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Cell Jul 2022Cancer vaccines aim to direct the immune system to eradicate cancer cells. Here we review the essential immunologic concepts underpinning natural immunity and highlight... (Review)
Review
Cancer vaccines aim to direct the immune system to eradicate cancer cells. Here we review the essential immunologic concepts underpinning natural immunity and highlight the multiple unique challenges faced by vaccines targeting cancer. Recent technological advances in mass spectrometry, neoantigen prediction, genetically and pharmacologically engineered mouse models, and single-cell omics have revealed new biology, which can help to bridge this divide. We particularly focus on translationally relevant aspects, such as antigen selection and delivery and the monitoring of human post-vaccination responses, and encourage more aggressive exploration of novel approaches.
Topics: Animals; Cancer Vaccines; Humans; Immune System; Immunity, Innate; Mice; Neoplasms; Vaccination; Vaccines
PubMed: 35835100
DOI: 10.1016/j.cell.2022.06.035 -
Frontiers in Immunology 2022Since the onset of the COVID-19 pandemic, the medical field has been forced to apply the basic knowledge of immunology with the most up-to-date SARS-CoV-2 findings and... (Review)
Review
Since the onset of the COVID-19 pandemic, the medical field has been forced to apply the basic knowledge of immunology with the most up-to-date SARS-CoV-2 findings and translate it to the population of the whole world in record time. Following the infection with the viral antigen, adaptive immune responses are activated mainly by viral particle encounters with the antigen-presenting cells or B cell receptors, which induce further biological interactions to defend the host against the virus. After the infection has been warded off, the immunological memory is developed. The SARS-CoV cellular immunity has been shown to persist even 17 years after the infection, despite the undetectable humoral component. Similar has been demonstrated for the SARS-CoV-2 T cell memory in a shorter period by assessing interferon-gamma levels when heparinized blood is stimulated with the virus-specific peptides. T cells also play an irreplaceable part in a humoral immune reaction as the backbone of a cellular immune response. They both provide the signals for B cell activation and the maturation, competence, and memory of the humoral response. B cell production of IgA was shown to be of significant influence in mediating mucosal immunity as the first part of the defense mechanism and in the development of nasal vaccines. Here, we interpret the recent SARS-CoV-2 available research, which encompasses the significance and the current understanding of adaptive immune activity, and compare it among naive, exposed, and vaccinated blood donors. Our recent data showed that those who recovered from COVID-19 and those who are vaccinated with EMA-approved vaccines had a long-lasting cellular immunity. Additionally, we analyze the humoral responses in immunocompromised patients and memory mediated by cellular immunity and the impact of clonality in the SARS-CoV-2 pandemic regarding breakthrough infections and variants of concern, both B.1.617.2 (Delta) and B.1.1.529 (Omicron) variants.
Topics: COVID-19; COVID-19 Vaccines; Humans; Immunity, Humoral; Pandemics; SARS-CoV-2; Vaccination
PubMed: 35603211
DOI: 10.3389/fimmu.2022.848582 -
Current Opinion in Immunology Aug 2022The concept that only adaptive immunity can build immunological memory has been challenged in the past decade. Live attenuated vaccines such as the Bacillus... (Review)
Review
The concept that only adaptive immunity can build immunological memory has been challenged in the past decade. Live attenuated vaccines such as the Bacillus Calmette-Guérin, measles-containing vaccines, and the oral polio vaccine have been shown to reduce overall mortality beyond their effects attributable to the targeted diseases. After an encounter with a primary stimulus, epigenetic and metabolic reprogramming of bone marrow progenitor cells and functional changes of tissue immune cell populations result in augmented immune responses against a secondary challenge. This process has been termed trained immunity. This review describes the mechanisms leading to trained immunity and summarizes the most important developments from the past few years.
Topics: Adaptive Immunity; BCG Vaccine; Humans; Immunity, Innate; Immunologic Memory; Mycobacterium bovis; Vaccination
PubMed: 35597182
DOI: 10.1016/j.coi.2022.102190 -
Cell Host & Microbe May 2022The maternal immune system protects developing offspring against pathogens before birth via transplacental transfer and after birth through secreted milk. This... (Review)
Review
The maternal immune system protects developing offspring against pathogens before birth via transplacental transfer and after birth through secreted milk. This transferred maternal immunity influences each generation's susceptibility to infections and responsiveness to immunization. Thus, boosting immunity in the maternal-neonatal dyad is a potentially valuable public health strategy. Additionally, at critical times during fetal and postnatal development, environmental factors and immune stimuli influence immune development. These "windows of opportunity" offer a chance to identify both risk and protective factors that promote long-term health and limit disease. Here, we review pre- and postpartum maternal immune factors that protect against infectious agents in offspring and how they may shape the infant's immune landscape over time. Additionally, we discuss the influence of maternal immunity on the responsiveness to immunization in early life. Lastly, when maternal factors are insufficient to prevent neonatal infectious diseases, we discuss pre- and postnatal therapeutic strategies for the maternal-neonatal dyad.
