Monoclonal antibody | |
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Type | Whole antibody |
Source | Humanized (from mouse) |
Target | RSV protein F |
Clinical data | |
Trade names | Synagis |
AHFS/Drugs.com | Monograph |
MedlinePlus | a698034 |
License data |
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Routes of administration | Intramuscular |
ATC code | |
Legal status | |
Legal status | |
Pharmacokinetic data | |
Elimination half-life | 18-20 days |
Identifiers | |
CAS Number | |
DrugBank | |
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UNII | |
KEGG | |
ChEMBL | |
Chemical and physical data | |
Formula | C6470H10056N1700O2008S50 |
Molar mass | 145388.51 g·mol−1 |
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Palivizumab, sold under the brand name Synagis, is a monoclonal antibody produced by recombinant DNA technology used to prevent severe disease caused by respiratory syncytial virus (RSV) infections. [2] [4] It is recommended for infants at high-risk for RSV due to conditions such as prematurity or other medical problems including heart or lung diseases. [2] [4]
The most common side effects include fever and rash. [2] [4]
Palivizumab is a humanized monoclonal antibody (IgG) directed against an epitope in the A antigenic site of the F protein of RSV. In two phase III clinical trials in the pediatric population, palivizumab reduced the risk of hospitalization due to RSV infection by 55% and 45%. [5] Palivizumab is dosed once a month via intramuscular (IM) injection, to be administered throughout the duration of the RSV season, which in based on past trends has started in Mid-September to Mid-November. [2] [6] [7]
Palivizumab targets the fusion protein of RSV, [8] inhibiting its entry into the cell and thereby preventing infection. Palivizumab was approved for medical use in 1998. [9]
Palivizumab is indicated for the prevention of serious lower respiratory tract disease requiring hospitalization caused by the respiratory syncytial virus (RSV) in children at high risk for RSV disease: [2] [4] [10]
The American Academy of Pediatrics has published guidelines for the use of palivizumab. The most recent updates to these recommendations are based on new information regarding RSV seasonality, palivizumab pharmacokinetics, the incidence of bronchiolitis hospitalizations, the effect of gestational age and other risk factors on RSV hospitalization rates, the mortality of children hospitalized with RSV infection, the effect of prophylaxis on wheezing, and palivizumab-resistant RSV isolates. [11]
All infants younger than one year who were born at <29 weeks (i.e. ≤28 weeks, 6 days) of gestation are recommended to use palivizumab. Infants younger than one year with bronchopulmonary dysplasia (i.e. who were born at <32 weeks gestation and required supplemental oxygen for the first 28 days after birth) and infants younger than two years with bronchopulmonary dysplasia who require medical therapy (e.g. supplemental oxygen, glucocorticoids, diuretics) within six months of the anticipated RSV season are recommended to use palivizumab as prophylaxis. [11] Taking palivizumab prophylactically decreases the number of RSV infections, decreases wheezing, and may decrease the rate of hospitalization attributed to RSV. [12] [13] There are few negative side effects reported. [13] It is not clear if palivizumab is effective and safe for the other medical conditions that put them at a higher risk for serious cases of RSV such as deficiencies in their immune system. [13]
Since the risk of RSV decreases after the first year following birth, the use of palivizumab for children more than 12 months of age is generally not recommended with the exception of premature infants who need supplemental oxygen, bronchodilator therapy, or steroid therapy at the time of their second RSV season. [11]
Decisions regarding palivizumab prophylaxis for children in these groups should be made on a case-by-case basis. [11]
Because palivizumab is a passive antibody, it is ineffective in the treatment of RSV infection, and its administration is not recommended for this indication. [11] A 2019 (updated in 2023) Cochrane review found no differences in palivizumab and placebo on outcomes of mortality, length of hospital stay, and adverse events in infants and children aged up to 3 years old with RSV. [14] Larger RCTs will be required before palivizumab can be recommended as a treatment option. [15] If an infant has an RSV infection despite the use of palivizumab during the RSV season, monthly doses of palivizumab may be discontinued for the rest of the RSV season due to the low risk of re-hospitalization. [11] Current studies are in progress to determine new treatments for RSV rather than solely prophylaxis. [16]
Contraindications for the use of palivizumab include hypersensitivity reactions upon exposure to palivizumab. Serious cases of anaphylaxis have been reported after exposure to palivizumab. Signs of hypersensitivity include hives, shortness of breath, hypotension, and unresponsiveness. No other contraindications for palivizumab have been reported. [17] Further studies are needed to determine if any drug-drug interactions exist as none have been conducted as of yet.
