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Human Vaccines & Immunotherapeutics Dec 2023The ongoing COVID-19 pandemic highlights that complications and mortality associated with infectious diseases increase with age. Various vaccines are recommended for... (Review)
Review
The ongoing COVID-19 pandemic highlights that complications and mortality associated with infectious diseases increase with age. Various vaccines are recommended for adults, but coverage rates remain suboptimal. Although co-administration would improve vaccine uptake and timely immunization, this is not routine practice in adults. We review key data on co-administration of vaccines in children and adults to reassure healthcare providers about its safety and advantages. In European countries and the United States, combined tetanus, diphtheria, and acellular pertussis boosters as well as meningococcal and human papillomavirus vaccines are recommended for healthy adolescents and adults of certain ages. Vaccination against influenza (annually), pneumococcal disease, and herpes zoster is recommended for older adults and specific risk groups. While co-administration is well established in children, it is less common in adults. Travelers can also receive multiple co-administered vaccines. Pediatric and travel vaccine co-administration has a well-established positive benefit-risk profile and is an efficient and cost-saving strategy to improve coverage. Healthcare providers could more often recommend and practice vaccine co-administration; this would not risk patient safety and health, would improve protection against vaccine-preventable diseases, and would help comply with national vaccination calendars. Recommending bodies may consider revising vaccination schedules to reduce the number of visits.
Topics: Adolescent; Humans; Child; United States; Aged; Vaccination Coverage; Pandemics; COVID-19; Vaccination; Tetanus Toxoid; Diphtheria-Tetanus-acellular Pertussis Vaccines
PubMed: 37039318
DOI: 10.1080/21645515.2023.2195786 -
Cell Host & Microbe Jun 2023Trained immunity is a long-term increase in responsiveness of innate immune cells, induced by certain infections and vaccines. During the last 3 years of the COVID-19... (Review)
Review
Trained immunity is a long-term increase in responsiveness of innate immune cells, induced by certain infections and vaccines. During the last 3 years of the COVID-19 pandemic, vaccines that induce trained immunity, such as BCG, MMR, OPV, and others, have been investigated for their capacity to protect against COVID-19. Further, trained immunity-inducing vaccines have been shown to improve B and T cell responsiveness to both mRNA- and adenovirus-based anti-COVID-19 vaccines. Moreover, SARS-CoV-2 infection itself induces inappropriately strong programs of trained immunity in some individuals, which may contribute to the long-term inflammatory sequelae. In this review, we detail these and other aspects of the role of trained immunity in SARS-CoV-2 infection and COVID-19. We also examine the learnings from the trained immunity studies conducted in the context of this pandemic and discuss how they may help us in preparing for future infectious outbreaks.
Topics: Humans; COVID-19; Pandemics; SARS-CoV-2; Trained Immunity; Viral Vaccines; BCG Vaccine; Immunity, Innate
PubMed: 37321172
DOI: 10.1016/j.chom.2023.05.004 -
BMJ (Clinical Research Ed.) Jun 2023To test for potential non-specific effects of an additional, early measles, mumps, and rubella (MMR) vaccine at age 5-7 months on risk of infection related... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To test for potential non-specific effects of an additional, early measles, mumps, and rubella (MMR) vaccine at age 5-7 months on risk of infection related hospitalisation before age 12 months.
DESIGN
Randomised, double blinded, placebo controlled trial.
SETTING
Denmark, a high income setting with low exposure to MMR.
PARTICIPANTS
6540 Danish infants aged 5 to 7 months.
INTERVENTIONS
Infants were randomly allocated 1:1 to intramuscular injection with standard titre MMR vaccine (M-M-R VaxPro) or placebo (solvent only).
MAIN OUTCOME MEASURES
Hospitalisations for infection, defined as all hospital contacts of infants referred from primary care for hospital evaluation and with an infection diagnosed, analysed as recurrent events, from randomisation to 12 months of age. In secondary analyses implications of censoring for date of subsequent diphtheria, tetanus, pertussis, polio, type B, and immunisation with pneumococci conjugate vaccine (DTaP-IPV-Hib+PCV), potential effect modification by sex, prematurity (<37 weeks' gestation), season, and age at randomisation were tested, and the secondary outcomes of hospitalisations ≥12 hours and antibiotic use were evaluated.
