Acellular and "low" pertussis vaccines: adverse events and the role of mutations

Higashi, Hisako Gondo; Luna, Expedito; Precioso, Alexander Roberto; Vilela, Marluce S.; Kubrusly, Flávia Saldanha; Dias, Waldely O.; Raw, Isaı́as

doi:10.1590/s0036-46652009000300002

Cited by 12 publications

(4 citation statements)

References 12 publications

(10 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The conventional wP detoxification procedures require a fastidious exposure of the cell suspension to formaldehyde, in order to obtain a decrease in toxicity. According to the methodology described by our group, 13 , 22 a chemical treatment with a mixture of water and butanol, in a short overnight period, partially extracts the LOS from the B. pertussis outer membrane.…”

Section: Discussionmentioning

confidence: 99%

An improved whole cell pertussis vaccine with reduced content of endotoxin

Dias

Ark

Sakauchi

et al. 2013

Human Vaccines & Immunotherapeutics

Self Cite

View full text Add to dashboard Cite

An improved whole cell pertussis vaccine, designated as Plow, which is low in endotoxicity due to a chemical extraction of lipo-oligosaccharide (LOS) from the outer membrane, was evaluated for safety, immunogenicity and potency, comparatively to a traditional whole cell pertussis vaccine. Current whole cell pertussis vaccines are effective but contain large quantities of endotoxin and consequently display local and systemic adverse reactions after administration. Endotoxin is highly inflammatory and contributes considerably to the reactogenicity as well as the potency of these vaccines. In contrast, acellular pertussis vaccines hardly contain endotoxin and are significantly less reactogenic, but their elevated costs limit their global use, especially in developing countries. In this paper, bulk products of Plow and a traditional whole cell vaccine, formulated as plain monocomponents or combined with diphtheria and tetanus toxoids (DTPlow or DTP, respectively) were compared by in vitro and in vivo assays. Chemical extraction of LOS resulted in a significant decrease in endotoxin content (20%) and a striking decline in endotoxin related toxicity (up to 97%), depending on the used in vitro or in vivo test. The LOS extraction did not affect the integrity of the product and, more importantly, did not affect the potency and/or stability of DTPlow. Moreover, hardly any differences in antibody and T-cell responses were observed. The development of Plow is a significant improvement regarding the endotoxicity of whole cell pertussis vaccines and therefore a promising and affordable alternative to currently available whole cell or acellular pertussis vaccines for developing countries.

show abstract

Section: Discussionmentioning

confidence: 99%

An improved whole cell pertussis vaccine with reduced content of endotoxin

Dias

Ark

Sakauchi

et al. 2013

Human Vaccines & Immunotherapeutics

Self Cite

View full text Add to dashboard Cite

show abstract

“…The overall goal of vaccination is the generation of specific, robust, and durable immune responses against the antigen to provide long-term protection against pathogens. Early vaccines that frequently utilized killed whole organisms are reactogenic and are associated with local and systemic adverse reactions, whole cell pertussis vaccines being an example. − Modern vaccines such as acellular pertussis vaccines use highly purified antigens. Such “subunit vaccines” have a much more defined composition, facilitating not only the ease of production and quality control but importantly are also considerably less reactogenic.…”

Section: Introductionmentioning

confidence: 99%

Design and Development of Stable, Water-Soluble, Human Toll-like Receptor 2 Specific Monoacyl Lipopeptides as Candidate Vaccine Adjuvants

et al. 2013

View full text Add to dashboard Cite

Antigens in modern subunit vaccines are largely soluble and poorly immunogenic proteins inducing relatively short-lived immune responses. Appropriate adjuvants initiate early innate immune responses, amplifying subsequent adaptive immune responses. Agonists of TLR2 are devoid of significant pro-inflammatory activity in ex vivo human blood models, and yet potently adjuvantic, suggesting that this chemotype may be a safe and effective adjuvant. Our earlier work on the monoacyl lipopeptide class of TLR2 agonists led to the design of a highly potent lead, but with negligible aqueous solubility, necessitating the reintroduction of aqueous solubility. We explored several strategies of introducing ionizable groups on the lipopeptide, as well as the systematic evaluation of chemically stable bioisosteres of the ester-linked palmitoyl group. These studies have led to a fully optimized, chemically stable, and highly water-soluble, human TLR2-specific agonist, which was found to have an excellent safety profile and displayed prominent adjuvantic activities in rabbit models.

