of significant genetic variation and the heritability of FI-RSV ERD, there is optimism that a vaccine solution to prevent severe disease is possible. This is based on new insights into virus morphology, the atomic-level structure of F-glycoprotein in pre- and post-F conformational states, virus mechanisms


This project was funded by intramural fundingCenter for Vaccine Research, National Institute of Allergy and Infectious Diseases, NIH. The author is the named inventor of patents for RSV vaccines involving F subunit proteins and vector gene delivery of F. I thank Jason Gallo and Kaitlyn Morabito for thoughtful editorial comments on the manuscript.


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      Antiviral drugs against RSV may not be able to improve the clinical course when RSV infection of the lower respiratory tract is established. Future studies of RSV antivirals should focus on early intervention and more accurate measurement of objective outcomes before significant lower respiratory tract inflammation occurs.

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    Has there ever been a vaccine for RSV? ›

    Today, the U.S. Food and Drug Administration approved Arexvy, the first respiratory syncytial virus (RSV) vaccine approved for use in the United States. Arexvy is approved for the prevention of lower respiratory tract disease caused by RSV in individuals 60 years of age and older.

    How long has the RSV vaccine been around? ›

    RSV vaccines

    RSV vaccine development began in the 1960s with an unsuccessful formalin-inactivated RSV (FI-RSV) vaccine that induced a severe – and in two cases lethal – lung inflammatory response during the first natural RSV infection after vaccination of RSV-naive infants.

    How long does the RSV vaccine last? ›

    So far, GSK found that protection from a single vaccination protects older people through an entire respiratory disease season, and potentially up to a year.

    What is the progress of the RSV vaccine? ›

    In March 2022 AstraZeneca and Sanofi announced that their long-acting antibody, nirsevimab, is 75 percent effective against cases of RSV that require medical care in infants younger than one year old with no history of RSV—and the protection lasts five months.

    Why hasn t there been a vaccine for RSV? ›

    Instead of protecting against RSV, the experimental vaccine made the children more likely to develop more severe illnesses if they got infected. Many children in the trial were hospitalized, and two young children died. “That was a disaster,” Levy said, “and it set the field back by 20 to 30 years.”

    Why did the RSV vaccine fail? ›

    Most notably, the adjuvants strongly activated type 1 T-helper (Th1) responses, which are essential in defending against viruses. These responses have been hard to stimulate in newborns. In fact, a major reason the earlier RSV vaccine failed was that it did not produce a Th1 response.

    Has the RSV vaccine trial stopped? ›

    GlaxoSmithKline (GSK) last year stopped a late-stage clinical trial of its RSV vaccine in pregnant people over an elevated risk of premature birth and associated neonatal deaths in the babies born prematurely. In the GSK trial, premature birth was 38% more likely in the vaccinated pregnancies than in the placebo group.

    Is Pfizer making a vaccine for RSV? ›

    In February 2023, it was announced that the European Medicines Agency (EMA) accepted for review Pfizer's Marketing Authorization Application (MAA) under accelerated assessmentfor RSVpreF, as submitted for both older adults and maternal immunization to help protect infants against RSV.

    Is RSV vaccine a live vaccine? ›

    Live-attenuated respiratory syncytial virus (RSV) vaccines offer several advantages for immunization of infants and young children: (1) they do not cause vaccine-associated enhanced RSV disease; (2) they broadly stimulate innate, humoral, and cellular immunity, both systemically and locally in the respiratory tract; (3 ...

    Do adults need RSV vaccine? ›

    FDA approves world's first RSV vaccine, a shot for adults ages 60 and up. GSK's single-dose shot lowered the risk of severe illness by 94% in older adults. The Food and Drug Administration on Wednesday approved the world's first RSV vaccine: a shot for adults ages 60 and up, made by pharmaceutical giant GSK.

    Should seniors get RSV vaccine? ›

    The panel recommended that the agency approve both. The GSK vaccine was nearly 83 percent effective in preventing lower respiratory tract illness in adults 60 and older in a study of about 25,000 patients, according to data published in The New England Journal of Medicine.