Palivizumab use may cause side effects, which include, but are not limited to: [18]
Some more serious side effects include:
Palivizumab has demonstrated a significantly higher affinity and potency in neutralizing both A and B subtypes of RSV when compared with RSV-IGIV. [19] Treatment with 2.5 mg/kg of palivizumab led to a serum concentration of 25-30 μg/mL in cotton rats and reduced RSV titers by 99% in their lungs. [20]
Palivizumab is a monoclonal antibody that targets the fusion (F) glycoprotein on the surface of RSV, and deactivates it. [21] The F protein is a membrane protein responsible for fusing the virus with its target cell and is highly conserved among subgroups of RSV. Deactivating the F protein prevents the virus from fusing with its target's cell membrane and prevents the virus from entering the host cell. [21] [22]
A 2008 meta-analysis found that palivizumab absorption was quicker in the pediatric population compared to adults (ka = 1.01/day vs. ka = 0.373/day). The intramuscular bioavailability of this drug is approximately 70% in healthy young adults. [23] Current recommendation for RSV immunoprophylaxis is administration of 5 x 15 mg/kg doses of palivizumab to maintain body concentrations above 40 μg/mL. [24]
The volume of distribution is approximately 4.1 liters. [23]
Palivizumab has a drug clearance (CL) of approximately 198 ml/day. The half-life of this drug is approximately 20 days with three doses sustaining body concentrations that will last the entire RSV season (5 to 6 months). A 2008 meta-analysis estimated clearance in the pediatric population by considering maturation of CL and body weight which showed a significant reduction compared to adults. [23]
Palivizumab is a relatively expensive medication, with a 100-mg vial ranging from $904 to $1866. [25] Multiple studies done by both the manufacturer and independent researchers to determine the cost-effectiveness of palivizumab have found conflicting results. The heterogeneity between these studies makes them difficult to compare. Given that there is no consensus about the cost-effectiveness of palivizumab, usage largely depends on the location of care and individual risk factors. [26] [21] [27]
A 2013 meta-analysis reported that palivizumab prophylaxis was a dominant strategy with an incremental cost-effectiveness ratio of $2,526,203 per quality-adjusted life-year (QALY). It also showed an incremental cost-effectiveness ratio for preterm infants between $5188 and $791,265 per QALY, from the payer perspective. [28] However, as previously stated, the cost-effectiveness of palivizumab is undecided, and this meta-analysis is only one example of society can benefit from palivizumab prophylaxis.