show abstract

“…The gained experience in innovation, clinical testing, production development, and full production of antisera pushed our team to move next step into vaccine development, maintaining the dedicated enclosed plants, which guarantee hands off from the production staff [5][6][7][8][9][10].…”

Section: Diphtheria Tetanus and Pertussis (Dtp) Vaccinementioning

confidence: 99%

Developing Countries Can Innovate and Produce Vaccines: The Case of Butantan in Brazil

Raw¹

2019

Vaccines - The History and Future

Self Cite

View full text Add to dashboard Cite

Since the introduction of vaccines, governments learn that they are the most efficient and inexpensive tool to avoid the spreading of infectious diseases. It resulted in the creation of public research institutes to develop new vaccines, which gave birth to the vaccine industry, that is, growing in size by acquisition of competitors, which estimate that in 2019 they will sell $58 billion, where developing countries represent 80% of the world population, submitted to be dependent of production and prices from large producers. Incapable or not willing to assume the responsibility to produce, accept to purchase vaccines in bulk for filling and labeling as "producers." Butantan, a public not for profit institute became the first producer of specific anti-venoms and anti-rabies sera. In 1985, Butantan Center of Biotechnology attracted 25 young PhD, which accepted to carry on inovations and technical developments, setting dedicated plants to produce vaccines at affordable cost, aiming self-sufficiency to distribute free through the Ministry of Health. This chapter describes problems and solutions that must be faced to produce vaccine at a cost that developing countries can afford. Keywords: vacines control epidemics, developing coutries 80% of world population, developing countries self-sufficiency, Butantan from innovation to production, anti-venonms and anti-toxinas, encloses production plants, pertussis reduction by DTP vaccine, whole pertussis low in LPS, MPLA from B pertusis as adjuvant, MPLA adjuvant reduce ¼ influenza doses an price of vaccine, vitamines A,D,E, riboflavin as adjuvants, pneumococcus-PSAP3 reduce cost of pneumo vaccine, plasma fractions not for sale, lung surfactant saves neonatals 1. Institute Butantan-research, process development, and production 1.1 Antivenoms and antitoxins Antisnake venoms were the strength of Instituto Butantan and its priority [1-4]. At the New York World Fair, Vital Brazil saved the life of an employee of the Bronx Zoo bitten by a rattlesnake, which induced President Theodore Roosevelt pay a visit to Butantan in 1915. In 1983, Butantan sera production situation was scary: venoms were collected from snakes and administered to horses. The horses were bled and their blood collected in rusted milk drums, precipitated Vaccines-The History and Future 2 with ammonium sulfate, concentrated using a dirty towel, diluted and kept in large bottles until they "mature," and covered with mold! Probable other developing countries producers used the same ancient manufacturing process. Changing the production technology was the first goal of a recent Ph.D. group of researchers supported by the staff from the production laboratories under my supervision (Figures 1-6). The first idea was to replicate the milk industry profile, creating a "hands-off " fully enclosed system using large stainless steel tanks and an industrial plate centrifuge. After snake venom inoculation, horse blood was collected in a 7-liter sterile bag with anticlotting solution, stirred, and kept in a cold room overnight. ...

show abstract

Acellular and "low" pertussis vaccines: adverse events and the role of mutations

Cited by 12 publications

References 12 publications

An improved whole cell pertussis vaccine with reduced content of endotoxin

An improved whole cell pertussis vaccine with reduced content of endotoxin

Design and Development of Stable, Water-Soluble, Human Toll-like Receptor 2 Specific Monoacyl Lipopeptides as Candidate Vaccine Adjuvants

Developing Countries Can Innovate and Produce Vaccines: The Case of Butantan in Brazil

Contact Info

Product

Resources

About