Topics: Animals; Communicable Diseases; Female; Humans; Immunity, Maternally-Acquired; Immunization; Immunologic Factors; Infant; Infant, Newborn; Milk; Vaccination
PubMed: 35550669
DOI: 10.1016/j.chom.2022.04.007 -
Immunity May 2022The lungs are constantly exposed to inhaled debris, allergens, pollutants, commensal or pathogenic microorganisms, and respiratory viruses. As a result, innate and... (Review)
Review
The lungs are constantly exposed to inhaled debris, allergens, pollutants, commensal or pathogenic microorganisms, and respiratory viruses. As a result, innate and adaptive immune responses in the respiratory tract are tightly regulated and are in continual flux between states of enhanced pathogen clearance, immune-modulation, and tissue repair. New single-cell-sequencing techniques are expanding our knowledge of airway cellular complexity and the nuanced connections between structural and immune cell compartments. Understanding these varied interactions is critical in treatment of human pulmonary disease and infections and in next-generation vaccine design. Here, we review the innate and adaptive immune responses in the lung and airways following infection and vaccination, with particular focus on influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The ongoing SARS-CoV-2 pandemic has put pulmonary research firmly into the global spotlight, challenging previously held notions of respiratory immunity and helping identify new populations at high risk for respiratory distress.
Topics: COVID-19; Humans; Immunity, Innate; Immunity, Mucosal; Lung; SARS-CoV-2; Vaccination
PubMed: 35545027
DOI: 10.1016/j.immuni.2022.04.013 -
Nature Immunology Dec 2022Aside from centrally induced trained immunity in the bone marrow (BM) and peripheral blood by parenteral vaccination or infection, evidence indicates that...
Aside from centrally induced trained immunity in the bone marrow (BM) and peripheral blood by parenteral vaccination or infection, evidence indicates that mucosal-resident innate immune memory can develop via a local inflammatory pathway following mucosal exposure. However, whether mucosal-resident innate memory results from integrating distally generated immunological signals following parenteral vaccination/infection is unclear. Here we show that subcutaneous Bacillus Calmette-Guérin (BCG) vaccination can induce memory alveolar macrophages (AMs) and trained immunity in the lung. Although parenteral BCG vaccination trains BM progenitors and circulating monocytes, induction of memory AMs is independent of circulating monocytes. Rather, parenteral BCG vaccination, via mycobacterial dissemination, causes a time-dependent alteration in the intestinal microbiome, barrier function and microbial metabolites, and subsequent changes in circulating and lung metabolites, leading to the induction of memory macrophages and trained immunity in the lung. These data identify an intestinal microbiota-mediated pathway for innate immune memory development at distal mucosal tissues and have implications for the development of next-generation vaccine strategies against respiratory pathogens.
Topics: BCG Vaccine; Macrophages, Alveolar; Trained Immunity; Lung; Vaccination; Immunity, Innate
PubMed: 36456739
DOI: 10.1038/s41590-022-01354-4 -
BMJ Global Health May 2021Global gains in vaccination coverage during the early 21st century have been threatened by the emergence of antivaccination groups that have questioned the effectiveness... (Review)
Review
Global gains in vaccination coverage during the early 21st century have been threatened by the emergence of antivaccination groups that have questioned the effectiveness of vaccines to generate public distrust of vaccines and immunisation programmes. This manuscript summarises six key topics that have been at the centre of global discussions on vaccine safety during the early 21st century: thiomersal in multi-dose non-live vaccines, aluminium adjuvants used with several non-live vaccines, autism and auto-immune conditions as possible consequences of vaccination, a risk of immune overload with increasing numbers of vaccinations, and detrimental non-specific effects (NSEs) of vaccination. For each topic, we describe the hypothesis behind the public concern, the evidence reviewed by the WHO's Global Advisory Committee for Vaccine Safety (GACVS) during 1999-2019, and any significant new data that has emerged since GACVS conclusions were made. Although the scientific evidence on these issues overwhelmingly supports the safety of vaccines, communication messages to caregivers and providers need to condense and convey scientific information in an appropriate way to address concerns contributing to vaccine distrust. In addition, there is need for further studies specifically designed to address both positive and negative NSE of vaccination. The role of GACVS will be increasingly important in evaluating the evidence and engaging the global community in promoting and assuring the safety of vaccines in the decades to come as we move into an era in which we use new vaccination platforms, antigens and formulations.
