Waning Immunity to Pertussis Following 5 Doses of DTaP

522

531

Pertussis is a highly contagious respiratory illness caused by the bacterial pathogen Bordetella pertussis. Pertussis rates in the United States have been rising and reached a 50-y high of 42,000 cases in 2012. Although pertussis resurgence is not completely understood, we hypothesize that current acellular pertussis (aP) vaccines fail to prevent colonization and transmission. To test our hypothesis, infant baboons were vaccinated at 2, 4, and 6 mo of age with aP or whole-cell pertussis (wP) vaccines and challenged with B. pertussis at 7 mo. Infection was followed by quantifying colonization in nasopharyngeal washes and monitoring leukocytosis and symptoms. 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. Although all vaccinated and previously infected animals had robust serum antibody responses, we found key differences in T-cell immunity. Previously infected animals and wP-vaccinated animals possess strong B. pertussis-specific T helper 17 (Th17) memory and Th1 memory, whereas aP vaccination induced a Th1/Th2 response instead. The observation that aP, which induces an immune response mismatched to that induced by natural infection, fails to prevent colonization or transmission provides a plausible explanation for the resurgence of pertussis and suggests that optimal control of pertussis will require the development of improved vaccines.whooping cough | T-cell memory | animal models | adaptive immunity |

Section: Discussionmentioning

confidence: 99%

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

Warfel

Zimmerman

Merkel

2013

522

531

“…Based on the 1997 recommendations, the DTaP vaccine series was to be administered in five separate doses at the following ages: 2 months, 4 months, 6 months, between 15 and 18 months of age, and between 4 and 6 years old (40,41). Therefore, it is reasonable to assume that any child born in 1998 or later in the United States that was immunized for pertussis would have received the acellular vaccine (11,12).…”

Section: Discussionmentioning

confidence: 99%

“…The age group 5 years and younger was selected because children age 5 years and younger had the highest incidence rate of pertussis in 2012 (8). The age group 10 to 14 years was selected because it was assumed that children born between 1998 and 2000 only received the acellular vaccine (11,12). Analysis of the 10 to 14 years age group helps to understand the impact of waning immunity on the 2012 pertussis outbreak (9)(10)(11)(12).…”

Section: Methodsmentioning

confidence: 99%

“…Several studies have suggested reasons for the resurgence of pertussis in the United States, including waning immunity from the acellular pertussis vaccine that replaced whole cell vaccine (9)(10)(11)(12)(13)(14)(15)(16)(17)(18); medical advancements that have allowed more effective diagnosis and reporting of pertussis cases (19,20); asymptomatic transmission of B. pertussis from individuals vaccinated with the acellular pertussis vaccine (21,22); evolving variant strains of B. pertussis circulating that are less protected by the vaccine (23)(24)(25); and a decrease in vaccine coverage that has compromised herd/community immunity (1,(26)(27)(28)(29)(30)(31)(32)(33)(34)(35). It is clear that the rise in reported pertussis cases in the United States is a multifaceted problem not fully captured in national or state-level data.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Geospatial analysis of nonmedical vaccine exemptions and pertussis outbreaks in the United States

Aloe

Kulldorff

Bloom

2017

Because of increased numbers of recorded pertussis cases in the United States, this study sought to understand the role of nonmedical vaccine exemptions and waning immunity may have had on the resurgence of pertussis in the United States at the community level. We used geospatial scan statistics, SaTScan, version 9.4, to analyze nonmedical vaccine exemptions of children entering kindergarten in 2011 and 2012 and reported pertussis cases in 2012 for children in age groups 5 years and younger and 10 to 14 years. Eight statistically significant clusters of nonmedical vaccine exemptions in kindergarteners and 11 statistically significant clusters of pertussis cases in children and adolescents were identified and geospatially linked. Forty-five percent of the counties in the study had high rates of nonmedical vaccine exemptions. The proportion of kindergarteners with nonmedical vaccine exemptions was 2.8 times larger in the identified exemption clusters. In addition, 31 counties had geographic clusters of high rates of pertussis in children ages 10 to 14 years old, consistent with waning immunity. Our findings are consistent with the view that geographic clusters of nonmedical vaccine exemptions and waning immunity may have been factors contributing to community-level pertussis outbreaks.

“…A variety of explanations for pertussis resurgence have been proposed, ranging from improvements in surveillance and diagnostics (7) to reduced protection afforded by vaccination, whether due to the waning of vaccine-derived immunity (8), the evolution of the etiological agent (the bacterium Bordetella pertussis) (9), the switch from whole-cell to acellular vaccines (10), or the invasion and spread of Bordetella congeners (11). It has also been demonstrated that even in the absence of changes in the nature of transmission, vaccine, or reporting, pertussis resurgence might be expected in some countries as an inevitable consequence of insufficient historical vaccination (12).…”

mentioning

confidence: 99%

Combating pertussis resurgence: One booster vaccination schedule does not fit all

Riolo

Rohani

2015

Pertussis has reemerged as a major public health concern in many countries where it was once considered well controlled. Although the mechanisms responsible for continued pertussis circulation and resurgence remain elusive and contentious, many countries have nevertheless recommended booster vaccinations, the timing and number of which vary widely. Here, using a stochastic, age-stratified transmission model, we searched for cost-effective booster vaccination strategies using a genetic algorithm. We did so assuming four hypothesized mechanisms underpinning contemporary pertussis epidemiology: (I) insufficient coverage, (II) frequent primary vaccine failure, (III) waning of vaccine-derived protection, and (IV) vaccine "leakiness." For scenarios I-IV, successful booster strategies were identified and varied considerably by mechanism. Especially notable is the inability of booster schedules to alleviate resurgence when vaccines are leaky. Critically, our findings argue that the ultimate effectiveness of vaccine booster schedules will likely depend on correctly pinpointing the causes of resurgence, with misdiagnosis of the problem epidemiologically ineffective and economically costly.R econciling the historical successes of routine infant pertussis vaccination programs in reducing incidence (1-3) with the recent resurgence in a number of highly vaccinated countries (4, 5) has proved challenging, especially in the context of the global heterogeneity in contemporary pertussis epidemiology (6). A variety of explanations for pertussis resurgence have been proposed, ranging from improvements in surveillance and diagnostics (7) to reduced protection afforded by vaccination, whether due to the waning of vaccine-derived immunity (8), the evolution of the etiological agent (the bacterium Bordetella pertussis) (9), the switch from whole-cell to acellular vaccines (10), or the invasion and spread of Bordetella congeners (11). It has also been demonstrated that even in the absence of changes in the nature of transmission, vaccine, or reporting, pertussis resurgence might be expected in some countries as an inevitable consequence of insufficient historical vaccination (12).Disentangling the many pathways to pertussis resurgence is particularly difficult because pertussis immunity and, in particular, vaccine-derived immunity are not well understood (13). With no known reliable serological marker of protection (14), the properties of infection-and vaccine-derived immunity against pertussis must be inferred indirectly (15). However, the models of pertussis immunity that best reconcile individual-level clinical data (16) and population-level incidence data (17), respectively, are strikingly different. Data from serological studies (16, 18) and animal models (19) paint a picture of a vaccine that protects against disease for a limited duration and may afford little protection against transmission. In contrast, large-scale pertussis incidence data from countries such as Denmark (20), England and Wales (21), Thailand (17), and Sweden (2...