scholarly journals Vaccine-Induced Cellular Immunity against Bordetella pertussis: Harnessing Lessons from Animal and Human Studies to Improve Design and Testing of Novel Pertussis Vaccines

Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 877
Author(s):  
Anja Saso ◽  
Beate Kampmann ◽  
Sophie Roetynck
Keyword(s):  
Whooping Cough ◽  
Vaccine Coverage ◽  
Current Knowledge ◽  
Herd Immunity ◽  
Cell Mediated Immunity ◽  
Improve Design ◽  
Vaccine Preventable Diseases ◽  
Key Factor ◽  
Cellular Immune ◽  
Design And Testing

Pertussis (‘whooping cough’) is a severe respiratory tract infection that primarily affects young children and unimmunised infants. Despite widespread vaccine coverage, it remains one of the least well-controlled vaccine-preventable diseases, with a recent resurgence even in highly vaccinated populations. Although the exact underlying reasons are still not clear, emerging evidence suggests that a key factor is the replacement of the whole-cell (wP) by the acellular pertussis (aP) vaccine, which is less reactogenic but may induce suboptimal and waning immunity. Differences between vaccines are hypothesised to be cell-mediated, with polarisation of Th1/Th2/Th17 responses determined by the composition of the pertussis vaccine given in infancy. Moreover, aP vaccines elicit strong antibody responses but fail to protect against nasal colonisation and/or transmission, in animal models, thereby potentially leading to inadequate herd immunity. Our review summarises current knowledge on vaccine-induced cellular immune responses, based on mucosal and systemic data collected within experimental animal and human vaccine studies. In addition, we describe key factors that may influence cell-mediated immunity and how antigen-specific responses are measured quantitatively and qualitatively, at both cellular and molecular levels. Finally, we discuss how we can harness this emerging knowledge and novel tools to inform the design and testing of the next generation of improved infant pertussis vaccines.

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 Getting personal: how vaccination exemptions shape herd immunity

2018 ◽  
Author(s):  
Emma R Nedell ◽  
Romain Garnier ◽  
Saad B Omer ◽  
Shweta Bansal
Keyword(s):  
Policy Change ◽  
Spatial Clustering ◽  
Vaccine Coverage ◽  
Herd Immunity ◽  
The United States ◽  
Vaccine Preventable Diseases ◽  
Vaccination Rates ◽  
Before And After ◽  
Exemption Policy ◽  
Epidemiological Effects

Background: State-mandated school entry immunization requirements in the United States play an important role in achieving high vaccine coverage and preventing outbreaks of vaccine-preventable diseases. Most states allow non-medical exemptions that let children remain unvaccinated on the basis of personal beliefs. However, the ease of obtaining such exemptions varies, resulting in a patchwork of state vaccination exemption laws, contributing to heterogeneity in vaccine coverage across the country. In this study, we evaluate epidemiological effects and spatial variations in non-medical exemption rates in the context of vaccine policies. Methods and Findings: We first analyzed the correlation between non-medical exemption rates and vaccine coverage for three significant childhood vaccinations and found that higher rates of non-medical exemptions were associated with lower vaccination rates of school-aged children in all cases. We then identified a subset of states where exemption policy has recently changed and found that the effects on statewide non-medical exemption rates varied widely. Focusing further on Vermont and California, we illustrated how the decrease in non-medical exemptions due to policy change was concurrent to an increase in medical exemptions (in CA) or religious exemptions (in VT). Finally, a spatial clustering analysis was performed for Connecticut, Illinois, and California, identifying clusters of high non-medical exemption rates in these states before and after a policy change occurred. The clustering analyses show that policy changes affect spatial distribution of non-medical exemptions within a state. Conclusions: Our work suggests that vaccination policies have significant impacts on patterns of herd immunity. Our findings can be used to develop evidence-based vaccine legislation.

