Genetically detoxified pertussis toxin (PT-9K/129G): implications for immunization and vaccines

Seubert, Anja; D’Oro, Ugo; Scarselli, María; Pizza, Mariagrazia

doi:10.1586/14760584.2014.942641

Cited by 37 publications

(36 citation statements)

References 88 publications

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“…It is thus urgent to define whether improved booster vaccines might be developed for future aP-primed pregnant women. Existing options include the use of genetically detoxified PT, shown to be more immunogenic than chemically detoxified PT, inducing higher neutralizing antibody titers and a Th1/ Th17 response that may improve mucosal responses (Seubert et al 2014). To reduce immune escape, additional antigens such as improved fimbriae antigens (Gorringe and Vaughan 2014), adenylate cyclase toxin (ACT), or the autotransporter BrkA could be considered (Brummelman et al 2015).…”

Section: What Lies Ahead?mentioning

confidence: 99%

What Is Wrong with Pertussis Vaccine Immunity?

Eberhardt

Siegrist

2017

Cold Spring Harb Perspect Biol

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The high incidence of pertussis in vaccinated adolescents suggests the failing of immune memory. We argue that acellular pertussis vaccines generate memory cells that are effectively reactivated by boosters better than by exposure. We propose that there are two main causes. One is the induction of vaccine-specific immunity rather than pathogen-specific immunity. The second is that strictly mucosal infections such as poorly reactivate memory B and T cells residing deep in lymph nodes or tissues. Developing new vaccines for infants or adolescents will be immunologically and economically challenging. Let us hope that maternal and infant immunization, to date the most effective strategies against pertussis death, will remain so.

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Section: What Lies Ahead?mentioning

confidence: 99%

What Is Wrong with Pertussis Vaccine Immunity?

Eberhardt

Siegrist

2017

Cold Spring Harb Perspect Biol

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“…Both goals will require reformulation of pertussis vaccine constituents, both antigens and adjuvants. The most obvious strategies are to use genetically rather than chemically inactivated PT (Seubert et al 2014); to use adjuvants that better stimulate innate immunity and memory; and/or to add new B. pertussis virulence factors to the vac- Figure 2. New aP vaccine should be aimed to increase priming and boostability of current subunit vaccine through the addition of adjuvants that will program a more Th1/Th17 immune profile and possibly the addition of more subunit Ags inducing bactericidal activity to limit or prevent colonization.…”

Section: Resultsmentioning

confidence: 99%

What Is Wrong with Pertussis Vaccine Immunity?

Burdin

Handy

Plotkin³

2017

Cold Spring Harb Perspect Biol

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Pertussis is resurgent in some countries, particularly those in which children receive acellular pertussis (aP) vaccines in early infancy and boosters later in life. Immunologic studies show that, whereas whole-cell pertussis (wP) vaccines orient the immune system toward Th1/Th17 responses, acellular pertussis vaccines orient toward Th1/Th2 responses. Although aP vaccines do provide protection during the first years of life, the change in T-cell priming results in waning effectiveness of aP as early as 2-3 years post-boosters. Although other factors, such as increased virulence of pertussis strains, better diagnosis, and better surveillance may play a role, the increase in pertussis appears to be the result of waning immunity. In addition, studies in baboon models, requiring confirmation in humans, show that aP is less able to prevent nasopharyngeal colonization of Bordetella pertussis than wP or natural infection. GREAT DEBATES What are the most interesting topics likely to come up over dinner or drinks with your colleagues? Or, more importantly, what are the topics that don't come up because they are a little too controversial? In Immune Memory and Vaccines: Great Debates, Editors Rafi Ahmed and Shane Crotty have put together a collection of articles on such questions, written by thought leaders in these fields, with the freedom to talk about the issues as they see fit. This short, innovative format aims to bring a fresh perspective by encouraging authors to be opinionated, focus on what is most interesting and current, and avoid restating introductory material covered in many other reviews. The Editors posed 13 interesting questions critical for our understanding of vaccines and immune memory to a broad group of experts in the field. In each case, several different perspectives are provided. Note that while each author knew that there were additional scientists addressing the same question, they did not know who these authors were, which ensured the independence of the opinions and perspectives expressed in each article. Our hope is that readers enjoy these articles and that they trigger many more conversations on these important topics.

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“…Indeed, the use of rPT improves protective efficacy against wild-type strains [6]. A recent clinical study indicated that boosting with rPT was safe and induced significantly higher neutralizing antibodies than current acellular pertussis vaccines (BioNet forthcoming data, http://www.businesswire.com/ news/home/20141015006848/en/BioNet-Update-RecombinantAcellular-Pertussis-Vaccine-BioJapan#.VGK69skVji0).…”

Section: Discussionmentioning

confidence: 99%

“…Novel strategies would thus be welcome. The use of poorly immunogenic chemically-detoxified pertussis toxin (PT) likely contributes to limit pertussis immunity [5]: it removes up to 80% of surface epitopes, reducing neutralizing antibodies, and directing B cells toward vaccine-specific rather than pathogen-specific epitopes [6]. PT with wild-type immunogenicity profile but deprived of toxicity is best achieved through genetic rather than chemical detoxification [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Needle-free and adjuvant-free epicutaneous boosting of pertussis immunity: Preclinical proof of concept

Gavillet

Mondoulet

Dhelft

et al. 2015

Vaccine

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The limited durability of pertussis vaccine-induced protection requires novel approaches to reactivate immunity and limit pertussis resurgence in older children and adults. We propose that periodic boosters could be delivered using a novel epicutaneous delivery system (Viaskin) to deliver optimized pertussis antigens such as genetically-detoxified pertussis toxin (rPT). To best mimic the human situation in which vaccine-induced memory cells persist, whereas antibodies wane, we developed a novel adoptive transfer murine model of pertussis immunity. This allowed demonstrating that a single application of Viaskin delivering rPT and/or pertactin and filamentous hemagglutinin effectively reactivates vaccine-induced pertussis immunity and protects against Bordetella pertussis challenge. Recalling pertussis immunity without needles nor adjuvant may considerably facilitate the acceptance and application of periodic boosters.

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Genetically detoxified pertussis toxin (PT-9K/129G): implications for immunization and vaccines

Cited by 37 publications

References 88 publications

What Is Wrong with Pertussis Vaccine Immunity?

What Is Wrong with Pertussis Vaccine Immunity?

What Is Wrong with Pertussis Vaccine Immunity?

Needle-free and adjuvant-free epicutaneous boosting of pertussis immunity: Preclinical proof of concept

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