Maternal vaccination effective against infant severe RSV infection

28th April 2023

Maternal vaccination with a single dose against RSV gave rise to a high efficacy against severe infection among infants

RSV infection leads to a global high morbidity and mortality burden in children aged 0-60 months. Moreover, the greatest risk for hospitalisation occurs during the first 6 months of life. In a recent study, RSV-associated acute respiratory infection, led to the hospitalisation of one in every 56 healthy term-born infants. Whether maternal vaccination can reduce such RSV-related infection in newborns and infants remains uncertain.

In the present, randomised, double-blind, phase 3 trial, pregnant women received a single dose vaccine or placebo, between weeks 24 and 36. The two primary efficacy endpoints were severe RSV-associated lower respiratory tract illness and medically attended, less severe illness. Assessment of these outcomes took place at 90 and 180 days after birth. A lower boundary of the confidence interval > 20% was the success criterion for vaccine efficacy. 

Maternal vaccination and RSV-associated infections

Overall, 7358 women received either the vaccine (3682) or placebo. There were 6 cases of severe RSV in the vaccinated group and 33 in the placebo arm within 90 days of birth (vaccine efficacy = 81.8% 99.5% CI 40.6% – 96.3%). Within 180 days, the vaccine efficacy against severe infection was 69.4% (97.58% CI 44.3 – 84.1%). In contrast, vaccine efficacy was only 57.1% (99.5% CI 14.7 – 79.8) against less severe disease and did not meet the criteria for success.

Adverse events were similar in all groups within 1 month after injection or within 1 month after birth.

Higher exposure to particulate matter among infants increases all-cause and infection-related ED visits

10th March 2023

Greater particulate matter exposure during the first year of life is linked to higher all-cause and infection-related visits to the ED

Work by researchers from San Diego, La Jolla in the US, has shown that an increased exposure to particulate matter 2.5 μm or less in diameter (PM2.5), increases the risk for all-cause and infection-related visits to an emergency department among infants during their first year of life.

It has been recognised for several years that particulate matter comprising particles with a diameter of less than 2.5 micrometres, can penetrate deeply into the lungs, causing irritation and corrosion of the alveolar wall and therefore impairing lung function. PM2.5 comes from a wide range of sources including natural (i.e., dust, sea salt), anthropogenic emissions, e.g., vehicles, as well as household wood burning and from industry. The composition of PM2.5 is a complex mix of inorganic components such as heavy metals, organics (polycyclic aromatic hydrocarbons) and biologicals e.g., bacteria, viruses and fungi. Prior studies have shown that exposure to PM2.5 during pregnancy can increase adverse outcomes and stillbirth and early childhood exposure to air pollutants may play a role in the development of asthma. However, research to data on the impact of early PM2.5 exposure and the risk of hospitalisation during infancy is conflicting, indicating either an increased risk of bronchiolitis or no noticeable effect compared to older children.

In the current study, researchers examined all live births in California between 2014 and 2018 and estimated weekly exposure to particular matter based on the postal (zip) codes using a machine learning model. They set the outcomes of interest as both the first all-cause emergency department (ED) visit and the first infection-related visit based on birth status (pre or full-term).

Particulate matter and ED visits

A total of 983,700 infants, (49.4% female) were included in the analysis.

During the first year of life, the odds of an ED visit for any cause was higher for both pre-term (odds ratio, OR = 1.05, 95% CI 1.04 – 1.06) and full-term infants (OR = 1.05, 95% CI 1.04 – 1.05) for each 5-μg/m3 increase in exposure to PM2.5.

Similarly, there were elevated odds for a respiratory infection-related ED visit, pre-term (OR = 1.03) and full-term (OR = 1.05). In fact, the highest risks for an ED in both types of infant occurred between 18 to 23 weeks.

The authors concluded these elevated risks associated with exposure to particulate matter, may have implications for minimising exposure to air pollution.

Citation
Teyton A et al. Exposure to Air Pollution and Emergency Department Visits During the First Year of Life Among Preterm and Full-term Infants. JAMA Netw Open 2023

Nirsevimab approved for RSV in newborns and infants

15th November 2022

Nirsevimab, the first broadly protective option against respiratory syncytial virus (RSV) for newborns and infants, has received approval for use in Europe, the manufacturer AstraZeneca has announced.

The vaccine, which has the brand name Beyfortus, has been approved by the European Commission for the prevention of RSV lower respiratory tract disease in newborns and infants during their first RSV season.

The product represents the first and only single-dose RSV passive immunisation for the broad infant population, including those born healthy, at term or preterm, or with specific health conditions.

Approximately two-thirds of infants are infected with RSV during the first year of life, and 90% have been infected one or more times by two years of age. Moreover, the rate of hospitalisation for primary infection is approximately 0.5% but can be as high as 25%.