    Is RSV vaccine safe? ›

    A vaccine against respiratory syncytial virus (RSV) was effective at preventing RSV-associated illness among older adults and the children of vaccinated mothers, based on interim results from 2 phase 3 trials.

    Is RSV vaccine FDA approved? ›

    The US Food and Drug Administration on Wednesday approved Pfizer's RSV vaccine for older adults, the second such shot approved for the common virus. Earlier in May, the agency approved the world's first RSV vaccine for older adults, made by GSK.

    What are the challenges with RSV vaccine? ›

    However, vaccine development for RSV faces several challenges unique to RSV: first is the young age of infection; second is the multiple mechanisms RSV uses to evade innate immunity; third is the lack of durable protective immunity induced by natural infection; fourth, a legacy of vaccine-enhanced disease dating back ...

    Do babies get shots to prevent RSV? ›

    There is no vaccine yet to prevent RSV infection, but scientists are working hard to develop one. And there is a medicine that can help protect some babies at high risk for severe RSV disease.

    When is RSV season over 2023? ›

    On March 1, 2023, the Health and Human Services Commission (HHSC) will end Synagis prophylaxis therapy for the season's respiratory syncytial virus (RSV) in all regions.

    Is RSV a Covid? ›

    What is the difference between the flu, COVID-19, and RSV? The flu, COVID-19, and respiratory syncytial virus (RSV) are all highly contagious respiratory infections caused by viruses: The flu by influenza virus, COVID-19 by SARS-CoV-2 virus, and RSV by respiratory syncytial virus.

    Can you get RSV twice? ›

    Infants and older adults may develop severe infections from RSV, such as pneumonia or bronchiolitis. Most kids get an RSV infection by age 2. However, you can get an RSV infection at any age and more than once in your lifetime.

    Why is RSV called syncytial? ›

    Its name is derived from the large cells known as syncytia that form when infected cells fuse. RSV is the single most common cause of respiratory hospitalization in infants, and reinfection remains common in later life: it is a notable pathogen in all age groups.

    How effective is the RSV vaccine? ›

    In an RSV challenge study involving healthy persons who were 18 to 50 years of age, the vaccine efficacy was 87% (95% confidence interval [CI], 54 to 96) against symptomatic RSV infection confirmed by any detectable viral RNA on at least 2 consecutive days.

    How long has SYNAGIS been out? ›

    For nearly 20 years SYNAGIS has been prescribed to high-risk infants and children to help reduce the risk of RSV-related hospitalizations.

    Why are more adults getting RSV? ›

    Older adults are at greater risk than young adults for serious complications from RSV because our immune systems weaken when we are older. Wash your hands often with soap and water for at least 20 seconds.

    Is RSV and whooping cough the same? ›

    Respiratory syncytial virus, or RSV, and pertussis, commonly called whooping cough, are not likely to cause serious health issues for otherwise healthy adults, but it's still very important for everyone to take precautions against both.

    Who is most at risk for RSV? ›

    Risk factors

    People at increased risk of severe or sometimes life-threatening RSV infections include: Infants, especially premature infants or babies who are 6 months or younger. Children who have heart disease that's present from birth (congenital heart disease) or chronic lung disease.

    Who should get RSV vaccine? ›

    Q: Who should get the RSV vaccine? A: Anyone 65 and older with any kind of lung disease, heart disease or other underlying conditions that may cause them to have problems when they get an infection should consider getting the RSV vaccine.

    How much does RSV vaccine cost? ›

    Outcomes Measure Incremental cost (2010 US dollars) per hospitalization for RSV infection avoided. Results The mean cost of palivizumab per dose ranged from $1661 for infants younger than 6 months of age to $2584 for children in their second year of life.

    How much is the SYNAGIS shot? ›

    The cost for Synagis intramuscular solution (100 mg/mL) is around $1,844 for a supply of 0.5 milliliters, depending on the pharmacy you visit. Quoted prices are for cash-paying customers and are not valid with insurance plans.
    Intramuscular Solution.
    QuantityPer unitPrice
    1 milliliter$3,473.75$3,473.75
    1 more row

    What does RSV look like in adults? ›

    Usually, as an adult, when you become ill with RSV you have mild cold-like symptoms such as a runny nose, sore throat, cough and a headache. But sometimes, and for some people, you can become so ill you need to be hospitalized. And each year in the United States thousands of older adults die of complications from RSV.

