Whooping Cough, Vaccine and Shedding

Warfel, Zimmerman, Merkel

Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model

Proceedings of the National Academy of Sciences (PNAS), 111 (2) 787-792,

First published: November 25, 2013

DOI: https://doi.org/10.1073/pnas.1314688110

Vaccine shedding, or viral shedding, happens when a vaccine releases parts of a virus, which can occasionally occur following a viral infection caused by an attenuated (or "live virus") vaccine, resulting in the spread of an infection.

Currently, NHS offers acellular pertussis (whooping cough) vaccines for babies (Infanrix Hexa, Vaxelis) and in pregnancy (Adacel).

The main differences between acellular pertussis (aP) and whole-cell pertussis (wP) vaccines are:

• Immunogenicity: wP vaccines are more immunogenic than aP vaccines. 

• Reactogenicity: wP vaccines are more likely to cause adverse events than aP vaccines. 

• Duration of immunity: wP vaccines provide longer-lasting immunity than aP vaccines. 

• Cost: wP vaccines are cheaper to produce than aP vaccines. 

• Safety: aP vaccines are considered safe for all age groups, while wP vaccines are less useful for adolescents and adults due to their increased risk of adverse events. 

• Composition: wP vaccines contain the entire inactivated organism, while aP vaccines contain parts of the organism, such as the pertussis toxin. 

• Use : in low and middle-income countries, wP vaccines are the preferred choice. In high-income countries, most people receive the diphtheria, tetanus, acellular pertussis (DTaP) vaccine. 

Over the last 30 years pertussis has resurged in the United States. It began during wP vaccine era but since the introduction of aP vaccines it has picked up pace. This has made many researchers hypothesise that aP vaccines are less effective than the wP they replaced.

In this study researchers showed that nonhuman primates vaccinated with aP were protected from severe symptoms but not infection and readily transmitted Bordetella pertussis (whooping cough) to contacts. To test their hypothesis, infant baboons were vaccinated at 2, 4, and 6 months of age with aP or wP vaccines and challenged with B. pertussis at 7 months. Infection was followed by quantifying colonisation in nasopharyngeal washes (procedure for collecting cells from back of the nose) and monitoring white blood cell count and symptoms. Researchers found:

"Baboons vaccinated with aP were protected from severe pertussis-associated symptoms but not from colonization, did not clear the infection faster than naïve animals, and readily transmitted B. pertussis to unvaccinated contacts. Vaccination with wP induced a more rapid clearance compared with naïve and aP-vaccinated animals. By comparison, previously infected animals were not colonized upon secondary infection."

Researchers mention several other observational studies which have concluded that children primed with aP vaccine had a twofold to fivefold greater risk of pertussis diagnosis compared with wP-primed children. However, neither vaccine was able to prevent colonisation as well as immunity from a previous infection.

They discussed other observational studies which suggest that asymptomatic pertussis can occur in vaccinated children and adults based on PCR or serological data. However, during the aP vaccine trials, participants were screened for B. pertussis infection only if they presented with pertussis-like symptoms and at least 7–21 day cough. Researchers concluded:

Therfore, no experimental data exist on whether aP vaccination prevents B. pertussis colonization or transmission in humans.

Reasons given for whooping cough resurgence

• "Hampering our ability to counteract this resurgence is the fact that pertussis pathogenesis and immunity to natural infection have not been well studied in humans because typical pertussis is sporadic given high rates of vaccination in developed countries. Human challenge studies have been proposed but never conducted due to a variety of logistical and ethical problems including the potential for severe disease, the lack of an effective therapeutic for established disease, and the highly contagious nature of pertussis. Although a variety of small-animal models have been used to study pertussis, none of them adequately reproduce the human disease."

  
  

• "Animals vaccinated with wP, which cleared infection faster than naïve and aP-vaccinated animals, showed similar but weaker T-cell responses. (..) Future studies will compare the immune response induced by wP vaccines produced by three different manufacturers. In comparison with natural infection and wP, aP-induced immunity was mismatched, showing a Th2 response with a weaker Th1 response and no significant Th17 response."

• "We hypothesized an additional explanation for pertussis resurgence is that aP-vaccinated individuals can act as asymptomatic or mildly symptomatic carriers and contribute significantly to transmission in the population. Observational studies suggest that asymptomatic pertussis can occur in vaccinated children and adults based on PCR or serological data."