Age-dependent RSV asthma risk creates vaccine conundrum


By Michael Woodhead

6 Dec 2018

The risk of asthma linked to infant RSV infection is much greater if a child acquires the infection later in infancy, NSW researchers have shown.

Children who contract severe RSV disease after the age of six months are more than twice as likely to develop severe asthma in later years than babies who get the disease prior to six months, a study from the University of NSW has found.

The lower asthma risk associated with early RSV infection may be due to transient protection conferred by maternal antibodies and could have implications for the scheduling of RSV vaccines, say respiratory specialists at the Royal Children’s Hospital, Sydney.

In a study published in the Journal of Infectious Diseases, they report on risks of asthma for 18,042 children with severe RSV disease who were hospitalised in their first two years of life in NSW between 2001 and 2010.

There were 1374 children who subsequently developed asthma after the age of two, and rates were related to the age of first RSV infection. The incidence/1000 child-years of asthma hospitalisation was 0.5 for children who had RSV before the age of three months, 0.9 for RSV infection at 3-6 months, 2.0 for RSV infection at 6 -12 months and 1.7 for RSV infection at 12 to 24 months.

Study lead author Dr Nusrat Homaira from UNSW’s School of Women’s and Children’s Health said it was notable that 60% of all RSV admissions were for infants aged six months or younger.

“This confirmed that there is a very good reason to develop the maternal vaccine, because it is going to protect them in the first six months of their life,” she said.

But for the 40% of children hospitalised with RSV after the age of six months, the risk of asthma was two to four times higher than those who had RSV at a younger age.

“So what our analysis showed is that even though you get more RSV in the first six months of life, if you get severe RSV after six months of age, the rate of subsequent asthma is actually higher in those children.”

Dr Homaira and colleagues postulated that the lower asthma risk seen with early RSV infection might be because infant lungs are protected by maternal antibodies, whose levels wane after about six months.

“The first six months of life is also the time for rapid lung alveolar multiplication and airway remodelling thus it could be that alteration to the lower airway due to severe RSV disease in the first six months of life is transient and improves as the pathogen clears,” they wrote.

“On the other hand, lung alveolarisation is completed by ages 2−3 years and therefore, it is possible that severe RSV disease beyond infancy is associated with disruption of alevolarisation process leading to persistent adverse impact on lung development and function.”

They said their findings had important implications for the 10 RSV vaccines currently in development, and particularly the maternal vaccine for third trimester use now undergoing phase 3 clinical trials.

A ‘passive’ RSV vaccine administered to an expectant mother may only protect as far as six months into the baby’s life, after which time the infant could still develop an RSV infection.

“While the maternal vaccine is extremely important for our children, we also need an active vaccination strategy or an active vaccine candidate that is going to protect children in the first two years of life,” said Dr Homaira.

“Our data suggest that an effective vaccine for older children aged over 6 months will have a beneficial impact on the long−term [asthma] consequences of RSV disease as well,” the study authors concluded.

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