Neutralizing Antibodies to Pertussis Toxin in Whooping Cough

1985 ◽  
Vol 151 (4) ◽  
pp. 646-649 ◽  
Author(s):  
M. Granstrom ◽  
G. Granstrom ◽  
P. Gillenius ◽  
P. Askelof
Keyword(s):  
Pertussis Toxin ◽  
Neutralizing Antibodies ◽  
Whooping Cough

scholarly journals Site-specific alterations in the B oligomer that affect receptor-binding activities and mitogenicity of pertussis toxin.

1993 ◽  
Vol 177 (1) ◽  
pp. 79-87 ◽  
Author(s):  
Y Lobet ◽  
C Feron ◽  
G Dequesne ◽  
E Simoen ◽  
P Hauser ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Pertussis Toxin ◽  
Neutralizing Antibodies ◽  
Whooping Cough ◽  
Site Directed Mutagenesis ◽  
Molar Ratio ◽  
Amino Acid Residues ◽  
Identify Amino Acid ◽  
Generation Vaccine ◽  
Adp Ribosyltransferase

Pertussis toxin plays a major role in the pathogenesis of whooping cough and is considered an important constituent of vaccines against this disease. It is composed of five different subunits associated in a molar ratio 1S1:1S2:1S3:2S4:1S5. The S1 subunit is responsible for the ADP-ribosyltransferase activity of the toxin. The B moiety, composed of S2 through S5, recognizes and binds to the target cell receptors and has some ADP-ribosyltransferase-independent activities such as mitogenicity. Site-directed mutagenesis of subunits S2 and S3 allowed us to identify amino acid residues involved in receptor binding. Of all the modifications generated, the deletion of Asn 105 in S2 and of Lys 105 in S3 resulted in the more drastic reduction of binding to haptoglobin and CHO cells, respectively. A holotoxin carrying both deletions presented a mitogenicity reduced to an undetectable level. The combination of these B oligomer mutations with two substitutions in the S1 subunit led to the production of a toxin analog with reduced ADP-ribosyltransferase-dependent and -independent activities including mitogenicity. As shown by immunoprecipitation with various monoclonal antibodies, the mutant holotoxin was correctly assembled and antigenically similar to the native toxin. This toxin analog induced toxin-neutralizing antibodies at the same level as the holotoxin carrying only mutations in the S1 subunit, and may therefore be considered a useful candidate for the development of a new generation vaccine against whooping cough.

scholarly journals Metabolic, humoral, and cellular responses in adult volunteers immunized with the genetically inactivated pertussis toxin mutant PT-9K/129G.

1990 ◽  
Vol 172 (3) ◽  
pp. 861-868 ◽  
Author(s):  
A Podda ◽  
L Nencioni ◽  
M T De Magistris ◽  
A Di Tommaso ◽  
P Bossù ◽  
...  
Keyword(s):  
T Cells ◽  
Pertussis Toxin ◽  
Neutralizing Antibodies ◽  
Cellular Response ◽  
Genetic Manipulation ◽  
Whooping Cough ◽  
Cellular Responses ◽  
Adult Volunteers

PT-9K/129G, a nontoxic mutant of pertussis toxin (PT) obtained by genetic manipulation, has been shown in animal models to be a promising candidate for new vaccines against whooping cough. To assess the safety and the immunogenicity of PT-9K/129G in humans, a pilot study has been performed in adult volunteers. The protein was found to be safe, capable of inducing high titers of toxin-neutralizing antibodies, and capable of generating immunological memory. In fact, vaccination caused an increase of cell-mediated response to PT, PT-9K/129G, S1 subunit, and B oligomer, indicating that memory T cells are induced by the vaccine. Since PT-9K/129G is mitogenic for T lymphocytes in vitro, it was investigated whether this activity is also present in vivo. No variation was observed in the proportion of T cells (CD3+), T helper cells (CD4+), and cytotoxic T cells (CD8+), as well as in that of other lymphoid populations, by FACS analysis. Interestingly, no thorough correlation was found between humoral and cellular responses. In one case, a very high cellular response was present in absence of detectable antibodies, suggesting that the antibody response, which is the only parameter measured in most clinical trials, may not give a complete picture of the response induced by a vaccine.

SARS-CoV-2 Biology Insights, Part IV.Antibody-Dependent Enhancement (ADE) and the tricky “Herd Immunity”: narrative review (Preprint)

2020 ◽  
Author(s):  
Laura Lafon-Hughes
Keyword(s):  
Viral Infection ◽  
Viral Entry ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Whooping Cough ◽  
Common Knowledge ◽  
Herd Immunity ◽  
Life Quality ◽  
Host Cells ◽  
System P

BACKGROUND It is common knowledge that vaccination has improved our life quality and expectancy since it succeeded in achieving almost eradication of several diseases including chickenpox (varicella), diphtheria, hepatitis A and B, measles, meningococcal, mumps, pneumococcal, polio, rotavirus, rubella, tetanus and whooping cough (pertussis) Vaccination success is based on vaccine induction of neutralizing antibodies that help fight the infection (e.g. by a virus), preventing the disease. Conversely, Antibody-dependent enhancement (ADE) of a viral infection occurs when anti-viral antibodies facilitate viral entry into host cells and enhance viral infection in these cells. ADE has been previously studied in Dengue and HIV viruses and explains why a second infection with Dengue can be lethal. As already reviewed in Part I and Part II, SARS-Cov-2 shares with HIV not only 4 sequences in the Spike protein but also the capacity to attack the immune system. OBJECTIVE As HIV presents ADE, we wondered whether this was also the case regarding SARS-CoV-2. METHODS A literature review was done through Google. RESULTS SARS-CoV-2 presents ADE. As SARS, which does not have the 4 HIV-like inserts, has the same property, ADE would not be driven by the HIV-like spike sequences. CONCLUSIONS ADE can explain the failure of herd immunity-based strategies and will also probably hamper anti-SARS-CoV-2 vaccine development. As reviewed in Part I, there fortunately are promising therapeutic strategies for COVID-19, which should be further developed. In the meantime, complementary countermeasures to protect mainly the youth from this infection are presented to be discussed in Part V Viewpoint.

