scholarly journals The Path to New Pediatric Vaccines against Pertussis

Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 228
Author(s):  
Camille Locht
Keyword(s):  
Whooping Cough ◽  
Disease Incidence ◽  
Age Groups ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Pertussis Infection ◽  
Live Attenuated Vaccine ◽  
Administration Routes ◽  
Immunogenicity Assessment ◽  
Acellular Vaccines

Whooping cough, or pertussis, mostly caused by Bordetella pertussis, is a respiratory disease that affects all age groups, but severe and fatal pertussis occurs almost exclusively in young children. The widespread use of whole-cell and, more recently, of acellular vaccines has substantially reduced the disease incidence. However, it has not been eliminated in any part of the world and has made a worrisome rebound in several areas. Cocoon and maternal immunization have been implemented in several countries but have their intrinsic limitations. To effectively control pertussis, novel vaccines are needed that protect against disease and prevent B. pertussis infection and transmission, which is not the case for current vaccines. Several approaches are contemplated, including alternative administration routes, such as nasal immunization, improvement of acellular vaccines by adding more antigens and T-cell-promoting adjuvants, and the development of novel vaccines, such as outer membrane vesicles and live attenuated vaccines. Among them, only a live attenuated vaccine has so far been assessed for safety and immunogenicity in preclinical models other than mice and is in clinical development. Before any of these vaccines can be used in neonates, extensive safety and immunogenicity assessment in pre-clinical neonatal models and in carefully designed clinical trials is necessary. The aim of this review is to discuss the current pertussis problem, implemented strategies to resolve it, the value of animal models and novel vaccine approaches.

CLINICAL AND LABORATORY PECULIARITIES OF WHOOPING COUGH IN CHILDREN OF DIFFERENT AGE GROUPS

2020 ◽  
Vol 99 (6) ◽  
pp. 98-104
Author(s):  
I.V. Babachenko ◽  
◽  
Y.V. Nesterova ◽  
N.V. Skripchenko ◽  
◽  
...  
Keyword(s):  
Whooping Cough ◽  
Severe Disease ◽  
Respiratory Rhythm ◽  
Age Groups ◽  
Low Frequency ◽  
Pertussis Infection ◽  
Group 2 ◽  
Sick Children ◽  
Hematological Changes ◽  
Group 1

Objective of the research: to present the clinical and laboratory peculiarities of modern whooping cough in hospitalized children of different ages. Materials and methods: сlinical and laboratory characteristics of whooping cough were analyzed in 88 hospitalized sick children aged 1 month to 18 years in groups of children: group 1 – children under 1 year old; group 2 – children 1–6 years old; group 3 – children 7–17 years old. DNA of causative agents of pertussis infection was isolated by PCR in nasopharyngeal swabs using a commercial kit AmpliSens®Bordetella multi-FL (Moscow). Results: children of group 1 in 90% (n=43) of cases were not vaccinated against whooping cough, severe forms were recorded in 17% (n=8) of children of the 1st year of life, and in 15% (n=7) – due to respiratory rhythm disturbances. The diagnosis was confirmed by PCR in 94% (n=45) of children, leukocytosis with lymphocytosis was detected in 81,5% (n=101). Along with hematological changes typical for whooping cough, 79% (n=38) of patients in the first year of life had thrombocytosis (>400×109/l), which was most pronounced in severe disease course 511,5 [425; 568,5]×109/l vs 421 [347; 505,5]×109/l; p<0,05, which has no tendency to decrease throughout the entire observation period and correlates with the level of leukocytes (rs=0,69; p<0,001). Patients over 7 years old in 88% (n=21) of cases were vaccinated against whooping cough, but 79% (n=27) hemograms had no characteristic changes, which, along with a low frequency of confirmation of the diagnosis by PCR 22% (n=4), made it difficult to diagnose whooping cough. Conclusion: children over 7 years of age may not have characteristic hematological changes and PCR diagnostics are insufficiently effective, which contributes to the spread of whooping cough in family foci.

scholarly journals ZnuD, a Potential Candidate for a Simple and Universal Neisseria meningitidis Vaccine

