The human immune responses to pertussis and pertussis vaccines

Pertussis ◽  
2018 ◽  
pp. 112-132
Author(s):  
Françoise Mascart ◽  
Violette Dirix ◽  
Camille Locht
Keyword(s):  
Immune Responses ◽  
First Generation ◽  
Placental Transfer ◽  
Whooping Cough ◽  
Natural Infection ◽  
Severe Disease ◽  
T Cell Response ◽  
Comparable Efficacy ◽  
Industrialized Countries ◽  
Human Immune

Two types of pertussis vaccines are currently available: the first-generation, whole-cell (wP) and more recent, acellular (aP) vaccines. The aP vaccine has replaced the wP vaccine in most industrialized countries, based on an improved safety profile and comparable efficacy of the former compared to the latter. As both vaccines, as well as prior infection, protect well against whooping cough disease, albeit by different mechanisms, the human immune responses to natural infection and vaccination have been extensively studied over the last decades. Shortly after the discovery of the causative agent Bordetella pertussis, both agglutinating antibodies and complement-binding antibodies have been identified in the serum of convalescent patients. However, how much they contribute to protection against disease or infection is still not known. Nevertheless, passive transfer of convalescent serum can significantly attenuate the disease and placental transfer of maternal antibodies induced by vaccination during pregnancy has recently been shown to provide strong protection against severe disease in the offspring. Natural infection and wP vaccination have both been shown to induce a strong Th-1-oriented T-cell response, whereas administration of aP vaccine shifts the response to a Th-2 profile, which may be a reason for the fast waning of immunity upon aP vaccination, compared to wP vaccination and natural infection. None of the current vaccines induce sterilizing immunity and limit circulation of B. pertussis. Therefore, new vaccines are needed that protect both against disease and infection. One such candidate, live attenuated BPZE1, designed to prevent B. pertussis infection, is currently in clinical development.

scholarly journals Two doses of SARS-CoV-2 vaccination induce more robust immune responses to emerging SARS-CoV-2 variants of concern than does natural infection.

2021 ◽  
Author(s):  
Donal T. Skelly ◽  
Adam C. Harding ◽  
Javier Gilbert-Jaramillo ◽  
Michael L. Knight ◽  
Stephanie Longet ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Natural Infection ◽  
Vaccine Dose ◽  
T Cell Responses ◽  
T Cell Response ◽  
Potential Threat ◽  
Cell Responses ◽  
Reference Isolate ◽  
The Impact

Abstract Both natural infection with SARS-CoV-2 and immunization with vaccines induce protective immunity. However, the extent to which such immune responses protect against emerging variants is of increasing importance. Such variants of concern (VOC) include isolates of lineage B.1.1.7, first identified in the UK, and B.1.351, first identified in South Africa. Our data confirm that VOC, particularly those with substitutions at residues 484 and 417, escape neutralization by antibodies directed to the ACE2-binding Class 1 and the adjacent Class 2 epitopes but are susceptible to neutralization by the generally less potent antibodies directed to Class 3 and 4 epitopes on the flanks of the receptor-binding domain. To address the potential threat posed by VOC, we sampled a SARS-CoV-2 uninfected UK cohort recently vaccinated with BNT162b2 (Pfizer-BioNTech, two doses delivered 18-28 days apart), alongside a cohort sampled in the early convalescent stages after natural infection in the first wave of the pandemic in Spring 2020. We tested antibody and T cell responses against a reference isolate of the original circulating lineage, B, and the impact of sequence variation in the B.1.1.7 and B.1.351 VOC. Neutralization of the VOC compared to B isolate was reduced, and this was most evident for the B.1.351 isolate. This reduction in antibody neutralization was less marked in post-boost vaccine-induced responses compared to naturally induced immune responses and could be largely explained by the potency of the homotypic antibody response. After a single vaccination, which induced only modestly neutralizing homotypic antibody titres, neutralization against the VOC was completely abrogated in the majority of vaccinees. Importantly, high magnitude T cell responses were generated after two vaccine doses, with the majority of the T cell response directed against epitopes that are conserved between the prototype isolate B and the VOC. These data indicate that VOC may evade protective neutralizing responses induced by prior infection, and to a lesser extent by immunization, particularly after a single vaccine dose, but the impact of the VOC on T cell responses appears less marked. The results emphasize the need to generate high potency immune responses through vaccination in order to provide protection against these and other emergent variants.