scholarly journals Pharmacological targeting of host chaperones protects from pertussis toxin in vitro and in vivo

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Katharina Ernst ◽  
Ann-Katrin Mittler ◽  
Veronika Winkelmann ◽  
Carolin Kling ◽  
Nina Eberhardt ◽  
...  
Keyword(s):  
Pertussis Toxin ◽  
Airway Epithelium ◽  
Whooping Cough ◽  
Apical Surface ◽  
Basal Cells ◽  
Pharmacological Chaperone ◽  
Infant Mouse ◽  
Novel Therapeutic Strategies

AbstractWhooping cough is caused by Bordetella pertussis that releases pertussis toxin (PT) which comprises enzyme A-subunit PTS1 and binding/transport B-subunit. After receptor-mediated endocytosis, PT reaches the endoplasmic reticulum from where unfolded PTS1 is transported to the cytosol. PTS1 ADP-ribosylates G-protein α-subunits resulting in increased cAMP signaling. Here, a role of target cell chaperones Hsp90, Hsp70, cyclophilins and FK506-binding proteins for cytosolic PTS1-uptake is demonstrated. PTS1 specifically and directly interacts with chaperones in vitro and in cells. Specific pharmacological chaperone inhibition protects CHO-K1, human primary airway basal cells and a fully differentiated airway epithelium from PT-intoxication by reducing intracellular PTS1-amounts without affecting cell binding or enzyme activity. PT is internalized by human airway epithelium secretory but not ciliated cells and leads to increase of apical surface liquid. Cyclophilin-inhibitors reduced leukocytosis in infant mouse model of pertussis, indicating their promising potential for developing novel therapeutic strategies against whooping cough.

Purification and immunological characterization of HPLC-purified pertussis toxin subunits

1991 ◽  
Vol 69 (5-6) ◽  
pp. 336-340
Author(s):  
Pele Chong ◽  
Stephen Cockle ◽  
Heather Boux ◽  
Michel Klein
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Pertussis Toxin ◽  
High Performance ◽  
Whooping Cough ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Active Immunization ◽  
Single Step ◽  
Nad Glycohydrolase

Pertussis toxin (PT), an oligomeric exotoxin of Bordetella pertussis containing five dissimilar subunits, is considered to be an essential immunogen in acellular and component pertussis vaccines against whooping cough. A rapid single-step procedure for isolating PT subunits was developed using reverse-phase high-performance liquid chromatography. Recoveries of individual subunits were 75% (S1), 70% (S2), > 90% (S3), > 90% (S4), and 50% (S5), as judged by SDS-PAGE and amino acid analysis. Lyophilized subunits were solubilized in urea followed by step-wise dialysis to remove the urea. All subunits were inactive in histamine sensitization, lymphocytosis, and hemagglutination assays. However, purified S1 retained residual NAD-glycohydrolase and ADP-ribosyltransferase activity. A partially active holotoxin could be generated by mixing the five individual subunits. All subunits were immunogenic in rabbits and mice. Monospecific antisera raised in both animal species were able to neutralize the PT-mediated clustering of Chinese hamster ovary cells, but active immunization of mice with single subunits failed to protect them in the intracerebral challenge assay. These subunit preparations therefore retained neutralizing determinants, but did not contain protective epitopes.Key words: pertussis toxin, high-performance liquid chromatography, purification, pertussis vaccine.

scholarly journals A cocktail of humanized anti–pertussis toxin antibodies limits disease in murine and baboon models of whooping cough

2015 ◽  
Vol 7 (316) ◽  
pp. 316ra195-316ra195 ◽  
Author(s):  
Annalee W. Nguyen ◽  
Ellen K. Wagner ◽  
Joshua R. Laber ◽  
Laura L. Goodfield ◽  
William E. Smallridge ◽  
...  
Keyword(s):  
Pertussis Toxin ◽  
Whooping Cough

scholarly journals Pertussis Toxin: A Key Component in Pertussis Vaccines?

Toxins ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 557
Author(s):  
Kelsey A. Gregg ◽  
Tod J. Merkel
Keyword(s):  
Immune Responses ◽  
Pertussis Toxin ◽  
Whooping Cough ◽  
Protective Role ◽  
Clear Understanding ◽  
Correlates Of Protection ◽  
Vaccine Antigens ◽  
Specific Pathogen ◽  
Human Specific

B. pertussis is a human-specific pathogen and the causative agent of whooping cough. The ongoing resurgence in pertussis incidence in high income countries is likely due to faster waning of immunity and increased asymptomatic colonization in individuals vaccinated with acellular pertussis (aP) vaccine relative whole-cell pertussis (wP)-vaccinated individuals. This has renewed interest in developing more effective vaccines and treatments and, in support of these efforts, defining pertussis vaccine correlates of protection and the role of vaccine antigens and toxins in disease. Pertussis and its toxins have been investigated by scientists for over a century, yet we still do not have a clear understanding of how pertussis toxin (PT) contributes to disease symptomology or how anti-PT immune responses confer protection. This review covers PT’s role in disease and evidence for its protective role in vaccines. Clinical data suggest that PT is a defining and essential toxin for B. pertussis pathogenesis and, when formulated into a vaccine, can prevent disease. Additional studies are required to further elucidate the role of PT in disease and vaccine-mediated protection, to inform the development of more effective treatments and vaccines.

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