Should We Bring Back the Whole-Cell Pertussis Vaccine?

Paul A. Offit, MD


April 29, 2016

Editorial Collaboration

Medscape &

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Hi. My name is Paul Offit. I'm talking to you from the Vaccine Education Center at the Children's Hospital of Philadelphia, about a paper that was just published in JAMA Pediatrics[1] titled "Epidemiological and Economic Effects of Priming with the Whole-Cell Bordetella pertussis Vaccine."

Let me put this paper in context. Prior to the pertussis vaccines being introduced in the United States in the 1940s, there were about 8000 deaths from whooping cough every year, primarily in children. With the introduction of that vaccine, there was a dramatic decrease in the incidence of both disease and death. The vaccine was made using the whole bacteria, meaning that the bacteria were grown in media, and then both bacteria and toxins produced by the bacteria were killed with an inactivating agent such as formaldehyde.

Although the whole-cell pertussis vaccine worked very well, it had a difficult safety profile. It could cause fever (even high fever), high-pitched inconsolable crying, seizures (with or without fever), and hypotonic-hyporesponsive syndrome. As a consequence, there was a push to move to the so-called "acellular" pertussis vaccine—meaning that it wasn't made from the whole bacteria. Depending on the product, the acellular vaccine was made using two to five specific proteins from that pertussis bacteria.

It was a much safer, but also a less effective, vaccine. Since the acellular pertussis vaccine was introduced in the mid-1990s, we have seen an increase in cases of whooping cough, in part because of the less effective acellular vaccine.

As we transitioned from the whole-cell bacterial vaccine to the purified protein vaccine, some children received only the whole-cell vaccine, some received only the acellular vaccine, and some received a combination—meaning they were primed with the whole-cell vaccine but then boosted with the acellular vaccine. This study looked at what happened to the latter group of children.

They found that priming with the whole-cell vaccine and then finishing the series with the acellular vaccine produced a much better immune response. Using mathematical modeling, this group determined that using a single dose of the whole-cell vaccine to prime, and then acellular vaccine for booster doses, would result in a 95% reduction in the incidences of disease, as well as a 96% reduction in the incidence of disease in neonates.

This is just a theoretical mathematical modeling paper. They did not actually conduct this experiment. Frankly, it would be tough to move back to the whole-cell vaccine because of the perception that it caused permanent harm in terms of epilepsy or developmental delays, although that wasn't true. We would struggle against that perception of harm. It is an interesting thought, and certainly, if we were to do it, we would be better off than we are today. Thank you.