AUGMENTATION DE L’INCIDENCE DE LA COQUELUCHE DANS LE MONDE ? Diagnostic biologique plus performant Couverture vaccinale insuffisante Adoption des acellulaires dans de nombreux pays – Moins efficace ? – Durée de protection moins longue ? Modification des souches…vaccins moins efficaces 1

Pourquoi vacciner contre la coqueluche ? Eradiquer la maladie : Non Protéger d’une maladie grave chez le petit nourrisson +++ Protéger d’une maladie gênante chez le grand enfant et l’adulte + Assurer une immunité de groupe protégeant contre les grandes épidémies + 2

Pourquoi vacciner les adultes contre la coqueluche ? Eradiquer la maladie Les protéger d’une maladie gênante, exceptionnellement grave Les empêcher de contaminer les petits enfants Assurer une immunité de groupe protégeant contre les grandes épidémies 3

Review of Randomized Trials Conclusions aP vaccines effective in preventing confirmed pertussis Marginally less effective than the best wP vaccines 1,2,3, and 5 component vaccines all effective Notably, no resurgence in Denmark despite monocomoponent vaccine No simple relationship between immunogenicity and efficacy

ANIMAL MODEL Baboon Study Attribution: Tod J. Merkel et al Laboratory of Respiratory and Special Pathogens CBER/FDA

Animal Model (Baboon Study) wP and aP both protective against disease Attribution: Tod J. Merkel et al Laboratory of Respiratory and Special Pathogens CBER/FDA

Animal Model (Baboon Study) aP did not prevent infection Attribution: Tod J. Merkel et al Laboratory of Respiratory and Special Pathogens CBER/FDA

Animal Model (Baboon Study) aP did not prevent transmission Attribution: Tod J. Merkel et al Laboratory of Respiratory and Special Pathogens CBER/FDA

Animal Model (Baboon Study) Conclusions Infection, wP, aP all protected against symptomatic disease wP provided some sterilizing immunity Less than natural infection Induces Th1 and Th17 memory aP did not prevent infection and transmission Higher Th2 but lower Th1 and Th17 responses Lack of mucosal immunity induction likely has role in pertussis resurgence References Warfel JM, Beren J, Kelly VK, Lee G, Merkel TJ. Nonhuman primate model of pertussis. Infect Immun 2012;80(4): Warfel JM, Zimmerman LI, Merkel TJ. Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model. Proc Natl Acad Sci 2014;111(2): Warfel JM, Papin JF, Wolf RF, Zimmerman LI, Merkel TJ. Maternal and neonatal vaccination protects newborn baboons from pertussis infection. J Infect Dis 2014.

Summary Pertussis vaccination very effective in reducing disease wP and aP both effective in reducing infant mortality No evidence of broad resurgence at global level Cyclic recurrent patterns of pertussis still observed aP disease prevention Lower initial efficacy and faster waning of immunity Reduced impact on infection and transmission Modelling and baboon data support hypothesis that wP to aP transition is associated with localized disease resurgence

Si on veut protéger les petits enfants Vaccination précoce semaines (moins) Vaccination des femmes enceintes +++ Cocooning + 11