There is a search for a connection between asthma and the respiratory syncytial virus
What vaccines do we need to protect against chronic respiratory syncytial parasites: The case of clesrovimab, a long-acting antibody candidate
How these infections affect children in the long run has aroused intense interest, given that 3 million children are hospitalized with respiratory syncytial parasites globally every year. For now, protection for at-risk children remains limited to two prophylactic antibody drugs, palivizumab and nirsevimab. And an RSV vaccine, approved in the United States in May, is for use only in those aged 60 or older. Once an infection occurs, “it’s one of the important human viral pathogens with no treatment”, says virologist Larry Anderson at Emory University in Atlanta, Georgia, who has studied RSV for nearly four decades.
clesrovimab is a long-Acting Antibody candidate from the pharmaceutical company Whitehouse Station, New Jersey. According to data presented at an RSV conference earlier this year, its drug provided up to 81% protection against RSV complications in initial clinical testing. The late stage trials are going on.
One problem was that this vaccine preparation procedure seemed to lock the viral particles into a structural state that can elicit antibodies that bind to the viral proteins reasonably well, but that were not up to the task of neutralizing infection. According to some studies, the immune complexes that could promote a damaging inflammatory response have been seen in the lung after immunization with the formalin-inactivated vaccine.
It took decades of investigation and debate before researchers clarified the various factors that coalesced to inflict such damage. “It was a perfect storm of events that created the vaccine-enhanced disease that was experienced by those children,” says Varga.
In parallel, the inactivated virus seemed to do a poor job of training killer T cells, which would normally go on to eradicate virus-infected cells in future encounters. There was a crucial gap in the antiviral defences due to the immunological lapse. However, the vaccine did elicit a potent reaction from a subset of helper T cells that subsequently recruited a drove of other immune cells during infection, which could elicit a potent — and damaging — inflammatory response in the lungs.
This includes the identification of a suitable antigen for eliciting a potent antibody response that can neutralize infection and prevent severe disease. RSV relies on a surface molecule known as the fusion (F) protein to bind to and penetrate host cells, and virologists quickly recognized this as a promising target. Some of the F vaccines are created equal. This protein fluidly transitions between a compact ‘pre-fusion’ and an extended ‘post-fusion’ structure. The pre-fusion form, which aids viral penetration of cell membranes, can be readily neutralized by antibody binding, making it an excellent target for vaccines. However, early RSV vaccines tended to elicit a response against the post-fusion conformation of the F protein, which is much more stable than the pre-fusion structure. The vaccines generally don’t work in a way that makes them effective in fighting infections. In the early 2010s researchers led by Barney Graham and Peter Kwong at the US National Institute of Allergy and Infectious Diseases in Baltimore, Maryland, made important progress in figuring out the structure of the pre-fusion F protein. The engineered versions have the same structure as the original. The resulting F variants could be used to trigger a much more potent neutralizing response3.
There is a lot of uncertainty about the safety of maternal vaccines. In February, the pharmaceutical firm GlaxoSmithKline (GSK) halted trials for its vaccine after observing modestly increased rates of premature births in women who had received the shot. Bont, who helped to analyse preterm-birth data, says it isn’t yet clear what caused these premature births and that they might ultimately be linked to non-trial-related factors. The safety profile of Pfizer’s conceptually similar RSVpreF vaccine seems to offer little cause for concern, although their pivotal trial did show a slight — but not statistically significant — increase in preterm births in the vaccinated cohort. Zar doesn’t think that there is a real concern with prematurity. But she also recognizes that mothers will want thorough reassurance of the safety of any vaccine, and postmarket surveillance will be needed to carefully monitor this risk in the general population.
After decades of disappointment, the arrival of two preventive therapies is a cause for celebration.
Unless you have had cancer or experienced an inflammatory disorder, chances are you have never taken an antibody drug. But Oliver DeLong, a healthy baby from Chicago, Illinois, probably received his first antibody therapy before he was even four months old.
The introduction of nirsevimab could change that. Because of a change to the amino acid sequence in the antibody’s backbone, nirsevimab can circulate in the body for an extended period of time, providing prolonged protection against the virus. The studies show that recipients have high levels of the molecule in their bloodstream for at least five months. This persistence allows palivizumab to be used without monthly top-up jabs. Phase III studies show that a single dose of srsevimab can help kids avoid the severe infections that can lead to hospitalization and even death.
