"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). "
[Show abstract][Hide abstract] 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
"In the last years there has been a resurgence of pertussis cases and infant deaths in countries with high vaccination coverage   , emphasizing the need for a different vaccine approach to provide protection for the most susceptible infants. Studies have shown that a primary dose of a Pw-vaccine reduces the risk of pertussis compared to a primary dose of a Pa-vaccine [30–32], and the live attenuated BPZE1 vaccine may be a promising priming candidate in that context. "
[Show abstract][Hide abstract] ABSTRACT: Despite high vaccination coverage, pertussis is still a global concern in infant morbidity and mortality, and improved pertussis vaccines are needed. A live attenuated Bordetella pertussis strain, named BPZE1, was designed as an intranasal vaccine candidate and has recently been tested in man in a phase I clinical trial. Here, we report the evaluation of the B-cell responses after vaccination with BPZE1. Forty-eight healthy males with no previous pertussis-vaccination were randomized into one of three dose-escalating groups or into a placebo group. Plasma blast- and memory B-cell responses were evaluated by ELISpot against three different pertussis antigens: pertussis toxin, filamentous haemagglutinin and pertactin. Seven out of the 36 subjects who had received the vaccine were colonized by BPZE1, and significant increases in the memory B-cell response were detected against all three tested antigens in the culture-positive subjects between days 0 and 28 post-vaccination. The culture-positive subjects also mounted a significant increase in the filamentous haemagglutinin-specific plasma blast response between days 7 and 14 post-vaccination. No response could be detected in the culture-negatives or in the placebo group post-vaccination. These data show that BPZE1 is immunogenic in humans and is therefore a promising candidate for a novel pertussis vaccine. This trial is registered at ClinicalTrials.gov (NCT01188512).
"Pertussis continues to be the most poorly controlled bacterial vaccine-preventable disease despite high levels of vaccine coverage . Since the 1980s, different pertussis epidemics have arisen with a high burden of disease among teenagers, a group that previously had a low risk of pertussis    . Increased awareness and improved diagnostics coincide with increased notification of pertussis , but do not completely account for it. "
[Show abstract][Hide abstract] ABSTRACT: To better understand vaccine-induced protection and its potential failure in light of recent whooping cough resurgence, we evaluated quantity as well as quality of memory T cell responses in B. pertussis-vaccinated preadolescent children. Using a technique based on flow cytometry to detect proliferation, cytokine production and phenotype of antigen-specific cells, we evaluated residual T cell memory in a cohort of preadolescents who received a whole-cell pertussis (wP; n=11) or an acellular pertussis vaccine (aP; n=13) during infancy, and with a median of 4 years elapsed from the last pertussis booster vaccine, which was aP for all children. We demonstrated that B. pertussis-specific memory T cells are detectable in the majority of preadolescent children several years after vaccination. CD4(+) and CD8(+) T cell proliferation in response to pertussis toxin and/or filamentous hemagglutinin was detected in 79% and 60% of the children respectively, and interferon-γ or tumor necrosis factor-α producing CD4(+) T cells were detected in 65% and 53% of the children respectively. Phenotyping of the responding cells showed that the majority of antigen-specific cells, whether defined by proliferation or cytokine production, were CD45RA(-)CCR7(-) effector memory T cells. Although the time since the last booster vaccine was significantly longer for wP-compared to aP-vaccinated children, their proliferation capacity in response to antigenic stimulation was comparable, and more children had a detectable cytokine response after wP-compared to aP-vaccination. This study supports at the immunological level recent epidemiological studies indicating that infant vaccination with wP induces longer lasting immunity than vaccination with aP-vaccines.
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