scholarly journals Natural and vaccine-induced antibody and cellular responses against emerging SARS-CoV-2 variants of concern

2021 ◽  
Author(s):  
Donal T. Skelly ◽  
Adam C. Harding ◽  
Javier Gilbert-Jaramillo ◽  
Michael L. Knight ◽  
Stephanie Longet ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Natural Infection ◽  
T Cell Responses ◽  
T Cell Response ◽  
Antibody Neutralization ◽  
Potential Threat ◽  
Cell Responses ◽  
The Uk ◽  
The Impact

Abstract Both natural infection with SARS-CoV-2 and immunization with a number of vaccines induce protective immunity. However, the ability of such immune responses to recognize and therefore protect against emerging variants is a matter of increasing importance. Such variants of concern (VOC) include isolates of lineage B1.1.7, first identified in the UK, and B1.351, first identified in South Africa. Our data confirm that VOC, particularly those with substitutions at residues 484 and 417 escape neutralization by antibodies directed to the ACE2-binding Class 1 and the adjacent Class 2 epitopes but are susceptible to neutralization by the generally less potent antibodies directed to Class 3 and 4 epitopes on the flanks RBD. To address this potential threat, we sampled a SARS-CoV-2 uninfected UK cohort recently vaccinated with BNT162b2 (Pfizer-BioNTech, two doses delivered 18-28 days apart), alongside a cohort naturally infected in the first wave of the epidemic in Spring 2020. We tested antibody and T cell responses against a reference isolate (VIC001) representing the original circulating lineage B and the impact of sequence variation in these two VOCs. We identified a reduction in antibody neutralization against the VOCs which was most evident in the B1.351 variant. However, the majority of the T cell response was directed against epitopes conserved across all three strains. The reduction in antibody neutralization was less marked in post-boost vaccine-induced than in naturally-induced immune responses and could be largely explained by the potency of the homotypic antibody response. However, after a single vaccination, which induced only modestly neutralizing homotypic antibody titres, neutralization against the VOCs was completely abrogated in the majority of vaccinees. These data indicate that VOCs may evade protective neutralising responses induced by prior infection, and to a lesser extent by immunization, particularly after a single vaccine, but the impact of the VOCs on T cell responses appears less marked. The results emphasize the need to generate high potency immune responses through vaccination in order to provide protection against these and other emergent variants. We observed that two doses of vaccine also induced a significant increase in binding antibodies to spike of both SARS-CoV-1 & MERS, in addition to the four common coronaviruses currently circulating in the UK. The impact of antigenic imprinting on the potency of humoral and cellular heterotypic protection generated by the next generation of variant-directed vaccines remains to be determined.

scholarly journals Two doses of SARS-CoV-2 vaccination induce robust immune responses to emerging SARS-CoV-2 variants of concern

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Donal T. Skelly ◽  
Adam C. Harding ◽  
Javier Gilbert-Jaramillo ◽  
Michael L. Knight ◽  
Stephanie Longet ◽  
...  
Keyword(s):  
T Cells ◽  
Single Dose ◽  
T Cell ◽  
Immune Responses ◽  
Natural Infection ◽  
T Cell Response ◽  
High Potency ◽  
Cell Responses ◽  
Reference Isolate ◽  
High Magnitude

AbstractThe extent to which immune responses to natural infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and immunization with vaccines protect against variants of concern (VOC) is of increasing importance. Accordingly, here we analyse antibodies and T cells of a recently vaccinated, UK cohort, alongside those recovering from natural infection in early 2020. We show that neutralization of the VOC compared to a reference isolate of the original circulating lineage, B, is reduced: more profoundly against B.1.351 than for B.1.1.7, and in responses to infection or a single dose of vaccine than to a second dose of vaccine. Importantly, high magnitude T cell responses are generated after two vaccine doses, with the majority of the T cell response directed against epitopes that are conserved between the prototype isolate B and the VOC. Vaccination is required to generate high potency immune responses to protect against these and other emergent variants.

scholarly journals Vaccine-induced immunity provides more robust heterotypic immunity than natural infection to emerging SARS-CoV-2 variants of concern.

