Changing from whole-cell to acellular pertussis vaccines would trade superior tolerability for inferior protection

Abstract

Notifications of infant deaths, assumed to be related to the introduction of new pentavalent DTwP-Hib-HBV childhood vaccines, caused, during 2008–2010 in few Asian countries, temporary interruptions of the respective vaccination programs. The sudden appearance of fatal cases was due to increased awareness/publicity and improved safety monitoring/reporting in countries with relatively high background infant mortalities. WHO investigations could not establish any causal relationships and vaccinations were again resumed. Recently, questions were raised in one concerned country as to why not to change to less reactogenic acellular pertussis (aP)-containing vaccines that are available in private practice and are generally perceived as ‘better’. For resource-poor countries, the financial impacts render such a switch impossible and would also not be supported by external funding. Furthermore, it would be a disservice to the children, as in recent years evidence of inferior long-term efficacy of aP vaccines has accumulated. This report summarizes current knowledge on comparative whole-cell pertussis (wP) and aP vaccine performance, outlines the new July 2014 WHO guidance on the choice of pertussis vaccines and presents recent data on outbreak protection, antibody waning, long-term protection, wP-priming, pathogen adaptation, transmission and herd immunity.

Keywords:

• acellular vaccines
• antibody waning
• immune priming
• long-term protection
• pathogen adaptation
• pertussis
• re-emergence
• transmission
• vaccination strategies
• whole-cell vaccines

Financial & competing interests disclosure

The preparation of this Special Report was partially supported by a GAVI research fund. The author has 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

• Both whole-cell pertussis (wP) and acellular pertussis (aP) vaccines are equally safe with regard to serious adverse events, that is, there are no long-term sequelae.

• Both wP and aP vaccines, as well as natural infection, do not provide long-term protection, however, protection wanes more rapidly following aP vaccination.

• wP vaccinated children and adolescents are during outbreaks better protected than aP vaccinated ones.

• Priming with ≥1 dose of wP vaccines gives better protection than after aP priming only, irrespective of whether the vaccination series was completed or a recent DTaP booster had been administered.

• Both wP and aP vaccines protect against severe/fatal disease in infants, however, unlike wP vaccines, aP vaccines seem in a non-human primate model not to protect well against colonization and shedding of the pathogen.

• If the failure to interrupt transmission is confirmed in the human setting, this would in view of the high transmissibility of pertussis represent a major setback for aP vaccines as disease control would in the end require 100% vaccination coverage to overcome the lack of herd immunity.

• The exclusive use of aP vaccines seems to be connected with the rise in circulation of pertactin-deficient Bordetella pertussis strains which – according to animal models – might have a selective advantage and would thus help to drive pathogen circulation and epidemics.

• Projects to reverse from aP vaccines to wP vaccines will encounter obstacles due to the low acceptance of higher reactogenic wP vaccines by parents, but should not be dismissed straightaway as an option, at least for priming in infancy.

• WHO advises in view of the lower efficacy of aP vaccines against the change from wP- to aP-containing childhood vaccines; it would mean to trade better tolerability for inferior protection.

• In the setting of rising pertussis incidences, as it is currently being experienced in certain countries using exclusively aP vaccines, only high vaccination coverage of >90% in infants and pre-school children and maternal vaccination to protect neonates and infants too young to be (fully) vaccinated can in the short term control this disease.