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Journal of Neurochemistry Sep 2021Tetanus is a deadly but preventable disease caused by a protein neurotoxin produced by Clostridium tetani. Spores of C. tetani may contaminate a necrotic wound and... (Review)
Review
Tetanus is a deadly but preventable disease caused by a protein neurotoxin produced by Clostridium tetani. Spores of C. tetani may contaminate a necrotic wound and germinate into a vegetative bacterium that releases a toxin, termed tetanus neurotoxin (TeNT). TeNT enters the general circulation, binds to peripheral motor neurons and sensory neurons, and is transported retroaxonally to the spinal cord. It then enters inhibitory interneurons and blocks the release of glycine or GABA causing a spastic paralysis. This review attempts to correlate the metalloprotease activity of TeNT and its trafficking and localization into the vertebrate body to the nature and sequence of appearance of the symptoms of tetanus.
Topics: Animals; Brain; Humans; Neurotoxins; Peripheral Nerves; Spinal Cord; Tetanus; Tetanus Toxin; Tetanus Toxoid
PubMed: 33629408
DOI: 10.1111/jnc.15330 -
MBio Aug 2020Chemically inactivated tetanus toxoid (CITT) is clinically effective and widely used. However, CITT is a crude nonmalleable vaccine that contains hundreds of proteins,...
Chemically inactivated tetanus toxoid (CITT) is clinically effective and widely used. However, CITT is a crude nonmalleable vaccine that contains hundreds of proteins, and the active component is present in variable and sometimes minor percentages of vaccine mass. Recombinant production of a genetically inactivated tetanus vaccine offers an opportunity to replace and improve the current tetanus vaccine. Previous studies showed the feasibility of engineering full-length tetanus toxin (TT) in In the present study, full-length TT was engineered with eight individual amino acid mutations (8MTT) to inactivate catalysis, translocation, and host receptor-binding functions, retaining 99.4% amino acid identity to native tetanus toxin. 8MTT purified as a 150-kDa single-chain protein, which trypsin nicked to a 100-kDa heavy chain and 50-kDa light chain. The 8MTT was not toxic for outbred mice and was >50 million-fold less toxic than native TT. Relative to CITT, 8MTT vaccination elicited a strong immune response and showed good vaccine potency against TT challenge. The strength of the immune response to both vaccines varied among individual outbred mice. These data support 8MTT as a candidate vaccine against tetanus and a malleable candidate conjugate vaccine platform to enhance the immune response to polysaccharides and other macromolecular molecules to facilitate a rapid response to emerging microbial pathogens. Chemical inactivation is a clinically effective mechanism to detoxify protein toxins to produce vaccines against microbial infections and to serve as a platform for production of conjugate polysaccharide vaccines. This method is widely used for the production of protein toxin vaccines, including tetanus toxoid. However, chemical modification alters the protein structure with unknown effects on antigenicity. Here, a recombinant full-length tetanus toxin (TT) is engineered with 8 mutations (8MTT) that inactivate three toxin functions: catalysis, translocation, and receptor binding. 8MTT is nontoxic and elicits a potent immune response in outbred mice. 8MTT also represents a malleable platform for the production of conjugate vaccines, which can facilitate a rapid vaccine response against emerging microbial pathogens.
Topics: Animals; Antibodies, Bacterial; Escherichia coli; Female; Mice; Mice, Inbred ICR; Mutation; Recombinant Proteins; Tetanus; Tetanus Toxoid; Vaccination; Vaccine Potency
PubMed: 32788381
DOI: 10.1128/mBio.01668-20 -
Journal of Neurology, Neurosurgery, and... Sep 2000
Review
Topics: Adolescent; Child; Child, Preschool; Global Health; Health Policy; Humans; Infant; Infant, Newborn; Intensive Care Units, Neonatal; Tetanus; Tetanus Toxoid
PubMed: 10945801
DOI: 10.1136/jnnp.69.3.292 -
The Journal of Infectious Diseases Jun 2022Prevention of respiratory syncytial virus (RSV) disease in infants is an unmet vaccine need, and maternal immunization is a potential strategy to address this need. This...
BACKGROUND
Prevention of respiratory syncytial virus (RSV) disease in infants is an unmet vaccine need, and maternal immunization is a potential strategy to address this need. This study evaluated concomitant administration of RSV stabilized prefusion F subunit vaccine (RSVpreF) and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine adsorbed (Tdap) in healthy, nonpregnant women 18‒49 years of age.