2021 ◽  
Author(s):  
Donal T. Skelly ◽  
Adam C. Harding ◽  
Javier Gilbert-Jaramillo ◽  
Michael L. Knight ◽  
Stephanie Longet ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Natural Infection ◽  
T Cell Responses ◽  
T Cell Response ◽  
Antibody Neutralization ◽  
Potential Threat ◽  
Cell Responses ◽  
The Uk ◽  
The Impact

Abstract Both natural infection with SARS-CoV-2 and immunization with a number of vaccines induce protective immunity. However, the ability of such immune responses to recognize and therefore protect against emerging variants is a matter of increasing importance. Such variants of concern (VOC) include isolates of lineage B1.1.7, first identified in the UK, and B1.351, first identified in South Africa. Our data confirm that VOC, particularly those with substitutions at residues 484 and 417 escape neutralization by antibodies directed to the ACE2-binding Class 1 and the adjacent Class 2 epitopes but are susceptible to neutralization by the generally less potent antibodies directed to Class 3 and 4 epitopes on the flanks RBD. To address this potential threat, we sampled a SARS-CoV-2 uninfected UK cohort recently vaccinated with BNT162b2 (Pfizer-BioNTech, two doses delivered 18-28 days apart), alongside a cohort naturally infected in the first wave of the epidemic in Spring 2020. We tested antibody and T cell responses against a reference isolate (VIC001) representing the original circulating lineage B and the impact of sequence variation in these two VOCs. We identified a reduction in antibody neutralization against the VOCs which was most evident in the B1.351 variant. However, the majority of the T cell response was directed against epitopes conserved across all three strains. The reduction in antibody neutralization was less marked in post-boost vaccine-induced than in naturally-induced immune responses and could be largely explained by the potency of the homotypic antibody response. However, after a single vaccination, which induced only modestly neutralizing homotypic antibody titres, neutralization against the VOCs was completely abrogated in the majority of vaccinees. These data indicate that VOCs may evade protective neutralising responses induced by prior infection, and to a lesser extent by immunization, particularly after a single vaccine, but the impact of the VOCs on T cell responses appears less marked. The results emphasize the need to generate high potency immune responses through vaccination in order to provide protection against these and other emergent variants. We observed that two doses of vaccine also induced a significant increase in binding antibodies to spike of both SARS-CoV-1 & MERS, in addition to the four common coronaviruses currently circulating in the UK. The impact of antigenic imprinting on the potency of humoral and cellular heterotypic protection generated by the next generation of variant-directed vaccines remains to be determined.Authorship note: Donal T. Skelly and Adam C. Harding contributed equally; Miles W. Carroll and William S. James contributed equally

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.

Dermatomycoses: Challenges and Human Immune Responses

2014 ◽  
Vol 15 (5) ◽  
pp. 437-444 ◽  
Author(s):  
Muzna Zahur ◽  
Amber Afroz ◽  
Umer Rashid ◽  
Saba Khaliq
Keyword(s):  
Immune Responses ◽  
Human Immune

scholarly journals Pattern of inflammatory immune response determines the clinical course and outcome of COVID-19: unbiased clustering analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eunyoung Emily Lee ◽  
Kyoung-Ho Song ◽  
Woochang Hwang ◽  
Sin Young Ham ◽  
Hyeonju Jeong ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Clustering Analysis ◽  
Validation Cohort ◽  
Inflammatory Responses ◽  
Clinical Course ◽  
Severe Disease ◽  
Outcome Data ◽  
Inflammatory Immune Response ◽  
Cluster 2

