scholarly journals Next-Generation Pertussis Vaccines Based on the Induction of Protective T Cells in the Respiratory Tract

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 621 ◽  
Author(s):  
Caitlín Ní Chasaide ◽  
Kingston H.G. Mills
Keyword(s):  
Respiratory Tract ◽  
Protective Immunity ◽  
Membrane Vesicle ◽  
Secretory Iga ◽  
Nasal Colonization ◽  
Next Generation ◽  
Previous Infection ◽  
Cellular Immune

Immunization with current acellular pertussis (aP) vaccines protects against severe pertussis, but immunity wanes rapidly after vaccination and these vaccines do not prevent nasal colonization with Bordetella pertussis. Studies in mouse and baboon models have demonstrated that Th1 and Th17 responses are integral to protective immunity induced by previous infection with B. pertussis and immunization with whole cell pertussis (wP) vaccines. Mucosal Th17 cells, IL-17 and secretory IgA (sIgA) are particularly important in generating sustained sterilizing immunity in the nasal cavity. Current aP vaccines induce potent IgG and Th2-skewed T cell responses but are less effective at generating Th1 and Th17 responses and fail to prime respiratory tissue-resident memory T (TRM) cells, that maintain long-term immunity at mucosal sites. In contrast, a live attenuated pertussis vaccine, pertussis outer membrane vesicle (OMV) vaccines or aP vaccines formulated with novel adjuvants do induce cellular immune responses in the respiratory tract, especially when delivered by the intranasal route. An increased understanding of the mechanisms of sustained protective immunity, especially the role of respiratory TRM cells, will facilitate the development of next generation pertussis vaccines that not only protect against pertussis disease, but prevent nasal colonization and transmission of B. pertussis.

The immunology of Bordetella pertussis infection and vaccination

Pertussis ◽  
2018 ◽  
pp. 42-65
Author(s):  
Mieszko M. Wilk ◽  
Aideen C. Allen ◽  
Alicja Misiak ◽  
Lisa Borkner ◽  
Kingston H.G. Mills
Keyword(s):  
Bordetella Pertussis ◽  
Whooping Cough ◽  
Vaccine Coverage ◽  
Immunological Memory ◽  
Nasal Colonization ◽  
Pertussis Infection ◽  
Genetic Changes ◽  
Antibody Titres ◽  
Previous Infection ◽  
Cellular Immune

Bordetella pertussis causes whooping cough (pertussis), a severe and sometimes fatal respiratory infectious disease, especially in young infants. Pertussis can be prevented in infants and children by immunization with either whole-cell pertussis (wP) or acellular pertussis (aP) vaccines; however, its incidence is increasing in many countries despite high vaccine coverage. This resurgence in populations immunized with aP vaccines has been attributed to (1) genetic changes in circulating strains of B. pertussis resulting from vaccine-driven immune selection, (2) waning protective immunity due to poor induction of immunological memory, or (3) a failure of aP vaccines to induce the appropriate arm(s) of the cellular immune responses required to prevent infection. Studies in a baboon model have suggested that previous infection prevents reinfection as well as disease, whereas aP vaccines fail to prevent nasal colonization and transmission of B. pertussis. Studies in the mouse model have demonstrated that immunization with wP vaccines induces Th1 and Th17 responses, whereas aP vaccines promote Th2-skewed responses and high antibody titres. Thus, while aP vaccine-induced antibodies may prevent pertussis, they may not prevent nasal colonization or transmission. Emerging data have suggested that replacing alum with novel adjuvants based on pathogen-associated molecular patterns has the capacity to switch the responses induced with aP vaccines to the more protective Th1/Th17 responses and may also enhance immunological memory. It is likely that third-generation pertussis vaccines will be based on live attenuated bacteria or aP formulations with novel adjuvants, which prevent nasal and lung infection and induce sustained immunity through induction of memory T cells.

scholarly journals Motivation and challenge to capture both large-scale and local transport in next generation accretion theory

2015 ◽  
Vol 81 (5) ◽  
Author(s):  
Eric G. Blackman ◽  
Farrukh Nauman
Keyword(s):  
Field Theory ◽  
Large Scale ◽  
Mean Field Theory ◽  
Mean Field ◽  
Next Generation ◽  
Dynamo Theory ◽  
Non Local ◽  
Local Transport