RESULTS
6536 infants were included in the intention-to-treat analysis. 3264 infants randomised to MMR vaccine experienced 786 hospitalisations for infection before age 12 months compared with 762 for the 3272 infants randomised to placebo. In the intention-to-treat analysis the rate of hospitalisations for infection did not differ between the MMR vaccine and placebo groups (hazard ratio 1.03, 95% confidence interval 0.91 to 1.18). For infants randomised to MMR vaccine compared with those randomised to placebo, the hazard ratio of hospitalisations for infection with a duration of at least 12 hours was 1.25 (0.88 to 1.77), and for prescriptions of antibiotics was 1.04 (0.88 to 1.23). No significant effect modifications were found by sex, prematurity, age at randomisation, or season. The estimate did not change when censoring at the date infants received DTaP-IPV-Hib+PCV after randomisation (1.02, 0.90 to 1.16).
CONCLUSION
Findings of this trial conducted in Denmark, a high income setting, do not support the hypothesis that live attenuated MMR vaccine administered early to infants aged 5-7 months decreases the rate of hospitalisations for non-targeted infection before age 12 months.
TRIAL REGISTRATION
EU Clinical Trials Registry EudraCT 2016-001901-18 and ClinicalTrials.gov NCT03780179.
Topics: Infant; Humans; Measles-Mumps-Rubella Vaccine; Mumps; Diphtheria-Tetanus-Pertussis Vaccine; Poliovirus Vaccine, Inactivated; Measles; Immunization; Hospitalization; Haemophilus Vaccines
PubMed: 37286215
DOI: 10.1136/bmj-2022-072724 -
MMWR. Recommendations and Reports :... Sep 2023
THIS REPORT COMPILES AND SUMMARIZES ALL PUBLISHED RECOMMENDATIONS FROM CDC’S ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP) FOR USE OF PNEUMOCOCCAL VACCINES IN ADULTS AGED ≥19 YEARS IN THE UNITED STATES. THIS REPORT ALSO INCLUDES UPDATED AND NEW CLINICAL GUIDANCE FOR IMPLEMENTATION FROM CDC
BEFORE 2021, ACIP RECOMMENDED 23-VALENT PNEUMOCOCCAL POLYSACCHARIDE VACCINE (PPSV23) ALONE (UP TO 2 DOSES), OR BOTH A SINGLE DOSE OF 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE (PCV13) IN COMBINATION WITH 1–3 DOSES OF PPSV23 IN SERIES (PCV13 FOLLOWED BY PPSV23), FOR USE IN U.S. ADULTS DEPENDING ON AGE AND UNDERLYING RISK FOR PNEUMOCOCCAL DISEASE. IN 2021, TWO NEW PNEUMOCOCCAL CONJUGATE VACCINES (PCVS), A 15-VALENT AND A 20-VALENT PCV (PCV15 AND PCV20), WERE LICENSED FOR USE IN U.S. ADULTS AGED ≥18 YEARS BY THE FOOD AND DRUG ADMINISTRATION
ACIP RECOMMENDATIONS SPECIFY THE USE OF EITHER PCV20 ALONE OR PCV15 IN SERIES WITH PPSV23 FOR ALL ADULTS AGED ≥65 YEARS AND FOR ADULTS AGED 19–64 YEARS WITH CERTAIN UNDERLYING MEDICAL CONDITIONS OR OTHER RISK FACTORS WHO HAVE NOT RECEIVED A PCV OR WHOSE VACCINATION HISTORY IS UNKNOWN. IN ADDITION, ACIP RECOMMENDS USE OF EITHER A SINGLE DOSE OF PCV20 OR ≥1 DOSE OF PPSV23 FOR ADULTS WHO HAVE STARTED THEIR PNEUMOCOCCAL VACCINE SERIES WITH PCV13 BUT HAVE NOT RECEIVED ALL RECOMMENDED PPSV23 DOSES. SHARED CLINICAL DECISION-MAKING IS RECOMMENDED REGARDING USE OF A SUPPLEMENTAL PCV20 DOSE FOR ADULTS AGED ≥65 YEARS WHO HAVE COMPLETED THEIR RECOMMENDED VACCINE SERIES WITH BOTH PCV13 AND PPSV23
UPDATED AND NEW CLINICAL GUIDANCE FOR IMPLEMENTATION FROM CDC INCLUDES THE RECOMMENDATION FOR USE OF PCV15 OR PCV20 FOR ADULTS WHO HAVE RECEIVED PPSV23 BUT HAVE NOT RECEIVED ANY PCV DOSE. THE REPORT ALSO INCLUDES CLINICAL GUIDANCE FOR ADULTS WHO HAVE RECEIVED 7-VALENT PCV (PCV7) ONLY AND ADULTS WHO ARE HEMATOPOIETIC STEM CELL TRANSPLANT RECIPIENTS
Topics: Adult; Humans; Advisory Committees; Immunization; Pneumococcal Vaccines; United States; Vaccination; Vaccines, Conjugate
PubMed: 37669242
DOI: 10.15585/mmwr.rr7203a1 -
Current Opinion in Immunology Oct 2023Whooping cough, caused by Bordetella pertussis, is still a major cause of morbidity and mortality worldwide. Current acellular pertussis (aP) vaccines induce potent... (Review)
Review