AbstractThe objective of the study was to identify distinct patterns in inflammatory immune responses of COVID-19 patients and to investigate their association with clinical course and outcome. Data from hospitalized COVID-19 patients were retrieved from electronic medical record. Supervised k-means clustering of serial C-reactive protein levels (CRP), absolute neutrophil counts (ANC), and absolute lymphocyte counts (ALC) was used to assign immune responses to one of three groups. Then, relationships between patterns of inflammatory responses and clinical course and outcome of COVID-19 were assessed in a discovery and validation cohort. Unbiased clustering analysis grouped 105 patients of a discovery cohort into three distinct clusters. Cluster 1 (hyper-inflammatory immune response) was characterized by high CRP levels, high ANC, and low ALC, whereas Cluster 3 (hypo-inflammatory immune response) was associated with low CRP levels and normal ANC and ALC. Cluster 2 showed an intermediate pattern. All patients in Cluster 1 required oxygen support whilst 61% patients in Cluster 2 and no patient in Cluster 3 required supplementary oxygen. Two (13.3%) patients in Cluster 1 died, whereas no patient in Clusters 2 and 3 died. The results were confirmed in an independent validation cohort of 116 patients. We identified three different patterns of inflammatory immune response to COVID-19. Hyper-inflammatory immune responses with elevated CRP, neutrophilia, and lymphopenia are associated with a severe disease and a worse outcome. Therefore, targeting the hyper-inflammatory response might improve the clinical outcome of COVID-19.

scholarly journals A31 COMPLEX ROLE OF DIETARY FIBERS IN IBD: MICROBES MEDIATE FIBER-INDUCED INFLAMMATION

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 148-150
Author(s):  
H Armstrong ◽  
R Valcheva ◽  
D Santer ◽  
Z Zhang ◽  
A Rieger ◽  
...  
Keyword(s):  
Immune Responses ◽  
Anaerobic Fermentation ◽  
Ex Vivo ◽  
Severe Disease ◽  
Cytokine Secretion ◽  
Dietary Fibers ◽  
Gut Health ◽  
T84 Cells ◽  
Microbial Composition ◽  
Barrier Integrity

Abstract Background Dietary fibers pass through the bowel undigested and are fermented within the intestine by microbes, typically promoting gut health. However, many IBD patients describe experiencing sensitivity to fibers. β-glucan, found on the surface of fungal cells during fungal infection, has been shown to bind to fiber receptors, such as Dectin-1, on host immune cells, resulting in a pro-inflammatory response. These fungal fibres share properties with dietary fibers. Aims As an altered gut microbial composition has been associated with IBD, we hypothesized that the loss of fiber-fermenting microbes populating the gut in IBD could lead to dietary fibers not being efficiently broken down into their beneficial biproducts (e.g. short chain fatty acids; SCFA), resulting in binding of intact fibers to pro-inflammatory host cell receptors. Methods Immune and epithelial cell lines and colonic biopsies cultured ex vivo were incubated with oligofructose or inulin (5g/L), or pre-fermented fibers (24hr anaerobic fermentation). Immune responses were measured by cytokine secretion (ELISA), and expression (qPCR). Barrier integrity was measured by transepithelial resistance (TEER). Food frequency questionnaire (FFQ) data of patient fiber consumption were correlated with gut microbes (shotgun sequencing) and immune responses to fiber in patient biopsies. Results Unfermented oligofructose induced IL-1β secretion in leukocytes (macrophage, T cell, neutrophil) and in colon biopsies from pediatric Crohn disease (CD; n=38) and ulcerative colitis (UC; n=20) patients cultured ex vivo, but not in non-IBD patients (n=21). IL-1β secretion was greater in patients with more severe disease. Pre-fermentation of oligofructose by whole-microbe intestinal washes from non-IBD patients or remission patients reduced secretion of IL-1β, while whole microbe intestinal washes from severe IBD patients were unable to ferment oligofructose or reduce cytokine secretion. Fiber effects on IL-1β secretion in biopsies positively correlated with effects on barrier integrity in T84 cells. Fiber-associated immune responses in patient biopsies cultured ex vivo (ELISA) correlated with fiber avoidance (FFQ) and gut microbiome (sequencing) in matching patient samples. Conclusions Our findings demonstrate that intolerance and avoidance of prebiotic fibers in select IBD patients is associated with the inability to ferment these fibers, leading to pro-inflammatory immune responses and intestinal barrier disruption. This highlights select disease state scenarios, in which administration of fermentable fibers should be avoided and tailored dietary interventions should be considered in IBD patients. Funding Agencies CIHRWeston Foundation

scholarly journals Severely ill COVID-19 patients display impaired exhaustion features in SARS-CoV-2-reactive CD8+ T cells

