Overview of RSV Vaccine

What is RSV?

Respiratory syncytial virus (RSV) belongs to the respiratory virus family and can cause respiratory infections in people of all ages throughout the year. It particularly poses a risk of severe infection and respiratory sequelae for pediatric patients, as well as for adults with immune deficiencies or underlying conditions. The RNA genome of RSV consists of 10 genes encoding 11 proteins. These proteins include two non-structural proteins (NS1 and NS2), four envelope proteins: attachment glycoprotein (G), fusion protein (F), matrix protein (M), and small hydrophobic protein (SH); and five nucleocapsid proteins: nucleoprotein (N), phosphoprotein (P), large RNA polymerase (L), M2-1 (zinc-binding transcription anti-termination factor), and M2-2 (regulatory factor involved in RNA replication and transcription balance). Regarding vaccine development, the most important protein is the F protein. The F protein in the viral envelope of RSV strains is highly conserved, making it an excellent potential vaccine target. The F protein has two conformations, pre-F and post-F. The surface of infectious RSV contains both conformations of the F protein, but after virus entry into cells, the pre-F conformation undergoes a transition to the post-F conformation, resulting in only the post-F conformation being present on the virus surface.

Respiratory syncytial virus (RSV) genome and virion structure. (Jenkins, V.A.; et al, 2023)

What is RSV Vaccine?

The RSV vaccine is a preventive measure against respiratory syncytial virus (RSV) infection, a common yet potentially serious viral infection. RSV typically poses significant health risks to infants and young children, particularly those with weakened immune systems or other health issues. The primary aim of this vaccine is to stimulate the immune system to produce antibodies, thereby reducing the risk of infection and the severity of related complications upon exposure to RSV. Although the development of the RSV vaccine has been underway for quite some time, there are still challenges in achieving a safe and effective vaccine.

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RSV Vaccine History

In 1957, American physician and virologist Robert M. Chanock isolated the respiratory syncytial virus (RSV) from infants with respiratory illness. It was later renamed human orthopneumovirus and human respiratory syncytial virus. In 1960, a research team developed a killed-virus vaccine by inactivating the virus with formalin and then preparing it into a vaccine with an aluminum adjuvant to enhance its immunogenicity. This vaccine was initially approved for infants. However, after its widespread use, it was discovered that many vaccinated infants did not have a reduced risk of illness compared to unvaccinated infants. The failure of the killed-virus RSV vaccine had a negative impact on RSV vaccine development. Subsequent attempts with purified F protein or recombinant F protein vaccines, some using vaccinia virus or bovine parainfluenza virus as vectors, also encountered similar issues and ended in failure. Throughout the 1960s, research into RSV vaccines persisted. Various vaccine platforms were explored, including live attenuated virus, cDNA (complementary DNA), viral vectors (such as poxviruses and adenoviruses), protein subunits (F protein, G protein), synthetic peptides, among others. Later developments included the exploration of recombinant nanoparticles and mRNA vaccines. In recent years, with the advancement of various types of RSV vaccines, there is renewed hope for the development of an effective RSV vaccine.

RSV Vaccine Types

Currently, the development of RSV vaccines primarily focuses on four main types: attenuated live vaccines, virus vector RSV vaccines, recombinant protein RSV vaccines, and mRNA RSV vaccines.

RSV mRNA Vaccines

The mRNA vaccine process involves several steps, including plasmid template construction and purification, mRNA synthesis and purification, liposome encapsulation and so on. The RSV mRNA vaccine is a new kind of vaccine developed to target respiratory syncytial virus (RSV). It uses mRNA technology, which is different from traditional vaccines. Essentially, this vaccine delivers mRNA containing specific instructions into human cells to prompt them to produce a protein related to RSV. When the body detects this protein, the immune system responds by creating antibodies to fight against RSV. Since RSV is a common respiratory virus, especially impacting infants and the elderly, the aim of this vaccine is to stimulate the body's immune system to recognize and combat RSV effectively, thereby reducing the occurrence of infection and associated illnesses. Research in the field of mRNA technology has made significant contributions to the development of COVID-19 vaccines. The contributions of mRNA technology are crucial for the development of vaccines in the event of infectious disease outbreaks and for cancer treatment. The successful application of mRNA technology in COVID-19 vaccines signifies a breakthrough in the field of conventional vaccines. Among them, a representative in the RSV vaccine field is mRNA-1345. mRNA-1345 is a monovalent mRNA RSV vaccine encoding the RSV fusion pre-F protein. It utilizes lipid nanoparticles (LNPs) similar to those used in the company's COVID-19 vaccine and contains optimized protein and codon sequences.