Whooping cough, caused by Bordetella pertussis, is still a major cause of morbidity and mortality worldwide. Current acellular pertussis (aP) vaccines induce potent circulating IgG and prevent severe disease in children/adults and in infants born to vaccinated mothers. However, they do not prevent nasal infection, allowing asymptomatic transmission of B. pertussis. Studies in animal models have demonstrated that, unlike natural infection, immunization with aP vaccines fails to induce secretory immunoglobulin A (IgA) or interleukin-17 (IL-17)-secreting tissue-resident memory CD4 T (T) cells, required for sustained sterilizing immunity in the nasal mucosa. Live-attenuated vaccines or aP vaccines formulated with novel adjuvants that induce respiratory IgA and T cells, especially when delivered by the nasal route, are in development and have considerable promise as next-generation vaccines against pertussis.
Topics: Child; Animals; Humans; Whooping Cough; Pertussis Vaccine; Bordetella pertussis; Immunization; Immunoglobulin A
PubMed: 37307651
DOI: 10.1016/j.coi.2023.102355 -
Cell Reports May 2023Bacillus Calmette-Guérin (BCG) vaccination is a prototype model for the study of trained immunity (TI) in humans, and results in a more effective response of innate...
Bacillus Calmette-Guérin (BCG) vaccination is a prototype model for the study of trained immunity (TI) in humans, and results in a more effective response of innate immune cells upon stimulation with heterologous stimuli. Here, we investigate the heterogeneity of TI induction by single-cell RNA sequencing of immune cells collected from 156 samples. We observe that both monocytes and CD8 T cells show heterologous transcriptional responses to lipopolysaccharide, with an active crosstalk between these two cell types. Furthermore, the interferon-γ pathway is crucial in BCG-induced TI, and it is upregulated in functional high responders. Data-driven analyses and functional experiments reveal STAT1 to be one of the important transcription factors for TI shared in all identified monocyte subpopulations. Finally, we report the role of type I interferon-related and neutrophil-related TI transcriptional programs in patients with sepsis. These findings provide comprehensive insights into the importance of monocyte heterogeneity during TI in humans.
Topics: Humans; Mycobacterium bovis; BCG Vaccine; Trained Immunity; CD8-Positive T-Lymphocytes; Interferon-gamma; Immunity, Innate
PubMed: 37155329
DOI: 10.1016/j.celrep.2023.112487 -
Frontiers in Immunology 2023Coronavirus disease (Covid-19) has not only shaped awareness of the impact of infectious diseases on global health. It has also provided instructive lessons for better... (Review)
Review
Coronavirus disease (Covid-19) has not only shaped awareness of the impact of infectious diseases on global health. It has also provided instructive lessons for better prevention strategies against new and current infectious diseases of major importance. Tuberculosis (TB) is a major current health threat caused by (Mtb) which has claimed more lives than any other pathogen over the last few centuries. Hence, better intervention measures, notably novel vaccines, are urgently needed to accomplish the goal of the World Health Organization to end TB by 2030. This article describes how the research and development of TB vaccines can benefit from recent developments in the Covid-19 vaccine pipeline from research to clinical development and outlines how the field of TB research can pursue its own approaches. It begins with a brief discussion of major vaccine platforms in general terms followed by a short description of the most widely applied Covid-19 vaccines. Next, different vaccination regimes and particular hurdles for TB vaccine research and development are described. This specifically considers the complex immune mechanisms underlying protection and pathology in TB which involve innate as well as acquired immune mechanisms and strongly depend on fine tuning the response. A brief description of the TB vaccine candidates that have entered clinical trials follows. Finally, it discusses how experiences from Covid-19 vaccine research, development, and rollout can and have been applied to the TB vaccine pipeline, emphasizing similarities and dissimilarities.