2021 ◽  
Vol 6 (55) ◽  
pp. eabe4782 ◽  
Author(s):  
Anthony Kusnadi ◽  
Ciro Ramírez-Suástegui ◽  
Vicente Fajardo ◽  
Serena J Chee ◽  
Benjamin J Meckiff ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
Healthy Subjects ◽  
Single Cell Analysis ◽  
Severe Disease ◽  
T Cell Response ◽  
Severe Illness ◽  
Syncytial Virus ◽  
Apoptotic Pathways

The molecular properties of CD8+ T cells that respond to SARS-CoV-2 infection are not fully known. Here, we report on the single-cell transcriptomes of >80,000 virus-reactive CD8+ T cells, obtained using a modified Antigen-Reactive T cell Enrichment (ARTE) assay, from 39 COVID-19 patients and 10 healthy subjects. COVID-19 patients segregated into two groups based on whether the dominant CD8+ T cell response to SARS-CoV-2 was ‘exhausted’ or not. SARS-CoV-2-reactive cells in the exhausted subset were increased in frequency and displayed lesser cytotoxicity and inflammatory features in COVID-19 patients with mild compared to severe illness. In contrast, SARS-CoV-2-reactive cells in the dominant non-exhausted subset from patients with severe disease showed enrichment of transcripts linked to co-stimulation, pro-survival NF-κB signaling, and anti-apoptotic pathways, suggesting the generation of robust CD8+ T cell memory responses in patients with severe COVID-19 illness. CD8+ T cells reactive to influenza and respiratory syncytial virus from healthy subjects displayed polyfunctional features and enhanced glycolysis. Cells with such features were largely absent in SARS-CoV-2-reactive cells from both COVID-19 patients and healthy controls non-exposed to SARS-CoV-2. Overall, our single-cell analysis revealed substantial diversity in the nature of CD8+ T cells responding to SARS-CoV-2.

scholarly journals Immune Restoration Diseases Reflect Diverse Immunopathological Mechanisms

2009 ◽  
Vol 22 (4) ◽  
pp. 651-663 ◽  
Author(s):  
Patricia Price ◽  
David M. Murdoch ◽  
Upasna Agarwal ◽  
Sharon R. Lewin ◽  
Julian H. Elliott ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Cell Activation ◽  
Cell Activation ◽  
De Novo ◽  
Granulomatous Inflammation ◽  
T Cell Response ◽  
Immune Restoration ◽  
Immunological Parameters ◽  
Varicella Zoster

SUMMARY Up to one in four patients infected with human immunodeficiency virus type 1 and given antiretroviral therapy (ART) experiences inflammatory or cellular proliferative disease associated with a preexisting opportunistic infection, which may be subclinical. These immune restoration diseases (IRD) appear to result from the restoration of immunocompetence. IRD associated with intracellular pathogens are characterized by cellular immune responses and/or granulomatous inflammation. Mycobacterial and cryptococcal IRD are attributed to a pathological overproduction of Th1 cytokines. Clinicopathological characteristics of IRD associated with viral infections suggest different pathogenic mechanisms. For example, IRD associated with varicella-zoster virus or JC polyomavirus infection correlate with a CD8 T-cell response in the central nervous system. Exacerbations or de novo presentations of hepatitis associated with hepatitis C virus (HCV) infection following ART may also reflect restoration of pathogen-specific immune responses as titers of HCV-reactive antibodies rise in parallel with liver enzymes and plasma markers of T-cell activation. Correlations between immunological parameters assessed in longitudinal sample sets and clinical presentations are required to illuminate the diverse immunological scenarios described collectively as IRD. Here we present salient clinical features and review progress toward understanding their pathogeneses.

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