Table of Contents
Introduction
Respiratory syncytial virus (RSV) is a common and contagious virus that causes respiratory infections in people of all ages. However, for some groups, such as infants, older adults, and people with weakened immune systems, RSV can lead to serious and life-threatening complications, such as pneumonia, bronchiolitis, and respiratory failure. According to the Centers for Disease Control and Prevention (CDC), RSV kills more than a hundred babies and 10,000 adults over the age of 65 in the US every year. Despite its high morbidity and mortality, there is no approved vaccine or antiviral medication for RSV prevention or treatment. The only available option is a monoclonal antibody therapy that is expensive and has limited availability. However, this situation may change soon with the recent approval of Arexvy, the first RSV vaccine in the US. In this article, we will explore how Arexvy works, what are its benefits and challenges, and what are the future directions for RSV vaccine development.
FDA Approves RSV Vaccine
The FDA has approved Arexvy, a new vaccine that can protect older adults from respiratory syncytial virus (RSV), a common and potentially deadly infection of the lungs and airways. Arexvy is the first RSV vaccine to be approved by the FDA and the European Medicines Agency. It is given as a single dose by injection into the upper arm. Arexvy is a breakthrough in preventing a major cause of respiratory illness and death in older adults. It works by stimulating the immune system to produce antibodies against a protein on the surface of the virus called RSVPreF3. Arexvy has been shown to reduce the risk of developing RSV-associated lower respiratory tract disease by more than 80% and severe disease by more than 90% in adults aged 60 years and older. Arexvy is expected to be available in the US market by early 2024.
Arexvy: RSV Vaccine for adults
Arexvy by GlaxoSmithKline is the first respiratory syncytial virus (RSV) vaccine for older adult. Arexvy is a product of GlaxoSmithKline Biologicals SA, a global pharmaceutical company that specializes in vaccines and biologics. Arexvy is an adjuvanted vaccine that contains a recombinant protein derived from the RSV fusion (F) glycoprotein, called RSVPreF3. The adjuvant is a substance that enhances the immune response to the vaccine antigen1.
The journey of Arexvy development started in 2011. Arexvy, also called AReSVi-006, is backed with highly significant statistical data from phase IIII clinical trials. The pivotal phase III trial initiated in 2019 and enrolled more than 25,000 adults aged 60 years and older from 14 countries. Trial assessed the efficiency of single dose RSV vaccine in preventing lower respiratory tract disease (LRTD) caused by RSV. LRTD is characterized with conditions that affect the lungs and airways such as pneumonia and bronchiolitis. The trial also measured the efficacy of Arexvy in preventing severe LRTD, hospitalization due to RSV-LRTD, and death due to any cause. The trial ended in results with with high statistical significance and clinical relevance. The vaccine reduced the risk of RSV-LRTD by 82.6% and the risk of severe RSV-LRTD by 94.6% in adults aged 60 years and older. The vaccine also reduced the risk of hospitalization due to RSV-LRTD by 87.5% and the risk of death due to any cause by 46.4% in the same population. The vaccine was generally well tolerated and had a similar safety profile to placebo.
Based on promising phase-4 clinical trials, GSK Arexvy got approval from FDA in April, 2023 followed by approval from European Medicine Agency in June, 2023 for individuals 60 years of age or older. Arexvy is the first vaccine ever approved for RSV infection. GSK expects to launch Arexvy in the US market by early 2024 and in other markets as soon as possible after approval.
How RSV Vaccine works
Arexvy contains a version of a protein found on the surface of the virus called RSVPreF3. Arexvy works by ‘teaching’ the immune system (the body’s natural defenses) how to defend itself against a disease. Arexvy contains a protein from the surface of the RSV virus. When a person is given the vaccine, the immune system treats the virus proteins as ‘foreign’ and makes defenses against them. If, later on, the vaccinated person comes into contact with the virus, the immune system will recognize the virus proteins and be prepared to attack it. This will help to protect against LRTD caused by the virus.