Pertussis

2018 ◽  
Keyword(s):  
Public Health ◽  
Disease Ecology ◽  
Evolutionary Biology ◽  
Expert Knowledge ◽  
Whooping Cough ◽  
Vaccine Coverage ◽  
The United States ◽  
Vaccine Preventable Diseases ◽  
Treatment And Prevention ◽  
Evolutionary Epidemiology

Pertussis, or whooping cough, is a respiratory disease caused primarily by infection with the bacterium Bordetella pertussis. It remains one of the leading causes of death among vaccine-preventable diseases worldwide and recent years have seen its alarming re-emergence in many regions (including the United States and much of Europe), despite sustained high levels of vaccine coverage. The causes of the resurgence remain contentious, in part due to inherent complexities of the pathogen’s biology, in part due to pronounced variation in the treatment and prevention strategies between different countries and regions, and in part due to long-standing disagreement among scientific researchers studying pertussis. This edited volume brings together expert knowledge from disparate fields with the overall aim of synthesizing the current understanding of this critically important, global pathogen. Pertussis: Epidemiology, Immunology, and Evolution is an advanced text suitable for graduate-level students taking courses in evolutionary epidemiology, disease ecology, and evolutionary biology, as well as academics, public health officials, and researchers in these fields. It also offers a very useful introduction to a wider audience of public health practitioners, microbiologists, epidemiologists, medical professionals, and vaccine biologists

scholarly journals Improved Temporal Trends of Vaccination Coverage Rates in Childhood after the Mandatory Vaccination Act, Italy 2014–2019

2021 ◽  
Vol 10 (12) ◽  
pp. 2540
Author(s):  
Michela Sabbatucci ◽  
Anna Odone ◽  
Carlo Signorelli ◽  
Andrea Siddu ◽  
Francesco Maraglino ◽  
...  
Keyword(s):  
Vaccine Coverage ◽  
Temporal Trends ◽  
Herd Immunity ◽  
Haemophilus Influenzae Type ◽  
Childhood Immunization ◽  
Vaccine Preventable Diseases ◽  
Immunization Rates ◽  
Health Strategy ◽  
Coverage Rates ◽  
The Impact

Maintaining high vaccine coverage (VC) for pediatric vaccinations is crucial to ensure herd immunity, reducing the risk of vaccine-preventable diseases (VPD). The Italian vaccination Law (n. 119/2017) reinforced mandates for polio, diphtheria, tetanus, and hepatitis B, extending the mandate to pertussis, Haemophilus influenzae type b, chickenpox, measles, mumps, and rubella, for children up to 16 years of age. We analyzed the national temporal trends of childhood immunization rates from 2014 to 2019 to evaluate the impact of the mandatory reinforcement law set in 2017 as a sustainable public health strategy in Italy. In a 3-year period, 9 of the 10 compulsory vaccinations reached the threshold of 95% and VC for chicken pox increased up to 90.5%, significantly. During the same period, the recommended vaccinations (against meningococcus B and C, pneumococcus, and rotavirus) also recorded a significant increase in VC trends. In conclusion, although the reinforcement of compulsory vaccination generated a wide public debate that was amplified by traditional and social media, the 3-year evaluation highlights positive results.

scholarly journals Childhood vaccination as a part of the National Immunization Schedule during the COVID-19: problems and potential solutions

2021 ◽  
Vol 4 (1) ◽  
pp. 85-89
Author(s):  
A.A. Girina ◽  
◽  
A.L. Zaplatnikov ◽  
F.I. Petrovskiy ◽  
L.P. Tandalova ◽  
...  
Keyword(s):  
Whooping Cough ◽  
Herd Immunity ◽  
Childhood Vaccination ◽  
Immunization Schedule ◽  
Vaccine Preventable Diseases ◽  
National Immunization ◽  
Fold Reduction ◽  
High Level ◽  
In The Beginning ◽  
And Child Health