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Virus Vector RSV Vaccines

Currently, adenovirus vectors and poxvirus vectors are the main types of virus vectors used for RSV vaccines. Approved adenovirus vector COVID-19 vaccines have mature production processes. Virus vector RSV vaccines are a type of vaccine developed to target respiratory syncytial virus (RSV) using a viral vector approach. Unlike traditional vaccines, which may use weakened or inactivated forms of the virus, virus vector vaccines use a different virus, known as the vector, to deliver genetic material from RSV into the body. This genetic material then instructs the body's cells to produce proteins that trigger an immune response against RSV. These vaccines hold promise because they can stimulate a robust immune response while also being relatively easy to manufacture. However, their effectiveness and safety need to be thoroughly evaluated through clinical trials. Some examples of virus vector RSV vaccines include those based on adenovirus or modified vaccinia Ankara (MVA) vectors, which have shown potential in preclinical studies.

Attenuated Live Vaccines

Attenuated live vaccines are a type of vaccine created by weakening a virus or bacteria to the point where it can still induce an immune response in the body but cannot cause disease. These vaccines typically involve modifying the pathogen through processes such as serial passage in cell culture or genetic manipulation. When administered, attenuated live vaccines mimic natural infections, stimulating the immune system to produce antibodies and cellular immunity against the targeted pathogen. Since they closely resemble the actual infectious agent, they can generate a robust and long-lasting immune response. Attenuated live vaccines have been successfully used to immunize against various diseases, including measles, mumps, rubella, and chickenpox. However, they may not be suitable for individuals with weakened immune systems, as there is a small risk of the attenuated virus or bacteria causing illness in these individuals. Despite their efficacy, the production and storage of attenuated live vaccines can be more complex compared to other vaccine types. Additionally, there is always a slight possibility that the attenuated pathogen could revert to a virulent form, although this risk is extremely low.

Recombinant Protein RSV Vaccines

Recombinant protein RSV vaccines are a type of vaccine developed to combat respiratory syncytial virus (RSV) by using proteins produced through genetic engineering. These vaccines involve inserting genetic material encoding specific RSV proteins into host cells, such as yeast or mammalian cells, to produce large quantities of the desired proteins. Once the proteins are generated, they are purified and used as antigens in the vaccine formulation. When administered, the vaccine stimulates the immune system to recognize and mount a defense against RSV. Recombinant protein RSV vaccines offer several advantages, including precise control over antigen composition, scalability of production, and a well-established safety profile. They are particularly suitable for vulnerable populations, such as infants and the elderly, who may be at higher risk of severe RSV infection. Several recombinant protein RSV vaccines are currently in development, with some showing promising results in clinical trials. However, challenges remain in achieving optimal efficacy and durability of immune response, as well as ensuring affordability and accessibility of the vaccines, especially in low-resource settings.

Prospect of RSV Vaccine

Respiratory syncytial virus (RSV) is associated with approximately 3.4 million hospitalizations globally, with 175,000 involving children under the age of 5 in the United States alone. Regarding global mortality, deaths range between 95,000 and 150,000 individuals, with approximately 14,000 deaths among the adult population in the United States. The epidemiology of respiratory syncytial virus and its global disease burden underscore the necessity of preventive measures. Recently, two vaccines have been approved for active immunization against RSV, while multiple candidate vaccines are in development, including attenuated live vaccines or chimeric vaccines based on mRNA, subunits, and virus-like particles, as well as vaccines based on recombinant vectors. Based on positive results from clinical trials, it is anticipated that in the coming years, the approved preventive RSV vaccines will be expanded, and various new vaccines will enter clinical development stages.

Reference

1. Jenkins, V.A.; et al. The Quest for a Respiratory Syncytial Virus Vaccine for Older Adults: Thinking beyond the F Protein. Vaccines. 2023, 11(2): 382