Maternal vaccination against respiratory infections is routine in health-care systems, unlike the universal roll-out of anti-millecine drugs. The success of either approach may depend on the existing clinical infrastructure.
“Price and ambition will be key,” says Steve Cunningham, a paediatric respiratory-disease specialist at the University of Edinburgh, UK. “There’s going to be a big debate over the next year or two about which is the best coverage option.”
It’s not clear what the price will be. Michael Dunne is the head of development at the Bill and Melinda Gates Medical Research Institute in Cambridge, Massachusetts, and he believes that it will be well below the $300 or more charged by pharmaceutical companies in Europe and North America. “We’re going to get the price down as low as we can,” Dunne says.
Palivizumab for Lower-Dependent Children: A Comparative Study in Nunavik and York University, and Prospects for a Universal Treatment of RSV
For more than a decade, Banerji has advocated for unrestricted access to palivizumab for Inuit babies born in remote northern communities, irrespective of gestational age. Her appeals have not gotten much traction.
Things should be different with nirsevimab. In a modelling study conducted by researchers at York University, it was found that nirsevimab should streamline the administration process and be cost-effective as compared to the pilot strategy in Nunavik.
Of course, it doesn’t have to be one or the other. Offering both strategies could achieve maximal population coverage, because of the different health-care systems and public acceptance of medical interventions in different countries.
Bont has worked with pharmaceutical companies to evaluate most of the RSV vaccines that are being considered for widespread roll-out as chair of the non-profit ReSviNET Foundation. The two strategies have never been tested against each other, but he believes that theImmune is better and possibly safer.
Both the Adimab agent and the nirsevimab are similar to each other. The antibodies bind to adjacent sites on the RSV fusion protein, and they demonstrate comparable potency in laboratory experiments, according to Laura Walker, former head of antibody sciences at Adimab. She says that the differences are minor. An important potential advantage has been found in RSM01. The Gates Foundation is planning to give the drug to low- and middle-income countries for as little as possible.
Children such as Oliver will likely be the first beneficiaries of nirsevimab, since they are in wealthier parts of the world.
She spoke to many parents who had their babies survive anRSV infection and continued to experience long-term effects, such as asthma. “The children just seem more susceptible.”
A mom remembers the morning of February 5, 2010, when Alexander was rescued from the hospital room by respiratory syncytial virus (RSV)
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It has been more than a decade, but there is still someone who remembers the early hours of February 5, 2010, as if it was yesterday. She was standing against the wall in a hospital room in Kent, UK, watching a team of doctors fighting to save her 13-week-old child, Alexander. She says that they were putting tubes in him. “I remember thinking: ‘It must be really bad if the doctors are crying.’”
At the hospital, doctors worked furiously to save Alexander, but stopped after 2.5 hours of trying to revive him. I held on to him while they turned off the machines. I sang to him because I didn’t want him to be scared,” she recalls.
When the post-mortem results came through three weeks later, Thomas discovered that Alexander had been killed by the respiratory syncytial virus. The virus causes a highly contagious infection of the lungs and respiratory tract. It can happen at any age but young children are most at risk. In most instances, the virus passes with minimal consequences after a week or two. Some children, especially those younger than six months, who have an underlying illness or who were born premature, can suffer serious consequences from RSV.
When these symptoms persist for weeks, months or even years, the question is if they are a disease or not. Scientists are unsure about how much of a credence to give to the idea of longRSV.
Source: The search for a connection between RSV and asthma
Theoretical Analysis of the Recent Developments in Palizumab for Low-Income Countries and Opportunities for Treatment of Disabled Populations
“That made us think that we should include long-term follow-up in our studies,” he says. The research really began after the market for palivizumab opened.
We are pleased to acknowledge the financial support of Moderna in producing this Outlook. Nature has sole responsibility for all editorial content.
Even as the developments engender optimism, substantial hurdles remain. Access to existing RSV interventions is already unequal, leaving people in low-income countries especially vulnerable. Without policies in place to ensure equity, these communities could be left exposed despite the recent progress.
Efforts to prevent infections and keep vulnerable people out of hospital are starting to pay off, but that doesn’t make them easy to deploy.
Researchers at the University of Wisconsin-Madison have found that a vaccine for the lung infection RSV can elicit a potent response from helper T cells that recruit other immune cells during infection. The vaccine, developed by the UW-Madison, appears to be effective against coronavirus but not against the other strains. It is currently being tested as an emergency backup for children aged 3 years and above.