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Abstract
The recent epidemics of pertussis (whooping cough) in parts of the USA and Australia have led to the largest numbers of annual cases reported in over half a century. These epidemics demonstrated a new pattern, with particularly high rates of disease among pre-adolescents and early adolescents. These high rates of pertussis coincided with the first cohorts vaccinated with purely acellular pertussis vaccine, which replaced whole-cell pertussis (wP) vaccine in the later 1990s in the USA and Australia. Studies undertaken during these epidemics provide new evidence of more rapid waning of acellular pertussis-containing vaccines and longer-term protection from effective wP-containing vaccines. There is evidence that receiving wP as at least the first dose of pertussis-containing vaccine provides greater and more long-lived protection, irrespective of the nature of subsequent doses. This evidence will be reviewed together with the immunobiology associated with both vaccines, and the implications for pertussis control discussed.
Financial & competing interests disclosure
SB Lambert has membership of Advisory Boards to GSK (pneumococcal vaccine) and Sanofi Pasteur (influenza vaccine). K Grimwood has previously been a member of an Advisory Board to GSK on pneumococcal conjugate vaccines. T Snelling was an investigator on a study of rotavirus vaccination, which was funded in part by GSK Australia. P McIntyre is chief investigator on a vaccine trial funded by the National Health and Medical Research Council (NHMRC) which received in kind support from GSK and an investigator on another vaccine trial which received in kind support from Pfizer vaccines. K Grimwood receives research funding from the Australian NHMRC. SB Lambert is supported by an NHMRC early career fellowship and a Children’s Health Foundation (CHF) People Support Fellowship. S Sheridan is supported by an NHMRC postgraduate scholarship and a CHF clinical PhD scholarship. T Snelling is supported by an NHMRC Early Career Fellowship and a Fiona Stanley Investigatorship. P McIntyre’s Center receives funding from the Australian and New South Wales governments. The funding bodies had no role in the conduct of the review or writing the manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Key issues
While variability has been demonstrated among both whole-cell pertussis (wP) and acellular pertussis (aP) vaccines, highly efficacious wP vaccines provide longer-term protection than aP vaccines.
In the USA and Australia, priming with wP appears to be more effective than priming with aP, both prior to and following aP booster vaccinations. The aP boosters do not neutralize the advantage provided by wP priming.
The differential effectiveness of not only priming in early childhood, but of aP boosters later in life by the type of vaccine used for priming has implications for future patterns of age-specific pertussis incidence and the appropriate timing of booster vaccinations to provide protection.
Limited evidence suggests the nature of the first pertussis vaccine received may be particularly important in determining long-term protection, with a highly effective wP as an initial vaccine providing superior protection than a course commencing with aP. However, further investigation of this hypothesis is required to draw definitive conclusions.
The immunobiology underlying the differential effectiveness between aP and wP vaccines is incompletely understood. However, wP, more similar to natural infection stimulates a mixed Th1/Th2 response, whereas aP priming stimulates a predominantly Th2 response.
The hypothesized importance of the initial dose of vaccine on long-term protection may be related to linked epitope suppression, where the initial exposure locks in the immune response to certain epitopes and inhibits response to other linked epitopes on subsequent exposures.
Ecological and other observational study evidence on the differential effectiveness of wP- and aP-primed children indicate the replacement of wP by aP in the US and Australian contexts contributed to recent pertussis epidemiology, particularly the high incidence of disease of fully aP-primed pre-adolescents and adolescents.
While aP vaccines wane more rapidly than wP vaccines, both aP and wP provide a high level of protection against disease shortly after priming, thereby providing very good protection to vaccinated infants.
Evidence from a baboon model found aP vaccine did not prevent asymptomatic infection in aP-vaccinated baboons or transmission from aP-vaccinated baboons to unvaccinated baboons. In contrast, wP-vaccinated baboons cleared infection more rapidly.
New pertussis vaccines or new formulations of current vaccines are unlikely to be available within the next 10 years.
Maintaining high vaccination coverage and appropriately timed and targeted boosters remains central to pertussis control.