Accretion disc theory is less developed than stellar evolution theory although a similarly mature phenomenological picture is ultimately desired. While the interplay of theory and numerical simulations has amplified community awareness of the role of magnetic fields in angular momentum transport, there remains a long term challenge to incorporate the insights gained from simulations into improving practical models for comparison with observations. What has been learned from simulations that can lead to improvements beyond SS73 in practical models? Here, we emphasize the need to incorporate the role of non-local transport more precisely. To show where large-scale transport would fit into the theoretical framework and how it is currently missing, we review why the wonderfully practical approach of Shakura & Sunyaev (Astron. Astrophys., vol. 24, 1973, pp. 337–355, SS73) is necessarily a mean field theory, and one which does not include large-scale transport. Observations of coronae and jets, combined with the interpretation of results from shearing box simulations, of the magnetorotational instability (MRI) suggest that a significant fraction of disc transport is indeed non-local. We show that the Maxwell stresses in saturation are dominated by large-scale contributions and that the physics of MRI transport is not fully captured by a viscosity. We also clarify the standard physical interpretation of the MRI as it applies to shearing boxes. Computational limitations have so far focused most attention toward local simulations, but the next generation of global simulations should help to inform improved mean field theories. Mean field accretion theory and mean field dynamo theory should in fact be unified into a single theory that predicts the time evolution of spectra and luminosity from separate disc, corona and outflow contributions. Finally, we note that any mean field theory, including that of SS73, has a finite predictive precision that needs to be quantified when comparing the predictions to observations.

Long-Term Consequences of Foodborne Toxoplasmosis: Effects on the Unborn, the Immunocompromised, the Elderly, and the Immunocompetent†

1997 ◽  
Vol 60 (12) ◽  
pp. 1595-1611 ◽  
Author(s):  
JAMES L. SMITH
Keyword(s):  
At Risk ◽  
Immune System ◽  
Congenital Toxoplasmosis ◽  
Protozoan Parasite ◽  
The Elderly ◽  
The Body ◽  
Cell Mediated Immunity ◽  
Previous Infection ◽  
Cellular Immune

In immunointact individuals, infection by the ubiquitous protozoan parasite Toxoplasma gondii is common, but clinical disease is rare; however, fetal and immunocompromised populations are at risk for clinical toxoplasmosis. T. gondii organisms persist as quiescent tissue cysts in various tissues of the body with the possibility of tissue cysts reactivating to actively multiplying parasites if there is a decline in the infected individual's immune system. In more recent years, there has been an increase in toxoplasmosis due to a steadily increasing immunocompromised population. T. gondii infections are controlled principally by the cellular immune system. Thus, individuals with defective cell-mediated immunity cannot control a T. gondii infection and if they have been infected previously, reactivation of a previous infection may occur. Congenital toxoplasmosis can cause severe complications in the fetuses of women who are infected with T. gondii during pregnancy. Toxoplasmosis can be serious in individuals with malignancies or AIDS. Since transplant recipients are immunosuppressed by drug treatment, they too are at risk for toxoplasmosis if they receive an organ from an infected donor. Vaccines against T. gondii suitable for human use have not been developed. No drug is available that can eliminate the encysted stage of the parasite; thus, infected individuals are always at risk for reactivation of the parasite if there is a failure of their immune system. More emphasis should be placed on the elimination of T. gondii by development of drugs which can eliminate the cyst stage in tissues and on development of vaccines suitable for protecting humans against infection or reactivation.

scholarly journals Extended interval BNT162b2 vaccination enhances peak antibody generation in older people

2021 ◽  
Author(s):  
Helen M Parry ◽  
Rachel Bruton ◽  
Christine Stephens ◽  
Kevin Brown ◽  
Gayatri Amirthalingam ◽  
...  
Keyword(s):  
Immune Responses ◽  
Older People ◽  
Population Based ◽  
Cellular Immune Responses ◽  
Previous Infection ◽  
Clinical Protection ◽  
Cellular Immune ◽  
Matched Samples

Abstract Objectives: To assess the relative immunogenicity of standard or extended interval BNT162b2 vaccination. Design: Population based cohort study comparing immune responses 2 weeks after the second vaccine, with appropriate time-matched samples in participants who received standard or extended interval double vaccination. Setting: Primary care networks, Birmingham, UK. December 2020 to April 2021. Participants: 175 people aged over 80 years of age. All donors received the BNT162b2 Pfizer/BioNTech vaccination and were vaccinated with either a standard 3 week interval between doses or an extended interval schedule. Main outcome measures: Peak quantitative spike-specific antibody and cellular immune responses. Results: In donors without evidence of previous infection the peak antibody response was 3.5-fold higher in donors who had undergone delayed interval vaccination. Cellular immune responses were 3.6-fold lower. Conclusion: Peak antibody responses after the second BNT162b2 vaccine are markedly enhanced in older people when this is delayed to 12 weeks although cellular responses are lower. Extended interval vaccination may therefore offer the potential to enhance and extend humoral immunity. Further follow up is now required to assess long term immunity and clinical protection.