The disease burden of RSV in young infants and its global prevalence have prompted attempts for vaccine development. As of 2019, there was no approved vaccine for RSV prevention. [29] A formalin-inactivated RSV vaccine (FIRSV) was studied in the 1960s. The immunized children who were exposed to the virus in the community developed an enhanced form of RSV disease presented by wheezing, fever, and bronchopneumonia. This enhanced form of the disease led to 80% hospitalization in the recipients of FIRSV compared to 5% in the control group. Additionally, 2 fatalities occurred among the vaccine recipients upon reinfection in subsequent years. [30] Subsequent attempts to develop an attenuated live virus vaccine with optimal immune response and minimal reactogenicity have been unsuccessful. [31] Further research on animal subjects suggested that intravenously administered immunoglobulin with high RSV neutralizing activity can protect against RSV infection. [32] In 1995, the U.S. Food and Drug Administration (FDA) approved the use of RespiGam (RSV-IGIV) for the prevention of serious lower respiratory tract infection caused by RSV in children younger than 24 months of age with bronchopulmonary dysplasia or a history of premature birth. [33] The success of the RSV-IGIV demonstrated efficacy in immunoprophylaxis and prompted research into further technologies. Thus, Palivizumab was developed as an antibody that was found to be fifty times more potent than its predecessor. This antibody has been widely used for RSV since 1998 when it was approved. [34]
Palivizumab, originally known as MEDI-493, was developed as an RSV immune prophylaxis tool that was easier to administer and more effective than the current tools of that time (the 1990s). [34] It was developed over a 10-year period by MedImmune Inc. by combining human and mouse DNA. [35] Specifically, antibody production was stimulated in a mouse model following immunization with RSV. The antibody-producing B cells were isolated from the mouse's spleen and fused with mouse myeloma cell lines. The antibodies were then humanized by cloning and sequencing the DNA from both the heavy and light chains of the monoclonal antibody. Overall, the monoclonal antibody is 95% similar to other human antibodies with the other 5% having DNA origins from the original mouse. [20]
The common cold or the cold is a viral infectious disease of the upper respiratory tract that primarily affects the respiratory mucosa of the nose, throat, sinuses, and larynx. Signs and symptoms may appear in as little as two days after exposure to the virus. These may include coughing, sore throat, runny nose, sneezing, headache, and fever. People usually recover in seven to ten days, but some symptoms may last up to three weeks. Occasionally, those with other health problems may develop pneumonia.
Bronchiolitis is inflammation of the small airways in the lungs. Acute bronchiolitis is due to a viral infection usually affecting children younger than two years of age. Symptoms may include fever, cough, runny nose, wheezing, and breathing problems. More severe cases may be associated with nasal flaring, grunting, or the skin between the ribs pulling in with breathing. If the child has not been able to feed properly, signs of dehydration may be present.
Respiratory syncytial virus (RSV), also called human respiratory syncytial virus (hRSV) and human orthopneumovirus, is a contagious virus that causes infections of the respiratory tract. It is a negative-sense, single-stranded RNA virus. Its name is derived from the large cells known as syncytia that form when infected cells fuse.
Human metapneumovirus is a negative-sense single-stranded RNA virus of the family Pneumoviridae and is closely related to the Avian metapneumovirus (AMPV) subgroup C. It was isolated for the first time in 2001 in the Netherlands by using the RAP-PCR technique for identification of unknown viruses growing in cultured cells. As of 2016, it was the second most common cause of acute respiratory tract illness in otherwise-healthy children under the age of 5 in a large US outpatient clinic.
In immunology, antiserum is a blood serum containing antibodies that is used to spread passive immunity to many diseases via blood donation (plasmapheresis). For example, convalescent serum, passive antibody transfusion from a previous human survivor, used to be the only known effective treatment for ebola infection with a high success rate of 7 out of 8 patients surviving.
Oseltamivir, sold under the brand name Tamiflu, is an antiviral medication used to treat and prevent influenza A and influenza B, viruses that cause the flu. Many medical organizations recommend it in people who have complications or are at high risk of complications within 48 hours of first symptoms of infection. They recommend it to prevent infection in those at high risk, but not the general population. The Centers for Disease Control and Prevention (CDC) recommends that clinicians use their discretion to treat those at lower risk who present within 48 hours of first symptoms of infection. It is taken by mouth, either as a pill or liquid.
Human parainfluenza viruses (HPIVs) are the viruses that cause human parainfluenza. HPIVs are a paraphyletic group of four distinct single-stranded RNA viruses belonging to the Paramyxoviridae family. These viruses are closely associated with both human and veterinary disease. Virions are approximately 150–250 nm in size and contain negative sense RNA with a genome encompassing about 15,000 nucleotides.
Community-acquired pneumonia (CAP) refers to pneumonia contracted by a person outside of the healthcare system. In contrast, hospital-acquired pneumonia (HAP) is seen in patients who have recently visited a hospital or who live in long-term care facilities. CAP is common, affecting people of all ages, and its symptoms occur as a result of oxygen-absorbing areas of the lung (alveoli) filling with fluid. This inhibits lung function, causing dyspnea, fever, chest pains and cough.
