14 January 2014

Nasal vaccine: towards an alternative to injection for infants

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Delivering a whooping cough and bronchiolitis vaccine through a single inhalation could become an alternative to traditional injections. However, such approach still requires fine tuning.

Whooping cough and bronchiolitis are respiratory infections frequently affecting young children. In particular, infants under three months are very sensitive to these illnesses, which can lead to death in the most severe cases. Today, more than 85% of children worldwide are vaccinated against whooping cough, using a conventional injection method. This involves, in the example of the French immunisation schedule, five shots to children spread between the time they are two months and 13 years of age. The trouble is that the immunity conferred by the vaccine decreases with time. As a result, whooping cough reappears harmlessly in young adults. These may, in turn, contaminate infants.

Before the age of six months, infants’ immune system is not mature enough to induce an efficient response to the vaccine. Unfortunately, this is a time when infants are most vulnerable to whooping cough. As for bronchiolitis, it is almost impossible to avoid and very contagious, while no vaccine is available. This led scientists from an EU-funded research project, called Child Innovac, to look for an alternative way of protecting infants

“We have assessed the efficiency of a nasal vaccine, in the form of a nasal spray,” says Camille Locht, a researcher at the Infection and Immunity Centre at the Lille Pasteur Institute, in France and the project coordinator. “It provokes a local immunity in the respiratory tract that prevents incoming bacteria from developing,” he tells youris.com. 

The team designed a vaccine made of live attenuated pertussis, the bacterium causing whooping cough. The project, which was completed in March 2012, involved a clinical trial in a group of selected adults. The results are due to be published in the online journal Plos One. “We noticed no side effect, and we were able to determine the right dose to inhale in order to make the attenuated bacteria colonise the respiratory tract and induce the immune response,” says Locht.

Prior to this trial, animal studies have shown that the vaccine has interesting positive side effects. Indeed, its anti-inflammatory action induces a protection against the virus responsible for a majority of bronchiolitis—the respiratory syncytial virus (RVS). This discovery, however, needs to be confirmed in humans.

Like with any new vaccines, some outstanding issues may first need to be resolved. Antibodies against whooping cough present in the mother, even in small quantities, and transmitted to the fœtus may inactivate the live vaccine,” warns Daniel Floret, a paediatric expert and the president of the technical committee for vaccinations of the French High council of public health, HCSP, an expert group that reports to the French government on new vaccines. 

Besides, some adverse effects could still arise. “[We] should be cautious about possible cases of severe bronchiolitis triggered in some very young children by an inflammatory reaction in the respiratory tract, which has already happened with a RVS vaccine trial in the USA two decades ago,” he tells youris.com.

Yet, with a seemingly good balance between benefits and risks, nasal vaccination developed for other indications, such as influenza, is gaining momentum in some territories. A nasal vaccine against flu has been available in the USA for several years, but it had up until now rarely been implemented in Europe. However, this year, the UK government is offering mass nasal flu vaccination to school children to generate so-called herd immunity. By preventing children from catching flu, their families will be protected. As a result, the disease will not spread. “There are high hopes that important herd immunity effects will be seen with this flu nasal vaccine,” says Adam Finn, a professor of paediatrics at the University of Bristol, UK. 

“As with other vaccines such as the new whooping cough vaccine developed by the project, this herd immunity is only likely to become clear after the vaccine has been widely used for several years,” Finn tells youris.com.

The next step for the project scientists is to team up with pharmaceutical manufacturers for the production of an improved pertussis vaccine for further clinical trials. This process ultimately aims to produce a suitable vaccine for the infant population. But Child Innovac researchers are also pursuing a longer term objective: building a vaccine with genetically engineered pertussis bacteria that include genes of the bronchiolitis virus. This “recombinant “ vaccine would protect children against these two diseases through a single inhalation. 

Image credits to: Lou Bueno

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