The first vaccine to prevent severe lung infections, including pneumonia, in infants will save thousands of lives and reduce the burden on health systems in 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 to their foetuses.

The shot was also 69.4% effective in preventing severe infections in the first six months. However, it did not meet a secondary goal of reducing non-severe illness in infants.

The vaccine is currently under review by regulatory authorities in the US 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 South Africa

The final results of the single-dose Pfizer vaccine study (called MATISSE) were published in the New England Journal of Medicine (NEJM) 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 five years and as many as 70% of hospitalisations during the annual RSV peak season (winter).”

[caption id="attachment_1656059" align="alignnone" width="720"] © Provided by Daily MaverickA scanning electron micrograph of human respiratory syncytial virus virions (colourised blue), labelled with anti-RSV F protein/gold antibodies (yellow), shedding from the surface of human lung epithelial A549 cells. (Image: NIH / Spotlight)[/caption]

Globally RSV causes 34 million LRTIs, 3.4 million hospital admissions 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 of 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), says the results are “very exciting”. She says about 96,000 children under five years in South Africa have severe RSV illness every year, of which 27,982 cases occur in children younger than two months. About 6,804 per 100,000 children (age one and two 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 five years. About 650 children die each year from RSV, with 200 occurring in the young infants (under two months).

“RSV is ubiquitous, so it occurs in all provinces. It is the very young child (under months) who is at the highest risk of being admitted to hospital, with rates of hospitalisation dropping 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 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 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 US and the European Medicines Agency are reviewing the data and results from the trial with a view to licensure.

Both regulatory authorities are also evaluating the single-dose vaccine for people 60 and older. Pfizer’s data suggest 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.

[caption id="attachment_1656060" align="alignnone" width="720"] © Provided by Daily MaverickDean of the Faculty of Health Sciences at Wits University, Professor Shabir Madi. (Photo: Wits University / Spotlight)[/caption]

Mahdi said in a tweet on 6 April: “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- to 20-year lag [in the] 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?

Since 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 that, 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. Two doses are needed and the injection needs to start before the season, amounting to $4,000 to $5,000 per child.

Read more in Daily Maverick: New pneumonia vaccine to potentially save thousands of children from death

“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 that, as with the pneumococcal conjugate vaccine where there is price differentiation for the vaccine ($160 a dose for high-income countries and $20 for LMIC), he expects Pfizer, which has not yet announced a price, to come in at less than $10 a dose for their RSV vaccine. “That would be reasonable.”

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 hospital admission 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 who remain vulnerable to severe RSV disease through their second RSV season.

Read more in Daily Maverick: As with Covid-19, the effects of TB can linger long after it is cured

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-one 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 healthcare system and cost-effectiveness data that will assist policymakers making the decisions to implement these important technologies,” says Moyes. DM/MC

This article was published by Spotlight – health journalism in the public interest.