Gregory Antone Prince is an American pathology researcher, businessman, author, social critic, and historian of the Latter Day Saint movement.
Motavizumab is a humanized monoclonal antibody. It is being investigated by MedImmune for the prevention of respiratory syncytial virus infection in high-risk infants. As of September 2009, it was undergoing Phase II and III clinical trials.
Influenza-like illness (ILI), also known as flu-like syndrome or flu-like symptoms, is a medical diagnosis of possible influenza or other illness causing a set of common symptoms. These include fever, shivering, chills, malaise, dry cough, loss of appetite, body aches, nausea, and sneezing typically in connection with a sudden onset of illness. In most cases, the symptoms are caused by cytokines released by immune system activation, and are thus relatively non-specific.
Neonatal infections are infections of the neonate (newborn) acquired during prenatal development or within the first four weeks of life. Neonatal infections may be contracted by mother to child transmission, in the birth canal during childbirth, or after birth. Neonatal infections may present soon after delivery, or take several weeks to show symptoms. Some neonatal infections such as HIV, hepatitis B, and malaria do not become apparent until much later. Signs and symptoms of infection may include respiratory distress, temperature instability, irritability, poor feeding, failure to thrive, persistent crying and skin rashes.
The genus Orthopneumovirus consists of pathogens that target the upper respiratory tract within their specific hosts. Every orthopneumovirus is characterized as host-specific, and has a range of diseases involved with respiratory illness. Orthopneumoviruses can cause diseases that range from a less-severe upper-respiratory illness to severe bronchiolitis or pneumonia. Orthopneumoviruses are found among sheep, cows, and most importantly humans. In humans, the orthopneumovirus that specifically impacts infants and small children is known as human respiratory syncytial virus.
A respiratory syncytial virus vaccine, or RSV vaccine, is a vaccine that protects against respiratory syncytial virus. RSV affects an estimated 64 million people and causes 160,000 deaths worldwide each year.
Jason S. McLellan is a structural biologist, professor in the Department of Molecular Biosciences and Robert A. Welch Chair in Chemistry at The University of Texas at Austin who specializes in understanding the structure and function of viral proteins, including those of coronaviruses. His research focuses on applying structural information to the rational design of vaccines and other therapies for viruses, including SARS-CoV-2, the novel coronavirus that causes COVID-19, and respiratory syncytial virus (RSV). McLellan and his team collaborated with researchers at the National Institute of Allergy and Infectious Diseases’ Vaccine Research Center to design a stabilized version of the SARS-CoV-2 spike protein, which biotechnology company Moderna used as the basis for the vaccine mRNA-1273, the first COVID-19 vaccine candidate to enter phase I clinical trials in the U.S. At least three other vaccines use this modified spike protein: those from Pfizer and BioNTech; Johnson & Johnson and Janssen Pharmaceuticals; and Novavax.
Anna Banerji M.D., O. Ont. is a Toronto infectious disease doctor, tropical disease specialist, pediatrician, public health specialist, academic, and activist. She is the founder and chair of both the North American Refugee Health Conference in Canada and the Indigenous Health Conference, and the co-founder of the Society of Refugee Healthcare Providers. She was awarded the Dr Peter Bryce Henderson for her advocacy for Indigenous children.
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Passive antibody therapy, also called serum therapy, is a subtype of passive immunotherapy that administers antibodies to target and kill pathogens or cancer cells. It is designed to draw support from foreign antibodies that are donated from a person, extracted from animals, or made in the laboratory to elicit an immune response instead of relying on the innate immune system to fight disease. It has a long history from the 18th century for treating infectious diseases and is now a common cancer treatment. The mechanism of actions include: antagonistic and agonistic reaction, complement-dependent cytotoxicity (CDC), and antibody-dependent cellular cytotoxicity (ADCC).
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