Produced by a collaborative effort from AstraZeneca and Sanofi, the terms of which were agreed in 2017, AstraZeneca leads all development and manufacturing activities for nirsevimab, and Sanofi leads commercialisation activities and records revenue.

Nirsevimab is a long-acting, antiviral monoclonal antibody which binds to the RSV F (fusion) protein and effectively locks the protein into the pre-fusion conformation and thus inhibiting entry of free virions into cells, as well as inhibiting spread of cell-associated virus by cell fusion. The drug is designed for all infants for protection against RSV disease from birth through their first RSV season with a single dose.

Nirsevimab clinical efficacy

In a phase IIb trial, infants were randomised in a 2:1 ratio to receive nirsevimab, at a dose of 50mg in a single intramuscular injection, or placebo at the start of an RSV season. The results showed that the incidence of medically attended RSV-associated lower respiratory tract infection was 70.1% lower with nirsevimab prophylaxis compared to placebo.

Further data came in a second trial in which infants who had been born at a gestational age of at least 35 weeks to receive a single intramuscular injection of nirsevimab or placebo (in a 2:1 ratio) before the start of an RSV season. The primary efficacy end point was medically attended RSV-associated lower respiratory tract infection through 150 days after the injection.

Medically attended RSV-associated lower respiratory tract infection occurred in 1.2% of those given nirsevimab 5.0% in the placebo group, corresponding to an efficacy of 74.5% (95% CI 49.6 – 87.1, p < 0.001).

Moreover, hospitalisation for RSV-associated lower respiratory tract infection occurred in 0.6% of those given nirsevimab compared to 1.6% in the placebo group. However, this was associated with a lower efficacy (62.1%), and which was not significant (p = 0.07).

According to the EMA, nirsevimab should be given before the RSV season or as soon as possible after birth for those infants born during the RSV season.

EMA recommends nirsevimab to protect infants from RSV

27th September 2022

Nirsevimab is recommended by the EMA for prevention of respiratory syncytial virus in newborns and infants during their first RVS season

Nirsevimab has been recommended for a marketing authorisation in the European Union for the prevention of Respiratory Syncytial Virus (RSV) lower respiratory tract disease in newborn babies and infants during their first RSV season and when there is a risk of RSV infection in the community.

Respiratory syncytial virus (RSV) is a common cause of childhood infections and which usually causes mild, cold-like symptoms. However, RSV can give rise to lower respiratory infection such as bronchiolitis and is also a major cause of hospital admissions in young children.

In 2015, for example, it was estimated that globally, there were 33·1 million episodes of RSV which led to around 3·2 million hospital admissions and 59,600 in-hospital deaths in children younger than 5 years.

While there are a number of recognised risk factors for RSV in children including prematurity, low birth weight, maternal smoking and a history of atopy, other data has revealed that among children hospitalised with RSV, 79% were previously healthy.

Nirsevimab (brand name Beyfortus) a recombinant human monoclonal antibody with an extended half-life that binds the F1 and F2 subunits of the RSV fusion (F) protein at a highly conserved epitope, locking the RSV F protein in the pre-fusion conformation and blocking viral entry into the host cell.

In a study of 1453 preterm, healthy infants, a single 50 mg dose of nirsevimab administered before the RSV season gave rise to a 70.1% lower incidence of RSV infection and a 78.4% lower incidence of hospitalisation for RSV-associated infections over an 150-day period after administration of the dose.

Nirsevimab was supported through the EMA’s PRIority Medicines (PRIME) scheme, which provides early and enhanced scientific and regulatory support to promising new medicines that address unmet medical needs. Beyfortus was also evaluated under EMA’s accelerated assessment mechanism because prevention of RSV infection in all infants is considered to be of major public health interest.

Nirsevimab clinical efficacy

The effectiveness of the monoclonal antibody was evaluated in a randomised, double-blind, placebo-controlled trial in which infants with a gestational age of at least 35 weeks were given either a single 50 mg intramuscular injection of nirsevimab (or 100 mg if their weight was above 5 kg) or placebo in a 2:1 (nirsevimab: placebo) ratio.

The primary efficacy endpoint was medically attended RSV-associated lower respiratory tract infections through to 150 days after the injection. The secondary efficacy endpoint was hospitalisation due to RSV over the same time period. A total of 1,490 infants with a median age of 2.6 months (48.4% female) were enrolled in the trial.

The primary endpoint occurred in 1.2% of those receiving nirsevimab and 5% of those given a placebo injection, corresponding to an efficacy of 74.5% (p < 0.001) and the efficacy against hospitalisation for RSV was 62.1% (p = 0.07).

According to the EMA, the opinion of the Committee for Medicinal Products for Human Use (CHMP) is an intermediary step on Beyfortus’ path to patient access. This opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorisation and once granted, decisions about price and reimbursement will take place at the level of each Member State, taking into account the potential role/use of this medicine in the context of the national health system of that country.