Topics: Humans; COVID-19 Vaccines; COVID-19; Tuberculosis; Tuberculosis Vaccines; Communicable Diseases; Vaccine Development
PubMed: 38035095
DOI: 10.3389/fimmu.2023.1273938 -
Frontiers in Immunology 2023Pneumococcal infections continue to pose a significant global health concern, necessitating the development of effective vaccines. Despite the progress shown by... (Review)
Review
Pneumococcal infections continue to pose a significant global health concern, necessitating the development of effective vaccines. Despite the progress shown by pneumococcal polysaccharide and conjugate vaccines, their limited coverage and the emergence of non-vaccine serotypes have highlighted the need for alternative approaches. Protein-based pneumococcal vaccines, targeting conserved surface proteins of , have emerged as a promising strategy. In this review, we provide an overview of the advancements made in the development of pneumococcal protein vaccines. We discuss the key protein vaccine candidates, highlight their vaccination results in animal studies, and explore the challenges and future directions in protein-based pneumococcal vaccine.
Topics: Animals; Pneumococcal Vaccines; Pneumococcal Infections; Streptococcus pneumoniae; Bacterial Proteins; Vaccines, Conjugate
PubMed: 37818378
DOI: 10.3389/fimmu.2023.1278346 -
Frontiers in Immunology 2023Tuberculosis (TB) is a leading cause of morbidity and mortality worldwide. Global research efforts to improve TB control are hindered by insufficient understanding of... (Review)
Review
Tuberculosis (TB) is a leading cause of morbidity and mortality worldwide. Global research efforts to improve TB control are hindered by insufficient understanding of the role that antibodies play in protective immunity and pathogenesis. This impacts knowledge of rational and optimal vaccine design, appropriate diagnostic biomarkers, and development of therapeutics. Traditional approaches for the prevention and diagnosis of TB may be less efficacious in high prevalence, remote, and resource-poor settings. An improved understanding of the immune response to the causative agent of TB, (), will be crucial for developing better vaccines, therapeutics, and diagnostics. While memory CD4+ T cells and cells and cytokine interferon gamma (IFN-g) have been the main identified correlates of protection in TB, mounting evidence suggests that other types of immunity may also have important roles. TB serology has identified antibodies and functional characteristics that may help diagnose infection and distinguish between different TB disease states. To date, no serological tests meet the World Health Organization (WHO) requirements for TB diagnosis, but multiplex assays show promise for improving the sensitivity and specificity of TB serodiagnosis. Monoclonal antibody (mAb) therapies and serum passive infusion studies in murine models of TB have also demonstrated some protective outcomes. However, animal models that better reflect the human immune response to are necessary to fully assess the clinical utility of antibody-based TB prophylactics and therapeutics. Candidate TB vaccines are not designed to elicit an -specific antibody response, but evidence suggests BCG and novel TB vaccines may induce protective antibodies. The potential of the humoral immune response in TB monitoring and control is being investigated and these studies provide important insight into the functional role of antibody-mediated immunity against TB. In this review, we describe the current state of development of antibody-based clinical tools for TB, with a focus on diagnostic, therapeutic, and vaccine-based applications.
Topics: Humans; Animals; Mice; Tuberculosis; Mycobacterium tuberculosis; Tuberculosis Vaccines; Cytokines; Interferon-gamma; Antibodies
PubMed: 38162666
DOI: 10.3389/fimmu.2023.1278947 -
Immunity Jan 2024Immune responses are tightly regulated yet highly variable between individuals. To investigate human population variation of trained immunity, we immunized healthy...
Immune responses are tightly regulated yet highly variable between individuals. To investigate human population variation of trained immunity, we immunized healthy individuals with Bacillus Calmette-Guérin (BCG). This live-attenuated vaccine induces not only an adaptive immune response against tuberculosis but also triggers innate immune activation and memory that are indicative of trained immunity. We established personal immune profiles and chromatin accessibility maps over a 90-day time course of BCG vaccination in 323 individuals. Our analysis uncovered genetic and epigenetic predictors of baseline immunity and immune response. BCG vaccination enhanced the innate immune response specifically in individuals with a dormant immune state at baseline, rather than providing a general boost of innate immunity. This study advances our understanding of BCG's heterologous immune-stimulatory effects and trained immunity in humans. Furthermore, it highlights the value of epigenetic cell states for connecting immune function with genotype and the environment.
Topics: Humans; BCG Vaccine; Trained Immunity; Multiomics; Vaccination; Epigenesis, Genetic
PubMed: 38198850
DOI: 10.1016/j.immuni.2023.12.005