Aim: to compare monthly implementation of immunization plan as a part of the National Immunization Schedule in 2019 and 2020 in children aged 0–18 years. Patients and Methods: monthly and annual form No. 5 “Information on prophylactic immunization” (from January 2019 to December 2020) was analyzed. Monthly implementation of immunization plan for each vaccine-preventable disease (whooping cough, poliomyelitis, mumps, rubella, measles, diphtheria tetanus and other) were analyzed separately. Results: in the beginning of the COVID-19 pandemic, a significant (8.8-fold) reduction in the coverage of children with immunization against vaccine-preventable diseases was reported compared to 2019 (р<0.0001). The reduction in the implementation of immunization schedule required urgent solutions to maintain a high level of herd immunity. The recovery of the required implementation of immunization plan against whooping cough and poliomyelitis was achieved by the end of 2020. The recovery of the required implementation of immunization plan against diphtheria and tetanus, measles, rubella, and mumps will be achieved in September 2020 (considering the National Immunization Schedule that includes revaccinations in preschool and school years). Conclusions: timely identification of the drawbacks of the organization of immunization and the prompt development of effective measures and implementation into clinical practice allowed for full implementation of immunization plan in children in 2020, despite the ongoing COVID-19 pandemic. KEYWORDS: vaccination, children, National Immunization Schedule, revaccination, COVID-19 pandemic. FOR CITATION: Girina A.A., Zaplatnikov A.L., Petrovskiy F.I., Tandalova L.P. Childhood vaccination as a part of the National Immunization Schedule during the COVID-19: problems and potential solutions. Russian Journal of Woman and Child Health. 2021;4(1):85–89. DOI: 10.32364/2618-8430-2021-4-1-85-89.

Spatial Clustering of Vaccine Exemptions on the Risk of a Measles Outbreak

PEDIATRICS ◽  
2021 ◽  
Vol 149 (1) ◽  
Author(s):  
Ashley Gromis ◽  
Ka-Yuet Liu
Keyword(s):  
Large Scale ◽  
Spatial Clustering ◽  
Vaccine Coverage ◽  
Herd Immunity ◽  
The United States ◽  
Vaccine Preventable Diseases ◽  
Measles Outbreak ◽  
Measles Outbreaks ◽  
Lower Population ◽  
Local Herd

OBJECTIVES Areas of increased school-entry vaccination exemptions play a key role in epidemics of vaccine-preventable diseases in the United States. California eliminated nonmedical exemptions in 2016, which increased overall vaccine coverage but also rates of medical exemptions. We examine how spatial clustering of exemptions contributed to measles outbreak potential pre- and postpolicy change. METHODS We modeled measles transmission in an empirically calibrated hypothetical population of youth aged 0 to 17 years in California and compared outbreak sizes under the observed spatial clustering of exemptions in schools pre- and postpolicy change with counterfactual scenarios of no postpolicy change increase in medical exemptions, no clustering of exemptions, and lower population immunization levels. RESULTS The elimination of nonmedical exemptions significantly reduced both average and maximal outbreak sizes, although increases in medical exemptions resulted in more than twice as many infections, on average, than if medical exemptions were maintained at prepolicy change levels. Spatial clustering of nonmedical exemptions provided some initial protection against random introduction of measles infections; however, it ultimately allowed outbreaks with thousands more infections than when exemptions were randomly distributed. The large-scale outbreaks produced by exemption clusters could not be reproduced when exemptions were distributed randomly until population vaccination was lowered by &gt;6 percentage points. CONCLUSIONS Despite the high overall vaccinate rate, the spatial clustering of exemptions in schools was sufficient to threaten local herd immunity and reduce protection from measles outbreaks. Policies strengthening vaccine requirements may be less effective if alternative forms of exemptions (eg, medical) are concentrated in existing low-immunization areas.

scholarly journals Dose Response of Attenuated Bordetella pertussis BPZE1-Induced Protection in Mice

2010 ◽  
Vol 17 (3) ◽  
pp. 317-324 ◽  
Author(s):  
Nathalie Mielcarek ◽  
Anne-Sophie Debrie ◽  
Severine Mahieux ◽  
Camille Locht
Keyword(s):  
Bordetella Pertussis ◽  
Whooping Cough ◽  
Vaccine Coverage ◽  
Mouse Lung ◽  
High Dose ◽  
Cell Mediated Immunity ◽  
Lung Colonization ◽  
Current Vaccine ◽  
Two Parameters ◽  
Dose Dependent