2013 ◽  
Vol 81 (6) ◽  
pp. 1915-1927 ◽  
Author(s):  
Kerstin Hubert ◽  
Nathalie Devos ◽  
Ines Mordhorst ◽  
Christine Tans ◽  
Guy Baudoux ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Outer Membrane ◽  
Age Groups ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Potential Candidate ◽  
Content Type ◽  
Homologous Protein ◽  
Vaccine Antigens ◽  
Type Strains

ABSTRACTNeisseria meningitidisserogroup B (MenB) is a major cause of bacterial sepsis and meningitis, with the highest disease burden in young children. Available vaccines are based on outer membrane vesicles (OMVs) obtained from wild-type strains. However, particularly in toddlers and infants, they confer protection mostly against strains expressing the homologous protein PorA, a major and variable outer membrane protein. In the quest for alternative vaccine antigens able to provide broad MenB strain coverage in younger populations, but potentially also across all age groups, ZnuD, a protein expressed under zinc-limiting conditions, may be considered a promising candidate. Here, we have investigated the potential value of ZnuD and show that it is a conserved antigen expressed by all MenB strains tested except for some strains of clonal complex ST-8. In mice and guinea pigs immunized with ZnuD-expressing OMVs, antibodies were elicited that were able to trigger complement-mediated killing of all the MenB strains and serogroup A, C, and Y strains tested when grown under conditions of zinc limitation. ZnuD is also expressed during infection, since anti-ZnuD antibodies were detected in sera from patients. In conclusion, we confirm the potential of ZnuD-bearing OMVs as a component of an effective MenB vaccine.

scholarly journals Extraction of Outer membrane Vesicles from Vaccinal Strain of Bordetella Pertussis as the First Step of a Vaccine Candidate Study Against Pertussis Infection

2020 ◽  
Vol 14 (3) ◽  
pp. 213-226
Author(s):  
Maryam Sadat Soltani ◽  
Fereshteh Eftekhar ◽  
Fereshteh Shahcheraghi ◽  
Mojtaba Noofeli ◽  
Seyed Reza Banihashemi ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Bordetella Pertussis ◽  
Vaccine Candidate ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Pertussis Infection ◽  
Vaccinal Strain

scholarly journals Comparison of Immune Responses to Gonococcal PorB Delivered as Outer Membrane Vesicles, Recombinant Protein, or Venezuelan Equine Encephalitis Virus Replicon Particles

2005 ◽  
Vol 73 (11) ◽  
pp. 7558-7568 ◽  
Author(s):  
Weiyan Zhu ◽  
Christopher E. Thomas ◽  
Ching-ju Chen ◽  
Cornelius N. Van Dam ◽  
Robert E. Johnston ◽  
...  
Keyword(s):  
Immune Responses ◽  
Outer Membrane ◽  
Membrane Vesicles ◽  
Binding Activity ◽  
Outer Membrane Vesicles ◽  
Interferon Response ◽  
Enzyme Linked Immunosorbent Assay ◽  
Venezuelan Equine Encephalitis ◽  
Administration Routes ◽  
Dorsal Area

ABSTRACT Porin (PorB) is a major outer membrane protein produced by all Neisseria gonorrhoeae strains and has been a focus of intense interest as a vaccine candidate. In this study, the immunogenicity of PorB in mice was investigated after several immunization regimens. Outer membrane vesicles (OMV), recombinant renatured PorB (rrPorB), and PorB-expressing Venezuelan equine encephalitis (VEE) virus replicon particles (PorB VRP) were delivered intranasally (i.n.) or subcutaneously (s.c.) into the dorsal area or the hind footpad in three-dose schedules; the PorB VRP-immunized mice were given a single additional booster dose of rrPorB in Ribi adjuvant. Different delivery systems and administration routes induced different immune responses. Mice immunized s.c. with rrPorB in Ribi had the highest levels of PorB-specific serum immunoglobulin G (IgG) by enzyme-linked immunosorbent assay. Surprisingly, there was an apparent Th1 bias, based on IgG1/IgG2a ratios, after immunization with rrPorB in Ribi in the footpad while the same vaccine given in the dorsal area gave a strongly Th2-biased response. PorB VRP-immunized mice produced a consistent Th1 response with a high gamma interferon response in stimulated splenic lymphocytes and very low IgG1/IgG2a ratios. Immunization by OMV delivered i.n. was the only regimen that resulted in a serum bactericidal response, and it generated an excellent mucosal IgA response. Serum from mice immunized with rrPorB preferentially recognized the surface of whole gonococci expressing a homologous PorB, whereas serum from PorB VRP-immunized mice had relatively low whole-cell binding activity but recognized both heterologous and homologous PorB equally. The data resulting from this direct comparison suggested that important aspects of the immune response can be manipulated by altering the form of the antigen and its delivery. This information coupled with an understanding of protective antigonococcal immune responses will enable the design of the optimal vaccine for N. gonorrhoeae.

