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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 -
Molecular Microbiology Jun 2024Bacteria contain conserved mechanisms to control the intracellular levels of metal ions. Metalloregulatory transcription factors bind metal cations and play a central...
Bacteria contain conserved mechanisms to control the intracellular levels of metal ions. Metalloregulatory transcription factors bind metal cations and play a central role in regulating gene expression of metal transporters. Often, these transcription factors regulate transcription by binding to a specific DNA sequence in the promoter region of target genes. Understanding the preferred DNA-binding sequence for transcriptional regulators can help uncover novel gene targets and provide insight into the biological role of the transcription factor in the host organism. Here, we identify consensus DNA-binding sequences and subsequent transcription regulatory networks for two metalloregulators from the ferric uptake regulator (FUR) and diphtheria toxin repressor (DtxR) superfamilies in Thermus thermophilus HB8. By homology search, we classify the DtxR homolog as a manganese-specific, MntR (TtMntR), and the FUR homolog as a peroxide-sensing, PerR (TtPerR). Both transcription factors repress separate ZIP transporter genes in vivo, and TtPerR acts as a bifunctional transcription regulator by activating the expression of ferric and hemin transport systems. We show TtPerR and TtMntR bind DNA in the presence of manganese in vitro and in vivo; however, TtPerR is unable to bind DNA in the presence of iron, likely due to iron-mediated histidine oxidation. Unlike canonical PerR homologs, TtPerR does not appear to contribute to peroxide detoxification. Instead, the TtPerR regulon and DNA binding sequence are more reminiscent of Fur or Mur homologs. Collectively, these results highlight the similarities and differences between two metalloregulatory superfamilies and underscore the interplay of manganese and iron in transcription factor regulation.
Topics: Bacterial Proteins; Thermus thermophilus; Gene Expression Regulation, Bacterial; Repressor Proteins; Manganese; Promoter Regions, Genetic; Transcription Factors; Iron; Transcription, Genetic; DNA-Binding Proteins; Binding Sites
PubMed: 38735869
DOI: 10.1111/mmi.15278 -
Molecular Therapy : the Journal of the... May 2024HIV-1 infection remains a public health problem with no cure. Although antiretroviral therapy (ART) is effective for suppressing HIV-1 replication, it requires lifelong...
HIV-1 infection remains a public health problem with no cure. Although antiretroviral therapy (ART) is effective for suppressing HIV-1 replication, it requires lifelong drug administration due to a stable reservoir of latent proviruses and may cause serious side effects and drive the emergence of drug-resistant HIV-1 variants. Gene therapy represents an alternative approach to overcome the limitations of conventional treatments against HIV-1 infection. In this study, we constructed and investigated the antiviral effects of an HIV-1 Tat-dependent conditionally replicating adenovirus, which selectively replicates and expresses the diphtheria toxin A chain (Tat-CRAds-DTA) in HIV-1-infected cells both in vitro and in vivo. We found that Tat-CRAds-DTA could specifically induce cell death and inhibit virus replication in HIV-1-infected cells mediated by adenovirus proliferation and DTA expression. A low titer of progeny Tat-CRAds-DTA was also detected in HIV-1-infected cells. In addition, Tat-CRAds-DTA showed no apparent cytotoxicity to HIV-1-negative cells and demonstrated significant therapeutic efficacy against HIV-1 infection in a humanized mouse model. The findings in this study highlight the potential of Tat-CRAds-DTA as a new gene therapy for the treatment of HIV-1 infection.
PubMed: 38734901
DOI: 10.1016/j.ymthe.2024.05.015 -
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 -
Vaccine Jun 2024Vaccine prevention strategies play a crucial role in the management of people living with HIV (PLWH). The aim of this study was to assess vaccination coverage and...
Vaccine prevention strategies play a crucial role in the management of people living with HIV (PLWH). The aim of this study was to assess vaccination coverage and identify barriers to vaccine uptake in PLWH in the Paris region. A cross-sectional survey was conducted in PLWH in 16 hospitals in the Paris region. The vaccination status, characteristics, opinions, and behaviors of participants were collected using a face-to-face questionnaire and from medical records. A total of 338 PLWH were included (response rate 99.7 %). The median age of participants was 51 years (IQR: 41-58). Vaccination coverage was 77.3 % for hepatitis B (95 % CI: 72.3-81.8 %), 62.7 % for hepatitis A (57.3-67.9 %), 61.2 % for pneumococcal vaccines (55.8-66.5 %), 56.5 % for diphtheria/tetanus/poliomyelitis (DTP) (51.0-61.9 %), 44.7 % for seasonal influenza (39.3-50.1 %), 31.4 % for measles/mumps/rubella (26.4-36.6 %) and 38.5 % for meningococcal vaccine (13.9-68.4 %). The main reason for vaccine reluctance was related to the lack of vaccination proposals/reminders. The overall willingness to get vaccinated was 71.0 % (65.9-75.8 %). In the multivariable analysis, several factors were associated with a higher vaccine uptake; for DTP vaccine: higher education level, having vaccination records, being registered with a general practitioner; for seasonal influenza vaccine: age > 60 years, higher education level, being employed. The overall vaccination coverage was suboptimal. Development of strategies reducing missed opportunity to offer vaccines is needed.
Topics: Humans; Middle Aged; Male; Female; Adult; Vaccination Coverage; Paris; Cross-Sectional Studies; Prospective Studies; HIV Infections; Ambulatory Care Facilities; Vaccination Hesitancy; Surveys and Questionnaires; Vaccination; Patient Acceptance of Health Care
PubMed: 38714445
DOI: 10.1016/j.vaccine.2024.04.077 -
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