scholarly journals Possible Correlates of Long-Term Protection against Helicobacter pylori following Systemic or Combinations of Mucosal and Systemic Immunizations

2007 ◽  
Vol 75 (7) ◽  
pp. 3462-3469 ◽  
Author(s):  
Jennifer M. Taylor ◽  
Melanie E. Ziman ◽  
Julie Fong ◽  
Jay V. Solnick ◽  
Michael Vajdy
Keyword(s):  
Helicobacter Pylori ◽  
Protective Immunity ◽  
Interleukin 12 ◽  
Effective Vaccine ◽  
Correlates Of Protection ◽  
Oral Group ◽  
Efficient Route ◽  
H Pylori

ABSTRACT The ability to induce long-term immunity to Helicobacter pylori is necessary for an effective vaccine. This study was designed to establish the most efficient route(s) (systemic, mucosal, or a combination) of immunization for induction of long-term immunity and to define correlates of protection. Mice were immunized orally alone (oral group), intramuscularly (i.m.) alone (i.m. group), orally followed by i.m. (oral/i.m. group), or i.m. followed by orally (i.m./oral group). Long-term protective immunity to oral H. pylori challenge was observed 3 months after immunization through the i.m. or oral/i.m. route. Protection correlated with an increase in H. pylori-specific interleukin-12 and both immunoglobulin G1 (IgG1) and IgG2a serum titers following challenge. Mice that were not protected (oral or i.m./oral) had increased levels of IgA in both sera and Peyer's patches. This study demonstrates the ability to induce long-term immunity against H. pylori, provides correlates of protection, and illustrates the crucial role of the immunization route(s).

scholarly journals CNLAC1 Is Required for Extrapulmonary Dissemination of Cryptococcus neoformans but Not Pulmonary Persistence

2004 ◽  
Vol 72 (3) ◽  
pp. 1693-1699 ◽  
Author(s):  
Mairi C. Noverr ◽  
Peter R. Williamson ◽  
Ryan S. Fajardo ◽  
Gary B. Huffnagle
Keyword(s):  
Respiratory Tract ◽  
Cryptococcus Neoformans ◽  
Random Mutagenesis ◽  
Pathogenic Yeast ◽  
Infectious Dose ◽  
Cellular Immune Responses ◽  
Laccase Enzyme ◽  
Cellular Immune ◽  
The Brain

ABSTRACT The pathogenic yeast Cryptococcus neoformans produces a laccase enzyme (CNLAC1), which catalyzes the synthesis of melanin in the presence of phenolic compounds. A number of genes have been implicated in the regulation of laccase and melanization, including IPC1, GPA1, MET3, and STE12. Albino mutants derived from random mutagenesis techniques may contain mutations in genes that regulate multiple virulence factors, including CNLAC1. The goal of our study is to investigate the role of CNLAC1 in virulence and evasion of pulmonary host defenses after infection via the respiratory tract. Using a set of congenic laccase-positive (2E-TUC-4) and laccase-deficient (2E-TU-4) strains, we found that both strains are avirulent at a lower dose (104 CFU/mouse) in mice. After the infectious dose was increased to 106 CFU/mouse, 70% mortality was observed in mice infected with 2E-TUC-4 compared to no mortality in mice infected with 2E-TU-4 at day 30 postinfection. This observation confirms the requirement for CNLAC1 in virulence. Interestingly, we observed no differences between the two strains in pulmonary growth or in elicitation of cellular immune responses in the lung. The only measurable defect of 2E-TU-4 was in dissemination to extrapulmonary sites. To examine the role of CNLAC1 in dissemination, mice were infected intravenously. By week 3 postinfection, equal numbers of strains 2E-TUC-4 and 2E-TU-4 were recovered from the brain and spleen. This observation indicates that CNLAC1 facilitates escape from the lung, but not growth in the lungs or brain, and suggests a novel role for CNLAC1 in virulence during an infection aquired via the respiratory tract.

scholarly journals In the Absence of CD154, Administration of Interleukin-12 Restores Th1 Responses but Not Protective Immunity to Schistosoma mansoni

2007 ◽  
Vol 75 (7) ◽  
pp. 3539-3547 ◽  
Author(s):  
James P. Hewitson ◽  
Paul A. Hamblin ◽  
Adrian P. Mountford
Keyword(s):  
Lymph Nodes ◽  
Protective Immunity ◽  
Interleukin 12 ◽  
Cell Mediated Immunity ◽  
Mhc Ii ◽  
Histocompatibility Complex ◽  
Cellular Immune ◽  
Antigen Presenting ◽  
Induced Immunity

