The first vaccine to prevent severe lung infections, including pneumonia, in infants will save thousands of lives and reduce the burden on health systems of low- to middle-income countries, researchers say.
A vaccine for Respiratory Syncytial Virus (RSV) has been elusive ever since the virus was first reported in 1956. Decades later, researchers now have a vaccine that in late-stage clinical trials has shown to be safe and almost 82% effective in preventing severe lower respiratory tract illness (LRTI) in infants in the first 90 days of life, when given to their mothers in the second half of pregnancy.
Vaccination of the mother induces protective antibodies, which are transferred over to their foetuses in utero.
The shot was also 69.4% effective in preventing severe infections in the first six months. It however did not meet a secondary endpoint, or goal, of reducing non-severe illness in infants.
The vaccine is currently under review by regulatory authorities in the United States and Europe.
RSV is a common virus that can cause respiratory infections, particularly in young children and older adults. It is the most common cause of bronchiolitis (inflammation of the small airways in the lung) and pneumonia in children under one year in South Africa. When an adult gets RSV infection, they usually have mild cold symptoms, but some may develop pneumonia and other lung infections.
Part of study conducted in SA
The final results of the single-dose Pfizer vaccine study (called MATISSE) were published in the New England Journal of Medicine (NEJM) earlier this month after researchers stopped the Phase 3 double-blind trial early because of the vaccine's high efficacy. The trial was conducted in 18 countries, including South Africa.
Professor Shabir Madhi, head of Vaccinology at the University of the Witwatersrand and co-author of the study says RSV is the leading cause of LRTI among children in all countries. "It causes over 40% of all LRTI hospitalisations in children under 5 years and as many as 70% of hospitalisations during the annual RSV peak season (winter)."
Globally RSV causes 34 million LRTIs, 3.4 million hospitalisations, and 60 000 to 199 000 deaths every year. Almost all these deaths (99%) are in children in low- and middle-income countries with 50% residing in Africa. That's according to a Lancet systematic review and meta-analysis on the global burden of acute respiratory infections due to RSV in young children.
"This leads to a huge drain on resources in paediatric facilities across the globe. The vaccine has tremendous value in that it can reduce by 82% the risk of RSV in newborns but it also reduces pressure on health services," Madhi says.
RSV burden in South Africa
Dr Jocelyn Moyes, an epidemiologist at the National Institute of Communicable Diseases (NICD), describes the results as "very exciting". She says about 96 000 children under 5 years in South Africa have severe RSV illness every year, of which 27 982 cases occur in children younger than 2 months of age. Approximately 6 804 per 100 000 children (age 1 and 2 months) will be admitted to hospital each year with RSV lower respiratory tract infection.
She tells Spotlight that most children will have RSV in the first year of life and many will experience more than one infection in the first 5 years of life. She says approximately 650 children die each year from RSV, with 200 of these occurring in the young infants (under 2 months).
"RSV is ubiquitous, so occurs in all provinces. It is the very young child (< 3 months) who is at the highest risk of being admitted to hospital with rates of hospitalisation dropping down to 1 000 per 100 000 in the 11-month age group," she says.
The virus spreads through droplets when an infected person coughs or sneezes or by touching contaminated surfaces. Symptoms of RSV include a runny nose, coughing, sneezing, fever, and difficulty breathing. In most cases, RSV causes mild cold-like symptoms, but it can lead to more severe infections.
Moyes says RSV circulates all year round in South Africa but there is a season of higher circulation starting in February, peaking in late April and dropping off in May. "So, just before the start of the influenza season in June. There is no evidence that the season is different across the provinces.
Regulatory approval
According to Willis Angira, Pfizer's Communications Manager for East and Southern Africa, the Food and Drug Administration (FDA) in the United States and the European Medicines Agency (EMA) are currently reviewing the data and results from the trial with a view to licensure.
A costing study at sentinel sites across South Africa was conducted to estimate out-of-pocket and indirect costs for Respiratory Syncytial Virus (RSV)-associated mild and severe illness. Click on the link provided to access the results: https://t.co/2BV3VNnB6Z
-- NICD (@nicd_sa) April 14, 2023
Both regulatory authorities are also evaluating the single-dose vaccine for people ages 60 and above. Pfizer's data suggests the vaccine reduced the risk of RSV-related illness for older adults by 67% to 86%.
The company has not yet filed for regulatory approval in South Africa.
Mahdi said in a tweet on April 6: "The challenge is for rapid licensure and access where it is required most - in low- and middle-income countries. (We) cannot allow for (the) recent history of a 10-20 year lag of introduction of life-saving vaccines in LMICs compared with (the) introduction in high-income countries. There is (a) moral responsibility on pharma to license vaccine in LMIC at affordable price (price tiering). Equally so, governments in LMIC need to act to protect children in their countries by funding and deploying the vaccine timeously."
Angira says immunisation of pregnant mothers to help protect young infants is also an important strategy to combat other common infant diseases such as neonatal tetanus, diphtheria, and pertussis.
What is available?
As there is no approved vaccine yet, a monoclonal antibody injection called Palivizumab is occasionally used to help prevent RSV in children under 24 months who are at high risk for getting RSV.
Madhi says, at $1 000 a dose, (more than R18 000 per dose as of April 18), the price of the treatment is mostly prohibitive for low- to middle-income countries (LMIC). Two doses are needed and the injection needs to start before the season amounting to $4 000 to $5 000 per child.
"For this reason, it never gained traction - had limited use for high-risk individuals (for example, pre-term newborns) and for high-income countries," Madhi says.
He says as with the pneumococcal conjugate vaccine where there is price differentiation for the vaccine ($160 a dose for high-income countries and $20 a dose for LMIC) he expects Pfizer, who have not yet announced a price, to come in at less than $10 a dose for their RSV vaccine. "That would be reasonable," he says.
Sign up for free AllAfrica Newsletters
Get the latest in African news delivered straight to your inbox
The RSV pipeline
There are several different prevention technologies in the pipeline besides vaccinating pregnant mothers who will then pass on antibodies to their infant. The second technology is a monoclonal antibody treatment which would be given as passive immunity to the young infant shortly after birth. The child is given the antibodies via injection rather than producing them through their own immune system.
There are also infant vaccines being developed.
In the same edition of the NEJM, researchers published results of a single-dose, long-acting monoclonal antibody injection called Nirsevimab, which reduced severe risk of hospitalisation in children due to RSV by 76%.
Nirsevimab is designed to protect infants entering or during their first RSV season and for children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season.
In a statement the developers say Nirsevimab has been developed to offer newborns and infants direct RSV protection via an antibody. The developers of the treatment, Sanofi and AstraZeneca, have applied for FDA approval and a decision is expected in August.
Madhi says there are also some studies in the pipeline looking at the feasibility of vaccinating young children to protect against RSV once they are born. Recruiting has started for a phase 1 trial to test the safety and immunogenicity of a live attenuated intranasal vaccine to prevent RSV in children aged six to 36 months.
"It is important that we advocate for access to these technologies once they are licensed. We have a body of evidence ready, including the burden of RSV cost to the health care system and cost-effectiveness data that will assist policy makers making the decisions to implement these important technologies," says Moyes.
