Vaccines could offer new hope against respiratory syncytial virus
An affordable vaccine for all infants is the key to preventing and treating RSV in the Inuit population, but does not eliminate the epidemic burden?
This affordability could pave the way for administration of protective antibodies to all infants, regardless of geography, health status or whether babies were born preterm. Anna Banerji is an infectious-disease specialist at the Dalla Lana School of Public Health in Canada and she studies the well- being of Inuit children, a population with some of the highest rates of vaccine- related deaths.
Prevention is also on the horizon. Even if the highest risk from RSV comes in the earliest months of life, severe disease can still occur in the year or two that immediately follows. Moderna’s vaccine that has already proved effective in older adults is one of several vaccine candidates targeted at protecting toddlers.
If we are truly committed to reconciliation, then things need to change. If we can make progress on this, then it shows the rest of the world that the pernicious burden of health disparity shouldered by Indigenous people is not unsolvable. We just need to act.
Clenserovimab: An Effective Antidote for Vaccine-Enhanced Influenza in the Lung
There are prophylactic antibodies that are already approved for use against these infections. Since 1998, palivizumab has been used to prevent RDSV in high risk babies. The drug strategy has never been used on a large scale.
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. A number of studies have suggested that after immunization with the vaccine, the anti-RSV IgG fragments in the lungs could become immune complexes, causing a damaging inflammatory response.
Fortunately, subsequent instances of vaccine-enhanced disease have been exceedingly rare. It’s better to intercept such outcomes before they arise in humans than before, according to an infectious-disease paediatrician in the Netherlands. In the 1960s we thought we could make a vaccine for everything in a day. “The preclinical and early clinical development pathway is much more regulated today.”
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. That immunological lapse left a crucial gap in the antiviral defences. 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.
clesrovimab has a number of design features that make it distinct from nirsevimab. One key difference is its target location. Nirsevimab binds to a spot on the protein’s apex — one that is only present in the protein’s pre-activation state, before it undergoes a structural change necessary for viral entry into host cells. There is an area that remains consistent across the different sections of theProtein but clesrovimab is on the flank.
To protect an infant from damage, you can give them a single shot of this highly potent antidote, and it will be effective for the entire season. The company is working with a French pharmaceutical firm on the drug.
After decades of disappointment, the arrival of two effective preventive therapies is clearly a cause for celebration — but unanswered questions remain.
There is some uncertainty around safety for 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 said that it was not yet known what caused these premature births and that they could be linked to non-trial related factors. The safety profile of the vaccine appears to offer little cause for concern, despite a slight increase in premature births in the vaccine group in the pivotal trial. “I personally don’t think that there is a real concern with prematurity,” says Zar. 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.
If you have ever been affected by an inflammatory disorder or have had cancer, then you’ve probably never taken an antibody drug. Oliver DeLong is a baby from Chicago, Illinois, who probably received his first therapy before he was even a year old.
The widespread use of drugs against respiratory infections by health-care systems is different from the practice of maternal vaccinations against respiratory infections. And the successful adoption of either immunization approach might hinge crucially on the existing clinical infrastructure.
Steve Cunningham is a 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.”
Health authorities in one part of the Canadian Arctic — in the Nunavik region of northern Quebec — launched a pilot programme in 2016 in which they expanded eligibility for palivizumab from high-risk babies to include healthy, full-term newborns. The programme was stopped in four years because of limited health care resources and a lack of cost-effectiveness.
Things should be different with nirsevimab. As a one-time, lower-cost option, nirsevimab should streamline the administration process, while also being “highly cost-effective or cost-saving as compared to the pilot strategy in Nunavik”, according to a 2021 modelling study led by researchers at York University in Toronto5.
If disease prevention were the only consideration, then — shot for shot — antibodies would be the better option, says Louis Bont, a paediatric infectious-disease specialist at University Medical Center Utrecht in the Netherlands.
In the past, Bont’s work with pharmaceutical companies has included evaluating some of the vaccine candidates being considered for widespread roll-out. The two strategies haven’t been tested in a head-to-head environment, but his opinion is that the antibody may be more effective and potentially safer.
Those born prematurely to immunized women might be insufficiently protected because they will acquire fewer maternal antibodies in the womb than would babies who were born at full term. The baby born a few months before theRSV season may have lost most of their immunity by the time they are exposed to the disease. Antibodies, by comparison, can always be given right before or during an active RSV season. They can be administered in a hospital maternity ward or at an early paediatrician visit, instead of relying on pregnant people to seek out vaccinations when they are in the second to third trimester.
The Price of Nirsevimab for Low-Income Countries and Children’s Health: Recent Developments in the 21st Century
It’s not known what that price will be. Michael Dunne, the chief medical officer and head of development at the Bill & Melinda Gates Medical Research Institute in Cambridge, Massachusetts, believes that it will be well below the $300 or more that drug companies will charge in Europe and North America. Dunne said that the price would be brought down as low as possible.
As with most medical interventions, however, the first beneficiaries of nirsevimab will invariably be in wealthier parts of the world — that is, children such as Oliver.
Two years ago, when the toddler was four months old, his family members who later tested positive for Rsv coddled him at his first Thanksgiving dinner. Oliver could have been the one who didn’t contract the virus.
We are pleased to acknowledge the financial support of Moderna in producing this Outlook. As always, Nature retains sole responsibility for all editorial content.
Studies are starting to uncover a connection between infections and respiratory problems in later life, such as wheezing and asthma, according to research. Other research is trying to find out how other diseases can work together or compete with Reynolds Spry.
These developments do engender optimism but there are still a lot of hurdles. 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 beginning to pay off, but deploying these strategies presents new challenges.
Researchers have suggested that Moderna’s RSV vaccine might create an inflammatory response in lungs after immunization. They claimed that the anti-RSV IgG fragments may become immune complexes that could trigger a damaging inflammatory response in the lungs. However, Moderna’s vaccine had a potent reaction from a subset of helper T cells that subsequently recruited a drove of other immune cells during infection.