ABSTRACT Despite the availability of efficacious vaccines, the incidence of whooping cough is still high in many countries and is even increasing in countries with high vaccine coverage. Most severe and life-threatening pertussis cases occur in infants who are too young to be sufficiently protected by current vaccine regimens. As a potential solution to this problem, we have developed an attenuated live Bordetella pertussis vaccine strain, named BPZE1. Here, we show that after a single administration, BPZE1 induces dose-dependent protection against challenge with virulent B. pertussis in low-dose and in high-dose intranasal mouse lung colonization models. In addition, we observed BPZE1 dose-dependent antibody titers to B. pertussis antigens, as well as cell-mediated immunity, evidenced by the amounts of gamma interferon (IFN-γ) released from spleen cells upon stimulation with B. pertussis antigens. These two parameters may perhaps be used as readouts in clinical trials in humans that are currently being planned.

scholarly journals Treatment with anti-FasL antibody preserves memory lymphocytes and virus-specific cellular immunity in macaques challenged with simian immunodeficiency virus

Blood ◽  
2009 ◽  
Vol 114 (6) ◽  
pp. 1196-1204 ◽  
Author(s):  
Bhawna Poonia ◽  
Maria S. Salvato ◽  
Hideo Yagita ◽  
Toshihiro Maeda ◽  
Ko Okumura ◽  
...  
Keyword(s):  
Immune Responses ◽  
Rhesus Macaques ◽  
Cell Mediated Immunity ◽  
Human Beings ◽  
Cd8 Cells ◽  
Immunodeficiency Virus ◽  
Key Factor ◽  
Siv Infection ◽  
Vesicular Stomatitis ◽  
Cellular Immune

AbstractImmune deficiency viruses such as SIV in macaques or HIV-1 in human beings have evolved mechanisms to defeat host immunity that also impact the efficacy of vaccines. A key factor for vaccine protection is whether immune responses elicited by prior immunization remain at levels sufficient to limit disease progression once a host is exposed to the pathogen. One potential mechanism for escaping pre-existing immunity is to trigger death among antigen-activated cells. We tested whether FasL/CD178 is involved in destroying preexisting immunity. Rhesus macaques were immunized with recombinant vesicular stomatitis virus vaccine expressing SIV Gag to elicit cellular immune responses, then treated with antibody that neutralizes FasL and challenged with intravenous SIVmac251. Compared with animals injected with control antibody, anti-FasL–treated macaques had superior preservation of central memory CD4+ and CD8+ cells and decreased regulatory T cells in the blood. The CD4+ and CD8+ lymphocytes from treated animals responded better to SIV Gag compared with controls, evidenced by higher cell-mediated immune responses to viral antigens for at least 17 weeks after SIV challenge. Anti-FasL treatment during the initial stages of acute SIV infection preserved the T-cell compartment and sustained cell-mediated immunity to SIV.

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 Bone morphogenetic proteins, breast cancer, and bone metastases: striking the right balance

2017 ◽  
Vol 24 (10) ◽  
pp. R349-R366 ◽  
Author(s):  
Catherine Zabkiewicz ◽  
Jeyna Resaul ◽  
Rachel Hargest ◽  
Wen Guo Jiang ◽  
Lin Ye
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Bone Morphogenetic Proteins ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Breast Tumour ◽  
Cellular Functions ◽  
Foetal Development ◽  
Key Factor ◽  
The Right

Bone morphogenetic proteins (BMPs) belong to the TGF-β super family, and are essential for the regulation of foetal development, tissue differentiation and homeostasis and a multitude of cellular functions. Naturally, this has led to the exploration of aberrance in this highly regulated system as a key factor in tumourigenesis. Originally identified for their role in osteogenesis and bone turnover, attention has been turned to the potential role of BMPs in tumour metastases to, and progression within, the bone niche. This is particularly pertinent to breast cancer, which commonly metastasises to bone, and in which studies have revealed aberrations of both BMP expression and signalling, which correlate clinically with breast cancer progression. Ultimately a BMP profile could provide new prognostic disease markers. As the evidence suggests a role for BMPs in regulating breast tumour cellular function, in particular interactions with tumour stroma and the bone metastatic microenvironment, there may be novel therapeutic potential in targeting BMP signalling in breast cancer. This review provides an update on the current knowledge of BMP abnormalities and their implication in the development and progression of breast cancer, particularly in the disease-specific bone metastasis.

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