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Nature Communications May 2024Bone marrow plasma cells (BMPC) are the correlate of humoral immunity, consistently releasing antibodies into the bloodstream. It remains unclear if BMPC reflect...
Bone marrow plasma cells (BMPC) are the correlate of humoral immunity, consistently releasing antibodies into the bloodstream. It remains unclear if BMPC reflect different activation environments or maturation of their precursors. Here we define human BMPC heterogeneity and track the recruitment of antibody-secreting cells (ASC) from SARS-CoV-2 vaccine immune reactions to the bone marrow (BM). Trajectories based on single-cell transcriptomes and repertoires of peripheral and BM ASC reveal sequential colonisation of BMPC compartments. In activated B cells, IL-21 suppresses CD19 expression, indicating that CD19-BMPC are derived from follicular, while CD19-BMPC originate from extrafollicular immune reactions. In primary immune reactions, both CD19- and CD19-BMPC compartments are populated. In secondary immune reactions, most BMPC are recruited to CD19-BMPC compartments, reflecting their origin from extrafollicular reactivations of memory B cells. A pattern also observable in vaccinated-convalescent individuals and upon diphtheria/tetanus/pertussis recall-vaccination. Thus, BMPC diversity reflects the evolution of a given humoral immune response.
Topics: Humans; Plasma Cells; Interleukins; Bone Marrow; Antigens, CD19; Immunity, Humoral; COVID-19; SARS-CoV-2; Bone Marrow Cells; Single-Cell Analysis; Adult; B-Lymphocytes; Antibody-Producing Cells; Female; Male; Vaccination; Middle Aged; Diphtheria-Tetanus-Pertussis Vaccine
PubMed: 38755157
DOI: 10.1038/s41467-024-48570-0 -
Clinical and Experimental Vaccine... Apr 2024Pertussis bacteria have many pathogenic and virulent antigens and severe adverse reactions have occurred when using inactivated whole-cell pertussis vaccines. Therefore,...
PURPOSE
Pertussis bacteria have many pathogenic and virulent antigens and severe adverse reactions have occurred when using inactivated whole-cell pertussis vaccines. Therefore, inactivated acellular pertussis (aP) vaccines and genetically detoxified recombinant pertussis (rP) vaccines are being developed. The aim of this study was to assess the safety profile of a novel rP vaccine under development in comparison to commercial diphtheria-tetanus-acellular pertussis (DTaP) vaccines.
MATERIALS AND METHODS
The two positive control DTaP vaccines (two- and tri-components aP vaccines) and two experimental recombinant DTaP (rDTaP) vaccine (two- and tri-components aP vaccines adsorbed to either aluminum hydroxide or purified oat beta-glucan) were used. Temperature histamine sensitization test (HIST), indirect Chinese hamster ovary (CHO) cell cluster assay, mouse-weight-gain (MWG) test, leukocytosis promoting (LP) test, and intramuscular inflammatory cytokine assay of the injection site performed for safety assessments.
RESULTS
HIST results showed absence of residual pertussis toxin (PTx) in both control and experimental DTaP vaccine groups, whereas in groups immunized with tri-components vaccines, the experimental tri-components rDTaP absorbed to alum showed an ultra-small amount of 0.0066 IU/mL. CHO cell clustering was observed from 4 IU/mL in all groups. LP tests showed that neutrophils and lymphocytes were in the normal range in all groups immunized with the two components vaccine. However, in the tri-components control DTaP vaccine group, as well as two- and tri-components rDTaP with beta-glucan group, a higher monocyte count was observed 3 days after vaccination, although less than 2 times the normal range. In the MWG test, both groups showed changes less than 20% in body temperature and body weight before the after the final immunizations. Inflammatory cytokines within the muscle at the injection site on day 3 after intramuscular injection revealed no significant response in all groups.
CONCLUSION
There were no findings associated with residual PTx, and no significant differences in both local and systemic adverse reactions in the novel rDTaP vaccine compared to existing available DTaP vaccines. The results suggest that the novel rDTaP vaccine is safe.
PubMed: 38752005
DOI: 10.7774/cevr.2024.13.2.155 -
Nature Medicine May 2024How human genetic variation contributes to vaccine effectiveness in infants is unclear, and data are limited on these relationships in populations with African...
