The door opens to a safer and more effective vaccination against whooping cough

Whooping cough is a highly contagious infectious respiratory disease caused by the bacteria Bordetella pertussis, which affects people of any age, but is mainly dangerous in babies, as it can cause death. In 2018 alone there were 151.000 cases worldwide; In Spain, since 2015 the number of cases has ranged between 8.300 and 4.000 per year.

Despite the existence of an acellular vaccine against this disease, the incidence has continued to grow in industrialized countries in the last two decades. However, Jesús Arenas, researcher and professor at the University of Zaragoza and member of the IUI Mixto Agroalimentario de Aragón (IA2, UZ-CITA), has just discovered how to eliminate through genetic engineering the toxicity of another vaccine (cellular vaccine) that is more effective but had been discontinued due to generating “adverse effects”. This will allow this new vaccine to replace the current one whose effectiveness has decreased considerably.

The discovery has been patented internationally and has just been published in an article in the scientific journal Vaccines, of which Jesús Arenas is the main author. His methodology could be useful to generate vaccines against other human and animal pathogens that are more economical, effective and safe. The research has been carried out in collaboration with researchers from the University of Utrecht, the Dutch Translational Vaccine Institute (IntraVac) and the University of Vienna.

Two types of vaccines and a resurgent disease
In the 50s, a vaccine based on whole cells was developed, called a cellular vaccine, which turned out to be very effective, drastically reducing the number of cases. In fact, before its introduction, whooping cough was one of the most common diseases in the world, mainly affecting babies and children - 50% developed the disease. However, its administration generated certain toxic effects that are not allowed by the regulations of industrialized countries, so the cellular vaccine was replaced by an acellular vaccine based on antigens, which has been shown to be safe and effective.

Despite the use of this vaccine, in the last two decades the disease has reemerged particularly in industrialized countries where the acellular vaccine is used, with a progressive increase in incidence, hospitalizations and mortality. This scenario is possibly due to the bacteria having evolved and adapted to the immune response induced by the vaccine.

Searching for an alternative for 15 years
Thus, there is currently a demand to create a more effective vaccine. One possibility is the generation of a new cellular vaccine that lacks toxicity. Toxicity is mainly determined by lipopolysaccharide (endotoxin), a structure essential for the survival of the bacteria.

For more than 15 years, various research groups have tried to modify the lipopolysaccharide without success: unlike other species, research has shown that pertussis does not easily accept modifications in this structure. Until now, Jesús Arenas' research group has achieved it.

The great current achievement thanks to genetic engineering
For this discovery, Jesús Arenas' team has used genetic engineering techniques. "We have replaced some enzymes in the lipopolysaccharide synthesis pathway of other bacteria and we have mutated the genes that encode these enzymes in pertussis," comments the researcher. “Many mutations were made but none were effective or the bacteria did not survive.”

However, using very subtle changes, the researchers have managed to generate two mutant strains that are free of endotoxicity. Toxicity tests have been carried out on human cell lines and experimental animals and in one of them the lipopolysaccharide turned out to be nontoxic in all experiments. Studies are now being carried out in the United States to evaluate whether the vaccine is as effective as the previous one and the first results have been very promising.