    Is there a shot to protect babies from RSV? ›

    In Pfizer's international study of nearly 7,400 pregnant women, maternal vaccination proved 82 percent effective at preventing severe RSV during babies' most vulnerable first three months of life. At age 6 months, it still was proving 69 percent protective against severe illness.

    Is there a vaccine to prevent RSV in babies? ›

    A drug called palivizumab (pah-lih-VIH-zu-mahb) is available to prevent severe RSV illness in certain infants and children who are at high risk for severe disease. This could include, for example, infants born prematurely or with congenital (present from birth) heart disease or chronic lung disease.

    What did RSV used to be called? ›

    RSV was first discovered in 1956 when researchers isolated a virus from a population of chimpanzees with respiratory illness. They named the virus CCA (Chimpanzee Coryza Agent).

    Who qualifies for RSV vaccine? ›

    Infants, especially those 6 months and younger. Children younger than 2 years old with chronic lung disease or congenital heart disease. Children with suppressed immune systems. Children who have neuromuscular disorders, including those who have difficulty swallowing or clearing mucus secretions.

    How much do SYNAGIS shots cost? ›

    The cost for Synagis intramuscular solution (100 mg/mL) is around $1,844 for a supply of 0.5 milliliters, depending on the pharmacy you visit. Quoted prices are for cash-paying customers and are not valid with insurance plans.
    Intramuscular Solution.
    QuantityPer unitPrice
    1 milliliter$3,473.75$3,473.75
    1 more row

    Is the RSV vaccine safe? ›

    A committee of advisers to the U.S. Food and Drug Administration (FDA) yesterday voted unanimously that a vaccine from Pfizer, given as an injection during pregnancy, is efficacious at protecting infants from severe respiratory syncytial virus (RSV) disease during the first 6 months of life.

    Is RSV caused by Covid? ›

    The flu, COVID-19, and respiratory syncytial virus (RSV) are all highly contagious respiratory infections caused by viruses: The flu by influenza virus, COVID-19 by SARS-CoV-2 virus, and RSV by respiratory syncytial virus. It is possible for a person to be infected with multiple viruses at the same time.

    How contagious is RSV? ›

    RSV is very contagious. It can spread through the droplets released into the air when an infected person coughs or sneezes, or if you touch a contaminated surface, such as counters or doorknobs (where it can live for hours). It can also spread through direct contact (kissing the face of a child with RSV, for example).

    Why are so many kids getting RSV? ›

    Many say the uptick in cases is likely because people weren't exposed much in the past two years with masking and social distancing during the COVID-19 pandemic. Here's some information for parents to help protect children from RSV and to know the first signs of severe infection.

    Why do adults not get RSV? ›

    Yes, adults can get RSV. In fact, you've probably had RSV several times in your life. As you get older and your immune system develops more antibodies, you're able to fight off RSV more efficiently. So you may have only developed a mild cold with your RSV infection.

    Why is there so much RSV right now? ›

    If you are suddenly hearing a lot about respiratory syncytial virus (RSV), it is because the virus has come earlier and hit harder than in most years, and is currently surging and straining children's hospitals across the US


    1. Jan 12, 2022 ACIP Meeting - Respiratory Syncytial Virus Vaccines & Pneumococcal vaccines
    (Centers for Disease Control and Prevention (CDC))
    2. Respiratory Syncytial Virus (RSV)
    (Cleveland Clinic)
    3. Development of Respiratory Syncytial Virus and Universal Influenza Virus Vaccines
    4. WVU Medicine Tuesday Talks: Respiratory Syncytial Virus - RSV
    (WVU Medicine)
    5. Respiratory Syncytial Virus (RSV): Not Just a Little Kids’ Virus
    (Alliance for Aging Research)
    6. Oct 20, 2022 ACIP Meeting - Respiratory Syncytial Virus Vaccines
    (Centers for Disease Control and Prevention (CDC))


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