How human genetic variation contributes to vaccine effectiveness in infants is unclear, and data are limited on these relationships in populations with African ancestries. We undertook genetic analyses of vaccine antibody responses in infants from Uganda (n = 1391), Burkina Faso (n = 353) and South Africa (n = 755), identifying associations between human leukocyte antigen (HLA) and antibody response for five of eight tested antigens spanning pertussis, diphtheria and hepatitis B vaccines. In addition, through HLA typing 1,702 individuals from 11 populations of African ancestry derived predominantly from the 1000 Genomes Project, we constructed an imputation resource, fine-mapping class II HLA-DR and DQ associations explaining up to 10% of antibody response variance in our infant cohorts. We observed differences in the genetic architecture of pertussis antibody response between the cohorts with African ancestries and an independent cohort with European ancestry, but found no in silico evidence of differences in HLA peptide binding affinity or breadth. Using immune cell expression quantitative trait loci datasets derived from African-ancestry samples from the 1000 Genomes Project, we found evidence of differential HLA-DRB1 expression correlating with inferred protection from pertussis following vaccination. This work suggests that HLA-DRB1 expression may play a role in vaccine response and should be considered alongside peptide selection to improve vaccine design.
Topics: Humans; HLA-DRB1 Chains; Infant; Black People; Hepatitis B Vaccines; Quantitative Trait Loci; Male; Female; Uganda; Antibody Formation; Pertussis Vaccine; Vaccination; Whooping Cough
PubMed: 38740997
DOI: 10.1038/s41591-024-02944-5 -
Microbial Genomics May 2024Cutaneous ulcers are common in yaws-endemic areas. Although often attributed to ' subsp. and , quantitative PCR has highlighted a significant proportion of these ulcers...
Using 16s rRNA sequencing to characterize the microbiome of tropical cutaneous ulcer disease: insights into the microbial landscape and implications for diagnosis and treatment.
Cutaneous ulcers are common in yaws-endemic areas. Although often attributed to ' subsp. and , quantitative PCR has highlighted a significant proportion of these ulcers are negative for both pathogens and are considered idiopathic. This is a retrospective analysis utilising existing 16S rRNA sequencing data from two independent yaws studies that took place in Ghana and the Solomon Islands. We characterized bacterial diversity in 38 samples to identify potential causative agents for idiopathic cutaneous ulcers. We identified a diverse bacterial profile, including , , , spp and , consistent with findings from previous cutaneous ulcer microbiome studies. No single bacterial species was universally present across all samples. The most prevalent bacterium, , appeared in 42% of samples, suggesting a multifactorial aetiology for cutaneous ulcers in yaws-endemic areas. This study emphasizes the need for a nuanced understanding of potential causative agents. The findings prompt further exploration into the intricate microbial interactions contributing to idiopathic yaw-like ulcers, guiding future research toward comprehensive diagnostic and therapeutic strategies.
Topics: Humans; RNA, Ribosomal, 16S; Microbiota; Skin Ulcer; Ghana; Male; Yaws; Retrospective Studies; Female; Adult; Bacteria; Melanesia; Middle Aged; Staphylococcus; Streptococcus pyogenes; Arcanobacterium; Campylobacter
PubMed: 38739120
DOI: 10.1099/mgen.0.001234 -
Advances in Nutrition (Bethesda, Md.) Jun 2024Vaccines can prevent infectious diseases, but their efficacy varies, and factors impacting vaccine effectiveness remain unclear. Iron deficiency is the most common... (Review)
Review
Vaccines can prevent infectious diseases, but their efficacy varies, and factors impacting vaccine effectiveness remain unclear. Iron deficiency is the most common nutrient deficiency, affecting >2 billion individuals. It is particularly common in areas with high infectious disease burden and in groups that are routinely vaccinated, such as infants, pregnant women, and the elderly. Recent evidence suggests that iron deficiency and low serum iron (hypoferremia) not only cause anemia but also may impair adaptive immunity and vaccine efficacy. A report of human immunodeficiency caused by defective iron transport underscored the necessity of iron for adaptive immune responses and spurred research in this area. Sufficient iron is essential for optimal production of plasmablasts and IgG responses by human B-cells in vitro and in vivo. The increased metabolism of activated lymphocytes depends on the high-iron acquisition, and hypoferremia, especially when occurring during lymphocyte expansion, adversely affects multiple facets of adaptive immunity, and may lead to prolonged inhibition of T-cell memory. In mice, hypoferremia suppresses the adaptive immune response to influenza infection, resulting in more severe pulmonary disease. In African infants, anemia and/or iron deficiency at the time of vaccination predict decreased response to diphtheria, pertussis, and pneumococcal vaccines, and response to measles vaccine may be increased by iron supplementation. In this review, we examine the emerging evidence that iron deficiency may limit adaptive immunity and vaccine responses. We discuss the molecular mechanisms and evidence from animal and human studies, highlight important unknowns, and propose a framework of key research questions to better understand iron-vaccine interactions.
