Waning Protection after Fifth Dose of Acellular Pertussis Vaccine in Children

Kaiser Permanente Vaccine Study Center, Oakland, CA 94612, USA.
New England Journal of Medicine (Impact Factor: 55.87). 09/2012; 367(11):1012-9. DOI: 10.1056/NEJMoa1200850
Source: PubMed


In the United States, children receive five doses of diphtheria, tetanus, and acellular pertussis (DTaP) vaccine before 7 years of age. The duration of protection after five doses of DTaP is unknown.
We assessed the risk of pertussis in children in California relative to the time since the fifth dose of DTaP from 2006 to 2011. This period included a large outbreak in 2010. We conducted a case-control study involving members of Kaiser Permanente Northern California who were vaccinated with DTaP at 47 to 84 months of age. We compared children with pertussis confirmed by a positive polymerase-chain-reaction (PCR) assay with two sets of controls: those who were PCR-negative for pertussis and closely matched controls from the general population of health-plan members. We used logistic regression to examine the risk of pertussis in relation to the duration of time since the fifth DTaP dose. Children who received whole-cell pertussis vaccine during infancy or who received any pertussis-containing vaccine after their fifth dose of DTaP were excluded.
We compared 277 children, 4 to 12 years of age, who were PCR-positive for pertussis with 3318 PCR-negative controls and 6086 matched controls. PCR-positive children were more likely to have received the fifth DTaP dose earlier than PCR-negative controls (P<0.001) or matched controls (P=0.005). Comparison with PCR-negative controls yielded an odds ratio of 1.42 (95% confidence interval, 1.21 to 1.66), indicating that after the fifth dose of DTaP, the odds of acquiring pertussis increased by an average of 42% per year.
Protection against pertussis waned during the 5 years after the fifth dose of DTaP. (Funded by Kaiser Permanente).

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    • "Although diagnostic and reporting factors have played a part, a recent review by the Strategic Advisory Group of Experts of the World Health Organization concluded that Australia, the US and the UK had experienced a true resurgence [5]. Waning of acellular vaccine effectiveness has been documented following three doses in pre-school children in Australia [6] and five doses in school-aged children in the US [7], but many factors associated with resurgence are not understood [5]. Mathematical models provide a principled framework to study drivers of resurgence and consider options for reconfiguring immunisation schedules to regain pertussis control. "
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    ABSTRACT: Pertussis resurgence has been reported from several developed countries with long-standing immunisation programs. Among these, Australia in 2003 discontinued an 18 months (fourth) booster dose in favour of an adolescent (fifth) dose. We developed a model to evaluate determinants of resurgence in Australia and alternative vaccine strategies for mitigation. Novel characteristics of our model included the use of seroepidemiologic data for calibration, and broad investigation of variables relevant to transmission of, and protection against, pertussis. We simulated multiple parameter combinations, retaining those consistent with observed data for subsequent use in predictive models comparing alternative vaccination schedules. Reproducing the early control of pertussis followed by late resurgence observed in Australia required natural immunity to last decades longer than vaccine-acquired immunity, with mean duration exceeding 50 years in almost 90% of simulations. Replacement of the dose at 18 months with an adolescent dose in 2003 resulted in a 40% increase in infections in the age group 18-47 months by 2013. A six dose strategy (2, 4, 6, 18 months, 4 and 15 years) yielded a reduction in infection incidence (pre-school 43%, infants 8%) greater than any alternative strategies considered for timing of five administered doses. Our finding that natural immunity drives long-term trends in pertussis cycles is relevant to a range of pertussis strategies and provides the necessary context in which to consider maternal vaccination. Comparatively short-lived vaccine-acquired immunity requires multiple boosters over the first two decades of life to maximise reduction in infections.
    Vaccine 09/2015; DOI:10.1016/j.vaccine.2015.09.025 · 3.62 Impact Factor
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    • "Therefore, it is 60 possible that the immune responses induced by 3-5 antigens from the single isolate used to 61 manufacture the aP vaccine do not protect against at least some of the current circulating 62 strains. Secondly, the waning protective immunity observed following immunization with aP 63 vaccines suggests that these vaccines fail to generate effective immunological memory (Klein 64 et al., 2012), (Sheridan et al., 2012, Klein et al., 2013, Liko et al., 2013, Witt et al., 2013). "
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    ABSTRACT: Current acellular pertussis vaccines have various shortcomings, which may contribute to their sub-optimal efficacy and waning immunity in vaccinated populations. This calls for the development of new pertussis vaccines capable of inducing long-lived protective immunity. Immunization with whole cell pertussis vaccines and natural infection with Bordetella pertussis induce distinct and more protective immune responses when compared with immunization with acellular pertussis vaccines. Therefore, the immune responses induced with whole cell vaccine or after infection can be used as a benchmark for the development of third generation vaccines against pertussis. Here, we review the literature on the immunology of B. pertussis infection and vaccination and discuss the lessons learned that will help in the design of improved pertussis vaccines.
    Pathogens and Disease 09/2015; DOI:10.1093/femspd/ftv067 · 2.40 Impact Factor
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    • "These include genetic changes in circulating B. pertussis, increased recognition and reporting of pertussis by the application of new, more sensitive, laboratory diagnostic tests (Cherry 2012a). Recent epidemiological studies suggest that the resurgence of pertussis is due to a more rapid waning of aP vaccine than of wP vaccine-induced immunity (Klein et al. 2012; Koepke et al. 2014). A key aspect to take into account when studying immunity in human populations is the estimation of the length of protection that follows from healing infection or vaccination. "
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    ABSTRACT: The recent immunological investigations, stemming from the studies performed in the nineties within the clinical trials of the acellular pertussis (aP) vaccines, have highlighted the important role played by T-cell immunity to pertussis in humans. These studies largely confirmed earlier investigations in the murine respiratory infection models that humoral immunity alone is not sufficient to confer protection against Bordetella pertussis infection and that T-cell immunity is required. Over the last years, knowledge of T-cell immune response to B. pertussis has expanded broadly, taking advantage of the general progress in the understanding of anti-bacterial immunity and of refinements in methods to approach immunological investigations. In particular, experimental models of B. pertussis infection highlighted the cooperative role played by T-helper (Th)1 and Th17 cells for protection. Furthermore, the new baboon experimental model suggested a plausible explanation for the differences observed in the strength and persistence of protective immunity induced by the acellular or whole-cell pertussis vaccines and natural infection in humans, contributing to explain the upsurge of recent pertussis outbreaks. Despite the progress, open questions remain, the answer to them will possibly provide better tools to fight one of the hardest-to-control vaccine preventable disease. © FEMS 2015. All rights reserved. For permissions, please e-mail:
    Pathogens and Disease 08/2015; 73(7). DOI:10.1093/femspd/ftv051 · 2.40 Impact Factor
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