scholarly journals Pertussis infection in adolescents and adults with persistent cough: A Review

2011 ◽  
Vol 5 (1) ◽  
pp. 31-34
Author(s):  
Kazi Yesmin
Keyword(s):  
Diagnostic Tests ◽  
Whooping Cough ◽  
Age Groups ◽  
Respiratory Tract Disease ◽  
Recent Past ◽  
Pertussis Infection ◽  
Atypical Symptoms ◽  
The World ◽  
Adolescents And Adults ◽  
Tract Disease

Pertussis or whooping cough, generally considered as the disease of infants and children, is an acute respiratory tract disease responsible for around 300,000 deaths annually. However, recent reports from many countries of the world clearly indicate that people of all age groups including adolescent and adults could be suffering from this disease. Pertussis remains an underestimated and under reported disease in adolescent and adults due to atypical symptoms in these age groups. Moreover, pertussis has been re-discovered as a frequent cause of prolonged cough in adolescents and adults in the recent past but the diagnosis still is often missed unless specific diagnostic tests are applied. The affected adolescents and adults act as reservoirs of the disease to the vulnerable population of infants. There have been increasing reports of pertussis outbreaks in adults’ population in many western countries and vaccination of this group is being planned. Additional booster doses of acellular pertussis vaccine may help to control and prevent pertussis.DOI: http://dx.doi.org/10.3329/bjmm.v5i1.15819 Bangladesh J Med Microbiol 2011; 05 (01): 31-34

Electrophysiological Characterization of Transport Across Outer Membrane Channels from Gram-Negative Bacteria in Their Native Environment

2019 ◽  
Author(s):  
Jiajun Wang ◽  
Rémi Terrasse ◽  
Jayesh Arun Bafna ◽  
Lorraine Benier ◽  
Mathias Winterhalter
Keyword(s):  
Outer Membrane ◽  
Lipid Membrane ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Multi Drug Resistance ◽  
Gram Negative Bacteria ◽  
Membrane Channels ◽  
Gram Negative ◽  
Electrophysiological Characterization

Multi-drug resistance in Gram-negative bacteria is often associated with low permeability of the outer membrane. To investigate the role of membrane channels in the uptake of antibiotics, we extract, purify and reconstitute them into artificial planar membranes. To avoid this time-consuming procedure, here we show a robust approach using fusion of native outer membrane vesicles (OMV) into planar lipid bilayer which moreover allows also to some extend the characterization of membrane protein channels in their native environment. Two major membrane channels from <i>Escherichia coli</i>, OmpF and OmpC, were overexpressed from the host and the corresponding OMVs were collected. Each OMV fusion revealed surprisingly single or only few channel activities. The asymmetry of the OMV´s translates after fusion into the lipid membrane with the LPS dominantly present at the side of OMV addition. Compared to conventional reconstitution methods, the channels fused from OMVs containing LPS have similar conductance but a much broader distribution. The addition of Enrofloxacin on the LPS side yields somewhat higher association (<i>k<sub>on</sub></i>) and lower dissociation (<i>k<sub>off</sub></i>) rates compared to LPS-free reconstitution. We conclude that using outer membrane vesicles is a fast and easy approach for functional and structural studies of membrane channels in the native membrane.

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