Topics: Humans; Adaptive Immunity; Animals; Iron; Vaccine Efficacy; Iron Deficiencies; Anemia, Iron-Deficiency; Female; Nutritional Status; Mice; Pregnancy; Vaccination; Vaccines; Infant
PubMed: 38729263
DOI: 10.1016/j.advnut.2024.100238 -
International Journal of Public Health 2024To describe a suspected diphtheria outbreak in a Swiss asylum seeker reception centre, and to analyse its management response regarding testing and vaccination. We...
To describe a suspected diphtheria outbreak in a Swiss asylum seeker reception centre, and to analyse its management response regarding testing and vaccination. We retrospectively analysed clinical, microbiology, and case management data of all asylum seekers tested for between 28th August and 31st December 2022 while residing at the centre. Results are reported descriptively. Among 265 individuals tested, ten cases of cutaneous diphtheria, one simultaneous respiratory and cutaneous case, and nine respiratory carriers were identified. Mass throat screening, targeted throat testing and targeted wound testing yielded 4.8%, 4.3%, and 17.4% positive results, respectively. No respiratory carrier was identified among cutaneous cases undergoing a throat swab, and no symptomatic case was identified among individuals with unspecific throat symptoms. Rates of vaccination implementation of newly arriving asylum seekers before and after the outbreak were low (17.5% and 15.5%, respectively), as were rates of targeted vaccination among cases and close contacts. We provide evidence for transmission both prior to arrival and within the setting, suboptimal practices and timeliness of testing, and implementation gaps in vaccination.
Topics: Humans; Switzerland; Refugees; Diphtheria; Disease Outbreaks; Retrospective Studies; Male; Female; Adult; Adolescent; Young Adult; Vaccination; Corynebacterium diphtheriae; Middle Aged; Mass Screening
PubMed: 38721474
DOI: 10.3389/ijph.2024.1606791 -
Heliyon May 2024Trained immunity (TRAIM) or the enhanced non-specific immune response after primary stimulation by infection or vaccination is a recent but well-recognized concept. To...
Trained immunity (TRAIM) or the enhanced non-specific immune response after primary stimulation by infection or vaccination is a recent but well-recognized concept. To verify its predictions, our objective was to determine the effects of two bacterial vaccines, typhoid fever (TFV) and diphtheria-tetanus-pertussis (DTP) on the infection, hospitalization and death frequencies associated to COVID-19 in a retrospective study on subjects vaccinated or not with TFV and DTP in the 4 years prior to the start of COVID-19 pandemia in the Basque Country (Spain). The studied outcome records were split into two periods according to COVID-19 vaccination, the pre-vaccination (ACV) from March to December 2020 and the post-vaccination (PCV) from September 2021 to June 2022). In total, 13,673 subjects were vaccinated against TFV and 42,997 against DTP. A total of 2,005,084 individual records were studied in the ACV period and 1,436,693 in the PCV period. The proportion of infection, hospitalization and death associated to COVID-19 among controls in ACV was 4.97 %, 7.14 % and 3.54 %, respectively 7.20 %, 2.24 % and 0.10 % among TFV subjects. Regarding DTP, the proportions were 4.97 %, 7.12 % and 3.58 % for controls and 5.79 %, 5.79 % and 0.80 % for vaccinees. In the PCV period, the proportion of infection, hospitalization and death among controls was 21.89 %, 2.62 % and 0.92 %, respectively 31.19 %, 0.76 %, 0.00 % among TFV. For DTP, infection, hospitalization and death proportions were 21.89 %, 2.62 % and 0.92 %, respectively, among controls 32.03 %, 1.85 % and 0.24 % among vaccinated subjects. The corresponding combined ACV and PCV odds ratios (OR) for SARS-CoV2 infection were 1.505 (95%CI 1.455-1.558; p < 0.0001; reduction -41.85 %) and 1.633 (95%CI 1.603-1.662; p < 0.0001; reduction -51.74 %), for TFV and DTP, respectively. Regarding COVID-19 associated hospitalization, the OR were 0.295 (95%CI 0.220-0.396; p = 0.0001; reduction 69.74 %) and 0.667 (95%CI 0.601-0.741; p = 0.0001; reduction 32.44 %), for TFV and DTP, respectively). COVID-19 associated death OR were 0.016 (95%CI 0.002-0.113, p < 0.0001; reduction 98.38 %) and 0.212 (95%CI 0.161-0.280; p = 0.0001; reduction 78.52 %), for TFV and DTP, respectively. We conclude that TRAIM effects by TFV and DTP vaccination in the four years prior to the pandemic SARS-CoV2 were supported by slightly increased infection rates, but strongly reduced COVID-19 associated hospitalization and death rates.
