Needle free nasal vaccine blocks whooping cough infection

A research team in Dublin believes it has found a way to stop whooping cough not only from making people sick, but from spreading quietly through communities at all.

Whooping cough, or pertussis, is a serious infection caused by the bacterium Bordetella pertussis. Modern vaccines have saved many infants from severe disease. Yet outbreaks still occur in countries with high vaccine coverage, and the illness continues to circle back every few years.

The problem lies in where protection starts and ends. Current acellular pertussis shots, the ones many children receive, work well at preventing severe symptoms in the lungs. However, they do not fully block the bacteria from settling in the nose and throat. That means a vaccinated person may feel fine but still carry and spread the infection to others, including newborns who are too young to be fully protected.

That gap has frustrated scientists and public health officials for years. It has also created a clear demand for next generation vaccines that protect the airway itself and cut off transmission.

Researchers at Trinity College Dublin, led by Professor Kingston Mills and Dr Davoud Jazayeri, have taken a different approach. Their work, published in Nature Microbiology, describes a nasally delivered vaccine built from antibiotic inactivated Bordetella pertussis, known as AIBP.

Instead of relying on an injection into muscle, the vaccine is sprayed into the nose, directly onto the mucosal surfaces where the bacteria first land. “We’ve applied our understanding of protective immune pathways to engineer a fundamentally different kind of vaccine,” Mills said.

The team used a strong antibiotic to kill the bacteria in the lab while keeping their outer structure intact. Those inactivated cells cannot cause infection, but they still look “real” to the immune system. When given as a nasal dose, they trigger local defenses in the airway rather than only in the bloodstream.

“By stimulating immunity where infections begin, at the respiratory mucosa, we can offer stronger protection and potentially interrupt community transmission,” Mills said.

To create AIBP, the scientists grew Bordetella pertussis, then treated it with the antibiotic ciprofloxacin at levels high enough to block DNA replication and kill all the bacteria within hours. Tests showed no survivors, yet the bacterial shells stayed intact.

Those shells hold the proteins and surface molecules that immune cells recognize. When the vaccine is given intranasally or by aerosol, dendritic cells in the nose and lungs pick up the inactivated bacteria and switch into an activated state. They display pieces of the pathogen to T cells and release signals that guide a strong, targeted response.

In preclinical models, this process drove a powerful T cell response in the airway, especially Th1 and Th17 cells that are known to fight bacterial invaders. Crucially, many of these T cells became tissue resident memory cells. They settled in the lining of the nose and lungs and stayed there as long term sentinels.

Local antibodies also rose. The vaccinated animals produced IgA in their nasal passages, which helps trap and neutralize bacteria at the surface. Blood antibodies, mainly IgG, increased as well, although the local response appeared to matter most for blocking colonization.

When the researchers challenged vaccinated animals with live Bordetella pertussis, the results stood out. A single nasal or aerosol dose of AIBP gave strong protection in the lungs. Two doses cleared bacteria from lung tissue and from the nasal cavity, something current acellular vaccines fail to do.

In animals that received standard acellular shots under the skin, the lungs were largely protected from severe disease, but the nose remained colonized. Those animals could still carry and potentially spread the bacteria. In contrast, AIBP cut bacterial counts to zero in both the lower and upper respiratory tract within weeks.

The protection lasted. Months after vaccination, tissue resident T cells were still present in the airway. When exposed again to live bacteria, those animals cleared the infection much faster than unvaccinated controls.

The team also tested AIBP as a booster for animals that had already received conventional acellular vaccines. Prior shots did not block the new response. After a mucosal AIBP boost, those animals developed the same strong local immunity and cleared infection from both lungs and nose.

The Trinity group sees the AIBP design as more than a one off product. Because the bacteria are inactivated by antibiotics instead of being genetically altered, the concept can, at least in theory, extend to other respiratory pathogens.

The authors suggest similar nasal vaccines could be built against Staphylococcus aureus, Streptococcus pneumoniae, Mycoplasma pneumoniae or even Mycobacterium tuberculosis. In each case, the idea is the same. Deliver an inactivated whole cell preparation to the airway, prompt strong local T cell responses and IgA, and aim for sterilizing immunity.

The platform is also needle free, which could help acceptance in children and adults. A spray or inhaled mist is often less intimidating than a syringe. It also suits large scale campaigns where staff may have limited training.

The research began with a Science Foundation Ireland Frontiers for the Future Award to Mills. It is now advancing within the ARC Hub for Therapeutics, a €32 million national translational initiative supported by Science Foundation Ireland and co funded by the Government of Ireland and the European Union.

If this mucosal pertussis vaccine works in humans as it does in preclinical studies, it could reshape how we manage whooping cough. By preventing bacteria from settling in the nose and throat, AIBP has the potential to block silent spread and protect infants who have not yet completed their primary shots. That shift from disease control to transmission control could reduce outbreaks and lower the overall burden of illness.

As a booster for people already vaccinated with older acellular shots, the new vaccine might restore strong protection in adolescents and adults and cut down on household spread to newborns. Because the bacteria are killed by antibiotics and do not replicate, the safety profile may be more acceptable than live attenuated nasal vaccines.

Beyond whooping cough, the platform suggests a broader path for respiratory vaccines. Needle free, airway targeted immunization could help stop other bacterial infections at the door rather than only softening symptoms. In low resource settings, simple intranasal delivery could make it easier to reach large populations.

On the research side, the work offers a template for designing mucosal vaccines that harness tissue resident memory T cells and IgA. That knowledge will be valuable for scientists tackling other respiratory diseases that continue to evade full control.

Research findings are available online in the journal Nature Microbiology.

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