Tod J Merkel's research while affiliated with U.S. Food and Drug Administration and other places

... [35][36][37] Asymptomatic BP infections are highly prevalent in human populations, [38][39][40][41][42][43] compatible with widespread sub-clinical reinfection. Adaptive immune responses associated with reinfections have been studied in the baboon and mouse models, 22,23,33,44 but human data are scarce. It would be reasonable to expect that if asymptomatic human reinfections are relatively frequent regardless of previous vaccination status, the breadth of CD4+ T cell responses observed would be directed against aP and non-aP vaccine antigens alike. ...

... Epidemiologically, that suggested that the immunity induced by aP vaccines wanes quicker than those by wP vaccines [5][6][7][8][9] . A number of differences in immune responses between aP and wP vaccines have been identified, such is their T cell polarization [10][11][12][13] , but it is unclear how those differences translate to duration of immunity. By establishing and testing computational models that attempt to predict the cascade of events that follow B. pertussis booster vaccination, we will improve our understanding of the mechanisms underlying these events, with the ultimate goal to identify what variables induce a strong and durable recall response. ...

... 3 Because B pertussis is highly infectious, 4 pertussis vaccines should ideally prevent not only pertussis disease, but also B pertussis colonising infection and transmission. 5 Two types of pertussis vaccines are currently in use: whole-cell vaccines and, more recently, acellular pertussis vaccines (aPVs). 6 Many countries began to exclusively use aPVs in the 1990s or early 2000s, and subsequently pertussis infections increased in frequency. ...

... These new generation vaccines are similar to diphtheria vaccines in that they are not composed of the whole pathogen, but of certain antigens selected for their role in triggering disease. One of these antigens, present in all ACVs, is pertussis toxin, which is thought to be responsible for most of pertussis symptoms (Carbonetti, 2010;Gregg and Merkel, 2019;Scanlon et al., 2019aScanlon et al., , 2019b. Interestingly, at least two countries using ACVs have reported the detection of toxin-deficient strains in recent years (Bouchez et al., 2021;Williams et al., 2016). ...

... For pertussis antigens, no immunological correlates of protection (ICP) exist; however, studies investigating pertussis vaccine ICPs demonstrated that the presence of antibodies against PT, PRN, and fimbriae correlated with protection, but antibodies against FHA did not [25][26][27][28]. The lack of a correlation between anti-FHA antibodies with disease protection after vaccination with aP vaccines does not however rule out the role of other immune mechanisms in response to FHA [29,30]. Further, previous Tdap vaccine studies showed that vaccine administration produced antibody GMC /GMT levels against pertussis antigens that were higher than those observed following primary immunization with pediatric formulations with whom efficacy was shown in a household contact study in Germany and in a primary efficacy study in Italy [18,20,21,31,32]. ...

... One of the crucial factors leading to "pertussis resurgence" is a change in transmission mode. After mass vaccination, adolescents and adults with low levels of protective antibodies became carriers for transmission of pertussis to infants and young children (4). Due to the atypical symptoms of pertussis in adolescents and adults, specific laboratory measurements, such as culture, serological tests, and PCR assays, now play an essential role in diagnosis (5). ...