Advantages of RSV Vaccine
Arexvy is a subunit vaccine that contains a recombinant protein derived from the surface of RSV. It stimulates the immune system to produce antibodies that can neutralize RSV and prevent it from infecting the cells of the lower respiratory tract. Arexvy has several advantages over other preventive measures, such as:
- Arexvy is administered as a single dose, which is convenient and cost-effective compared to other preventive measures that require multiple doses or monthly injections. For example, palivizumab, a monoclonal antibody therapy that is given to high-risk infants and children to prevent severe RSV disease, requires five injections during the RSV season and costs about $5,000 per course.
- Arexvy is expected to have a long-lasting effect, as participants will remain in the study through three RSV seasons to assess the duration of effectiveness and the safety and effectiveness of repeat vaccination. This means that Arexvy could provide protection for several years after a single dose, unlike other preventive measures that need to be repeated every season.
- It is expected to have a herd immunity effect, as it could reduce the transmission of RSV from older adults to younger children or other vulnerable groups. This means that Arexvy could indirectly protect those who are not vaccinated or eligible for vaccination, such as infants, pregnant women, and people with weak immune systems. This could also reduce the overall incidence and severity of RSV disease in the population.
Side Effects of RSV Vaccine
Every vaccine or drug comes with some undesired side effects that sometimes, may outweigh the benefit. Here is a brief overview of the side effects of Arexvy.
Common Side Effects of Arexvy RSV Vaccine
These are related to the injection site and the general body reactions. They include injection site pain, fatigue, muscle pain, headache and joint pain. They are usually mild and last for a few days after vaccination. They can be relieved by applying a cold compress, taking pain relievers, drinking fluids, and resting.
Severe Side Effects of Arexvy RSV Vaccine
These are rare but serious. They include atrial fibrillation (irregular heart rhythm), Guillain-Barré syndrome (GBS) (a neurological disorder that causes weakness, numbness, tingling, or paralysis), and acute disseminated encephalomyelitis (ADEM) (another neurological disorder that causes inflammation and damage to the brain and spinal cord). They can cause chest pain, shortness of breath, dizziness, fainting, difficulty walking, speaking, swallowing, or breathing, headache, fever, confusion, seizures, vision loss, or coma. They require immediate medical attention and treatment. They may be caused by the vaccine or other factors. These severe side effects are very rare and have also been reported with other vaccines and infections, including RSV infection itself.
Challenges and Limitations of RSV Vaccine
Although the recent approval of Arexvy, the first RSV vaccine in the US, is a major breakthrough that could save thousands of lives and reduce the burden of RSV on the healthcare system, it is not a perfect solution and has some challenges and limitations that need to be addressed. Some of these are:
- Arexvy is not approved for use in children or pregnant women, who are also at high risk of severe RSV disease. Children under 5 years of age account for about 90% of hospitalizations due to RSV, and pregnant women can pass the infection to their unborn babies or newborns. More studies are needed to evaluate the safety and effectiveness of Arexvy in these populations. The FDA has recently approved another vaccine called Abrysvo, which is given to older adults of 60 years or more and pregnant women at 32 through 36 weeks gestational age of pregnancy to prevent lower respiratory tract disease and severe lower respiratory tract disease caused by RSV in infants from birth through 6 months of age. However, this vaccine does not protect the mothers themselves or the infants after 6 months of age.
- First RSV vaccine is not effective against all strains of RSV, as there are two major types (A and B) and many subtypes that circulate each season. The vaccine is based on a recombinant protein derived from the surface of RSV type A, which is more prevalent and virulent than type B. However, type B can also cause severe disease and may become more dominant in some seasons. More studies are needed to evaluate the cross-protection of Arexvy against different strains of RSV and whether it needs to be updated or combined with other vaccines to cover the diversity of RSV.
