The burden of respiratory syncytial virus and the need for a vaccine
This story is the first in a series about respiratory syncytial virus vaccines. Here we describe the disease itself, and in the next section we will describe the steps towards producing the first safe and effective vaccines.
The success of COVID-19 vaccines has rekindled enthusiasm for finding vaccines targeting diseases that have plagued us for many decades. In this series, we are going to discuss respiratory syncytial virus as a disease and why a vaccine is so necessary. In the next section, we will describe new research that brings us much closer to the successful production of the first safe and effective vaccines against respiratory syncytial virus.
Respiratory syncytial virus is a highly contagious disease that causes severe respiratory disease in young children, the elderly, and immunocompromised people. It is one of the leading causes of infant death worldwide, and a safe vaccine has yet to be approved for use. Also, the only drug approved to prevent infection is only effective for a short time. That could change soon with new discoveries about what went wrong with the very first vaccines and new insights into the structure of the virus that show a way forward.
Killing an average of more than 100,000 children worldwide each year, respiratory syncytial virus (RSV) is the second leading cause of death from a single pathogen in children under the age of one, behind only malaria. Developing countries experience twice the incidence of severe disease as developed countries and account for a staggering 99% of total RSV deaths worldwide. This appalling disparity is partly due to the lack of resources to provide basic supportive care, which is why a reliable vaccine that provides long-lasting protection against this dangerous respiratory pathogen would make a significant difference in alleviating global mortality.
Even in high-income countries like the United States, respiratory syncytial virus persists as a serious health burden, as it is the leading cause of hospitalization for children under five. As Jha et al. According to reports from Imperial College’s Respiratory Sciences, National Heart and Lung Institute, 50% of these hospitalizations occur in children younger than 6 months, showing how infants in their first months of life are particularly ill-equipped to fight the virus. 10% of cases in children under five require hospitalization, and risk factors such as low birth weight, prematurity, and congenital lung or heart disease lead to much higher hospitalization rates. For older, healthy people, RSV can present as mild upper respiratory infection symptoms, such as runny nose, sneezing, and coughing. But in more severe cases, it presents as a serious lower respiratory tract infection requiring hospitalization and mechanical ventilation, often in the form of bronchiolitis or pneumonia.
Elderly and immunocompromised people are also at additional risk of serious illness from RSV. Posted in the Journal of Infectious Diseases, Moyes et al. found that HIV-infected children were 3.5 times more likely to be hospitalized with RSV acute respiratory infection. Since respiratory syncytial virus infects approximately all children by age three and 60-70% within the first year of life, virtually all immunocompromised children are at risk. However, it doesn’t stop there. Since natural immunity against RSV infection does not last beyond a few months, older children and adults continue to be reinfected throughout their lives. Although not a threat to most healthy adults, those undergoing chemotherapy, organ transplants, or who have underlying conditions such as chronic heart and lung disease run a greater risk of serious health effects. Because the virus is so widespread, it is believed to have a negative impact on the health of older people comparable to the flu.
The frequency of respiratory syncytial virus infections is seasonal, at least in temperate regions, and infections are much more common during the colder winter months. This adds to the higher burden hospitals face during the winter months, straining healthcare systems and increasing the chances of co-infection with other respiratory viruses such as the common flu.
Discovered and initially characterized from a colony of chimpanzees in 1956 and later isolated from several infants, respiratory syncytial virus got its name because it causes cells to fuse, creating a multinucleated syncytium or giant cell containing multiple nucleases. Similar to other respiratory viruses such as COVID-19, infection begins with contact with respiratory droplets in the eyes or nose. Its spread is encouraged by the prolonged survival rate of virus particles on skin, clothing and other surfaces.
Currently, treatment for RSV consists of monoclonal antibodies. Created by cloning white blood cells, monoclonal antibodies work by binding to a specific part of the antigen targeted by the antibody. However, monoclonal antibody therapy is only available in limited circumstances and must be administered intravenously monthly, making it an impractical and expensive universal treatment. Palivizumab, the only monoclonal antibody licensed for the prevention of severe respiratory syncytial virus infections, is licensed only in high-risk infants and often needs to be given five times per high-incidence winter season. An accessible, safe and reliable preventive treatment, a vaccine, is absolutely necessary. Respiratory syncytial virus has posed obstacles to technology that has succeeded in producing other working vaccines, and a failed vaccine trial with a tragic outcome more than 50 years ago cast a shadow over new research for many years. Until recently, that is.
An effective respiratory syncytial virus vaccine must provide greater immunity than that provided by natural infection without causing any of the harmful effects seen in the first vaccine trial in 1965. The answer lies in a better understanding of the structure of RSV, and recent research has provided serious reason for hope. In the next section, we’ll tell you about the challenges faced by respiratory syncytial virus structural proteins, explaining the disastrous 1965 vaccine trial, and how there are now promising vaccine candidates on the horizon. .