ABSTRACT The cytokine interplay during the development of protective immunity to the radiation-attenuated (RA) schistosome vaccine has been extensively characterized over recent years, yet the role of costimulatory molecules in the development of cell-mediated immunity is much less well understood. Here we demonstrate the importance of CD40/CD154 in vaccine-induced immunity, as CD154−/− mice exposed to RA schistosomes develop no protection to challenge infection. We showed that vaccinated CD154−/− mice have defective Th1-associated immune responses in the skin-draining lymph nodes and the lungs, with reduced or absent levels of interleukin-12p40 (IL-12p40), gamma interferon, and nitric oxide, but elevated levels of lung IL-4 and IL-5. The expression of major histocompatibility complex II (MHC-II) on antigen-presenting cells recovered from the lungs of vaccinated CD154−/− mice was also severely compromised. The administration of anti-CD40 monoclonal antibody (MAb) to CD154−/− mice did not reconstitute sustained Th1 responses in the lymph nodes or the lungs, nor did the MAb restore anti-parasite immunoglobulin G production or protective immunity. On the other hand, the administration of recombinant IL-12 (rIL-12) to CD154−/− mice shortly after vaccination caused elevated and sustained levels of Th1-associated cytokines, rescued MHC-II expression by lung CD11c+ cells, and restored the appearance of inflammatory effector foci in the lungs. However, the treatment of CD154−/− mice with rIL-12 did not restore protection. We conclude that protective immunity to the RA schistosome vaccine is CD154 dependent but is independent of IL-12-orchestrated cellular immune mechanisms in the lungs.

scholarly journals Leptin in the Respiratory Tract: Is There a Role in SARS-CoV-2 Infection?

2021 ◽  
Vol 12 ◽  
Author(s):  
Andreina Bruno ◽  
Giuliana Ferrante ◽  
Serena Di Vincenzo ◽  
Elisabetta Pace ◽  
Stefania La Grutta
Keyword(s):  
Respiratory Tract ◽  
Protective Immunity ◽  
Immune Modulation ◽  
Pulmonary Infections ◽  
Peripheral Tissues ◽  
Innate And Adaptive Immunity ◽  
Leptin Receptors ◽  
Leptin Sensitivity ◽  
Lung Health

Leptin is a pleiotropic adipocytokine involved in several physiologic functions, with a known role in innate and adaptive immunity as well as in tissue homeostasis. Long- and short-isoforms of leptin receptors are widely expressed in many peripheral tissues and organs, such as the respiratory tract. Similar to leptin, microbiota affects the immune system and may interfere with lung health through the bidirectional crosstalk called the “gut-lung axis.” Obesity leads to impaired protective immunity and altered susceptibility to pulmonary infections, as those by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although it is known that leptin and microbiota link metabolism and lung health, their role within the SARS-CoV2 coronavirus disease 2019 (COVID-19) deserves further investigations. This review aimed to summarize the available evidence about: (i) the role of leptin in immune modulation; (ii) the role of gut microbiota within the gut-lung axis in modulating leptin sensitivity; and (iii) the role of leptin in the pathophysiology of COVID-19.

scholarly journals Protective humoral and cellular immune responses to SARS-CoV-2 persist up to 1 year after recovery

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chengqian Feng ◽  
Jingrong Shi ◽  
Qinghong Fan ◽  
Yaping Wang ◽  
Huang Huang ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Critical Factor ◽  
Population Level ◽  
Effective Population ◽  
Cellular Immune Responses ◽  
Neutralizing Capacity ◽  
One Year ◽  
Cellular Immune ◽  
Kinetics Of

AbstractSARS-CoV-2 vaccination has been launched worldwide to build effective population-level immunity to curb the spread of this virus. The effectiveness and duration of protective immunity is a critical factor for public health. Here, we report the kinetics of the SARS-CoV-2 specific immune response in 204 individuals up to 1-year after recovery from COVID-19. RBD-IgG and full-length spike-IgG concentrations and serum neutralizing capacity decreases during the first 6-months, but is maintained stably up to 1-year after hospital discharge. Even individuals who had generated high IgG levels during early convalescent stages had IgG levels that had decreased to a similar level one year later. Notably, the RBD-IgG level positively correlates with serum neutralizing capacity, suggesting the representative role of RBD-IgG in predicting serum protection. Moreover, viral-specific cellular immune protection, including spike and nucleoprotein specific, persisted between 6 months and 12 months. Altogether, our study supports the persistence of viral-specific protective immunity over 1 year.

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