- Arexvy is not a cure for RSV infection, as it only prevents lower respiratory tract disease but not upper respiratory tract infection or cold-like symptoms. This means that people who are vaccinated with Arexvy can still get infected with RSV and spread it to others, especially if they have mild or asymptomatic infections. More research is needed to develop antiviral medications that can treat RSV infection once it occurs and reduce the viral load and transmission. Currently, there is no approved antiviral medication for RSV, but some candidates are under clinical trials.
The future directions for RSV vaccine development include expanding the target populations, improving the efficacy and safety, and addressing the diversity and variability of RSV. Some of the strategies that are being explored are:
- Developing live attenuated vaccines that can mimic natural infection and induce both humoral and cellular immunity. These vaccines can be administered intranasally or orally, which may be more convenient and acceptable than injections.
- Developing vectored vaccines that use harmless viruses or bacteria to deliver RSV antigens into the cells. These vaccines can elicit strong immune responses and may be able to protect against multiple strains of RSV.
- Developing universal vaccines that target conserved regions or epitopes of RSV that are shared by all types and subtypes. These vaccines can overcome the antigenic variation and escape of RSV and provide broad and durable protection.
RSV vaccine development is a challenging but promising field that has made significant progress in recent years. The approval of Arexvy is a major milestone that could save thousands of lives and reduce the burden of RSV on the healthcare system. However, more work is needed to improve the existing vaccines and develop new ones that can protect all people from this deadly virus.
Other RSV Vaccines in Development
The journey of the RSV vaccine doesn’t stop at Arexvy. Many other major pharmaceuticals are in the process of developing RSV vaccines. Below is a brief overview of other candidate vaccines in development.
- FDA approved another RSV vaccine in June, 2023 that is from Pfizer. Abrysvo is a new vaccine that prevents lower respiratory tract disease and severe lower respiratory tract disease caused by respiratory syncytial virus (RSV) in infants from birth through 6 months of age. It is given older adults and pregnant women at 32 through 36 weeks gestational age of pregnancy to protect their unborn babies or newborns from RSV infection. Pfizer RSV vaccine is also a subunit vaccine that contains a recombinant protein derived from the surface of RSV. Abrysvo is expected to reduce the risk of severe lower respiratory tract disease by 81.8% within 90 days after birth, and 69.4% within 180 days after birth. Abrysvo also reduces the risk of lower respiratory tract disease by 34.7%, and reduces the risk of severe lower respiratory tract disease by 91.1% within 90 days after birth when compared to placebo. The most common side effects reported by pregnant women who received Abrysvo were injection site pain, fatigue, muscle pain, headache and joint stiffness/pain.
- mRNA-1345 from moderna contains a single strand of messenger RNA (mRNA) that codes for a protein called prefusion F. This protein is found on the surface of the RSV virus and helps it to infect human cells. The vaccine delivers the mRNA to the cells using lipid nanoparticles (LNPs), which are the same as those used in the Moderna COVID-19 vaccines. The cells then produce the prefusion F protein, which stimulates the immune system to make antibodies against it. These antibodies can block the virus from entering the cells and prevent or reduce the severity of RSV infection. The prefusion F protein is more effective at inducing neutralizing antibodies than the postfusion F protein, which is the shape that the protein takes after the virus enters the cell. The prefusion F protein is also similar in both RSV-A and RSV-B subtypes, which are the two main strains of the virus.
These vaccines are at different stages of development and testing, and some of them may be available in the near future. They may offer different advantages and disadvantages over the existing vaccines, such as efficacy, safety, cost, availability, and administration.
Arexvy and Abrysvo are groundbreaking vaccines that offer a new way to prevent serious complications from RSV infection in older adults and infants. They are a major breakthrough that could save thousands of lives and reduce the burden of RSV on the health care system. If you are 60 years or older, talk to your health care provider about getting vaccinated with Arexvy. If you are pregnant, talk to your health care provider about getting vaccinated with Abrysvo. Together, we can protect ourselves and our loved ones from this deadly virus.
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