Topics: Advisory Committees; Altruism; Communication; Humans; Vaccination; Vaccines
PubMed: 34011504
DOI: 10.1136/bmjgh-2020-004898 -
Current Biology : CB Feb 2021Herd immunity is an important yet often misunderstood concept in epidemiology. As immunity accumulates in a population - naturally during the course of an epidemic or...
Herd immunity is an important yet often misunderstood concept in epidemiology. As immunity accumulates in a population - naturally during the course of an epidemic or through vaccination - the spread of an infectious disease is limited by the depletion of susceptible hosts. If a sufficient proportion of the population is immune - above the 'herd immunity threshold' - then transmission generally cannot be sustained. Maintaining herd immunity is therefore critical to long-term disease control. In this primer, we discuss the concept of herd immunity from first principles, clarify common misconceptions, and consider the implications for disease control.
Topics: Animals; Communicable Disease Control; Epidemics; Humans; Immunity, Herd; Mice; Vaccination
PubMed: 33621500
DOI: 10.1016/j.cub.2021.01.006 -
Nature Reviews. Immunology Jan 2022The need for highly effective vaccines that induce robust and long-lasting immunity has never been more apparent. However, for reasons that are still poorly understood,... (Review)
Review
The need for highly effective vaccines that induce robust and long-lasting immunity has never been more apparent. However, for reasons that are still poorly understood, immune responses to vaccination are highly variable between different individuals and different populations. Furthermore, vaccine immunogenicity is frequently suboptimal in the very populations who are at most risk from infectious disease, including infants, the elderly, and those living in low-income and middle-income countries. Although many factors have the potential to influence vaccine immunogenicity and therefore vaccine effectiveness, increasing evidence from clinical studies and animal models now suggests that the composition and function of the gut microbiota are crucial factors modulating immune responses to vaccination. In this Review, we synthesize this evidence, discuss the immunological mechanisms that potentially mediate these effects and consider the potential of microbiota-targeted interventions to optimize vaccine effectiveness.
Topics: Animals; Gastrointestinal Microbiome; Immunity; Microbiota; Vaccination; Vaccines
PubMed: 34002068
DOI: 10.1038/s41577-021-00554-7 -
Frontiers in Immunology 2020Over the last years, an increasing number of outbreaks of vaccine-preventable infectious diseases has been reported. Besides elderly and immunocompromised individuals,... (Review)
Review
Over the last years, an increasing number of outbreaks of vaccine-preventable infectious diseases has been reported. Besides elderly and immunocompromised individuals, newborns and small infants are most susceptible to infections, as their immune system is still immature. This vulnerability during infancy can be mitigated by the transplacental transfer of pathogen-specific antibodies and other mediators of immunity from mother to the fetus during pregnancy, followed postnatally by breast milk-derived immunity. Since this largely antibody-mediated passive immunity can prevent the newborn from infections, neonatal immunity depends strongly on the maternal concentration of respective specific antibodies during pregnancy. If titers are low or wane rapidly after birth, the protection transferred to the child may not be sufficient to prevent disease. Moreover, emerging concepts propose that mothers may transfer active immunity to the newborns via vertical transfer of pathogen-specific T cells. Overall, a promising strategy to augment and prolong neonatal immunity is to vaccinate the mother before or during pregnancy in order to boost maternal antibody concentrations or availability of specific T cells. Hence, a large number of pre-and postconceptional vaccine trials have been carried out to test and confirm this concept. We here highlight novel insights arising from recent research endeavors on the influence of prenatal maternal vaccination against pathogens that can pose a threat for newborns, such as measles, pertussis, rubella and influenza A. We delineate pathways involved in the transfer of specific maternal antibodies. We also discuss the consequences for children's health and long-term immunity resulting from an adjustment of prenatal vaccination regimes.
Topics: Female; Humans; Immunity, Maternally-Acquired; Infant, Newborn; Male; Pregnancy; Vaccination
PubMed: 32296443
DOI: 10.3389/fimmu.2020.00555