PubMed: 38707311
DOI: 10.1016/j.heliyon.2024.e29935 -
Journal of Preventive Medicine and... Mar 2024In recent years, diphtheria has re-emerged in areas with inadequate vaccination coverage, and Europe has not been spared with several cases among migrants. Diphtheria is...
In recent years, diphtheria has re-emerged in areas with inadequate vaccination coverage, and Europe has not been spared with several cases among migrants. Diphtheria is a potentially fatal infection caused mainly by toxigenic strains of Corynebacterium diphtheriae. Due to the high mortality rate, especially among young children, the fight against diphtheria is considered one of the first conquests of immunization. In the history of medicine, there is a unique case of an unconventional response to a diphtheria outbreak in which sled dogs were used to overcome the supply difficulties of diphtheria antitoxin. The mass media followed the medical response to the outbreak and raised audience awareness of public health issues. The facts of Nome, Alaska, in 1925 can serve as a catalyst to rethink conventional responses to diphtheria outbreaks in low-income countries today and promote mass media awareness of public health importance.
Topics: Diphtheria; Animals; Humans; History, 20th Century; Dogs; Alaska; Togo; Corynebacterium diphtheriae; Disease Outbreaks; Diphtheria Antitoxin; Seasons
PubMed: 38706760
DOI: 10.15167/2421-4248/jpmh2024.65.1.3229 -
Microbiology Spectrum Jun 2024A US collection of invasive serotype O1 bloodstream infection (BSI) isolates were assessed for genotypic and phenotypic diversity as the basis for designing a broadly...
UNLABELLED
A US collection of invasive serotype O1 bloodstream infection (BSI) isolates were assessed for genotypic and phenotypic diversity as the basis for designing a broadly protective O-antigen vaccine. Eighty percent of the BSI isolate serotype O1 strains were genotypically ST95 O1:K1:H7. The carbohydrate repeat unit structure of the O1a subtype was conserved in the three strains tested representing core genome multi-locus sequence types (MLST) sequence types ST95, ST38, and ST59. A long-chain O1a CRM lattice glycoconjugate antigen was generated using oxidized polysaccharide and reductive amination chemistry. Two ST95 strains were investigated for use in opsonophagocytic assays (OPA) with immune sera from vaccinated animals and in murine lethal challenge models. Both strains were susceptible to OPA killing with O1a glycoconjugate post-immune sera. One of these, a neonatal sepsis strain, was found to be highly lethal in the murine challenge model for which virulence was shown to be dependent on the presence of the K1 capsule. Mice immunized with the O1a glycoconjugate were protected from challenges with this strain or a second, genotypically related, and similarly virulent neonatal isolate. This long-chain O1a CRM lattice glycoconjugate shows promise as a component of a multi-valent vaccine to prevent invasive infections.
IMPORTANCE
The serotype O1 O-antigen serogroup is a common cause of invasive bloodstream infections (BSI) in populations at risk such as newborns and the elderly. Sequencing of US BSI isolates and structural analysis of O polysaccharide antigens purified from strains that are representative of genotypic sub-groups confirmed the relevance of the O1a subtype as a vaccine antigen. O polysaccharide was purified from a strain engineered to produce long-chain O1a O-antigen and was chemically conjugated to CRM carrier protein. The resulting glycoconjugate elicited functional antibodies and was protective in mice against lethal challenges with virulent K1-encapsulated O1a isolates.
Topics: Animals; O Antigens; Mice; Escherichia coli Infections; Escherichia coli; Glycoconjugates; Humans; Serogroup; Escherichia coli Vaccines; Antibodies, Bacterial; Female; Virulence; Vaccines, Conjugate; Multilocus Sequence Typing; Disease Models, Animal; Bacteremia; Bacterial Proteins
PubMed: 38700324
DOI: 10.1128/spectrum.04213-23 -
MMWR. Morbidity and Mortality Weekly... May 2024
Topics: Humans; Corynebacterium diphtheriae; Diphtheria; Adolescent; Washington; Adult; Child; Middle Aged; Child, Preschool; Male; Young Adult; Female; Infant; Aged
PubMed: 38696348
DOI: 10.15585/mmwr.mm7317a4