METHODS
In this phase 2b, multicenter, placebo-controlled, observer-blind, noninferiority study, participants were randomized to receive RSVpreF in a range of doses and formulations with Tdap or alone, or Tdap alone. Safety and immunogenicity were assessed.
RESULTS
Local reactions and systemic events were generally similar across vaccine groups. Noninferiority of anti-RSV-A and anti-RSV-B immune responses induced by RSVpreF with Tdap was demonstrated compared to RSVpreF alone. Noninferiority of anti-diphtheria toxoid and anti-tetanus toxoid immune responses after administration of RSVpreF with Tdap was demonstrated compared to Tdap alone; noninferiority was not met for anti-pertussis component responses.
CONCLUSIONS
RSVpreF was safe and well tolerated when administered with Tdap or alone in nonpregnant women 18‒49 years of age. Immune responses induced by Tdap administered with RSVpreF were noninferior for the tetanus and diphtheria components of Tdap, but not for pertussis.
CLINICAL TRIALS REGISTRATION
NCT04071158.
Topics: Adult; Antibodies, Bacterial; Antibodies, Viral; Diphtheria; Diphtheria Toxoid; Diphtheria-Tetanus-acellular Pertussis Vaccines; Female; Humans; Immunogenicity, Vaccine; Middle Aged; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Tetanus; Whooping Cough; Young Adult
PubMed: 34637519
DOI: 10.1093/infdis/jiab505 -
British Medical Bulletin 2015The causative agent of tetanus, Clostridium tetani is widespread in the environment throughout the world and cannot be eradicated. To reduce the number of cases of... (Review)
Review
INTRODUCTION
The causative agent of tetanus, Clostridium tetani is widespread in the environment throughout the world and cannot be eradicated. To reduce the number of cases of tetanus efforts are focussed on prevention using vaccination and post-exposure wound care.
SOURCES OF DATA
Medline, Pubmed and Cochrane databases; World Health Organization and United Nations Children's Fund publications.
AREAS OF AGREEMENT
The maternal and neonatal tetanus elimination initiative has resulted in significant reductions in mortality from neonatal tetanus throughout the world.
AREAS OF CONTROVERSY
Although there are few data available it is likely that large numbers of children and adults, particularly men, remain unprotected due to lack of booster immunization.
AREAS TIMELY FOR DEVELOPING RESEARCH
It remains unclear how HIV and malaria affect both responses to vaccination and transplacental transfer of antibodies or how this might affect timing of vaccination doses.
Topics: Coinfection; Female; HIV Infections; Humans; Malaria; Pregnancy; Prenatal Exposure Delayed Effects; Tetanus; Tetanus Toxoid; Vaccination
PubMed: 26598719
DOI: 10.1093/bmb/ldv044 -
Human Vaccines & Immunotherapeutics Jun 2021: Diphtheria-tetanus-pertussis (DTP) vaccine has already been involved in national vaccination program for several decades in China. The immunity against these diseases...
: Diphtheria-tetanus-pertussis (DTP) vaccine has already been involved in national vaccination program for several decades in China. The immunity against these diseases in the people of all ages is not well investigated.: Serum samples were tested for IgG antibodies to diphtheria toxoid (DT), tetanus toxoid (TT) and pertussis toxin (PT) by using commercial ELISA kits.: A total of 666 sera of patients from 1 day to 89 years of age was collected from 2018 to 2019. The protective rates of diphtheria, tetanus and pertussis were 45.5%, 54.4% and 4.7%, respectively. Only 4.7% of the study population had seropositivity against three of the diseases. Young infant (<3 m) and adult (>18y) were generally lack of protective antibody against diphtheria (81.7% and 58.3%) and tetanus (91.5% and 86.2%). An obvious increase in immunity level of diphtheria and tetanus was observed at 3 m-3y, but there was no significant increase of immunity to pertussis at any age group. All age groups showed low immunity to pertussis.: The present results revealed the susceptibility to diphtheria and tetanus in young infants and adults, and the susceptibility to pertussis over the ages, which highlight the need to improve the current vaccination program.
Topics: Adult; Antibodies, Bacterial; China; Diphtheria; Diphtheria-Tetanus-Pertussis Vaccine; Humans; Infant; Tetanus; Vaccination; Whooping Cough
PubMed: 33517831
DOI: 10.1080/21645515.2020.1840253 -
CMAJ : Canadian Medical Association... Jan 2018
Topics: Animals; Anti-Bacterial Agents; Bites and Stings; Dogs; Facial Injuries; Genitalia; Humans; Post-Exposure Prophylaxis; Rabies; Rabies Vaccines; Tetanus; Tetanus Toxoid
PubMed: 29378871
DOI: 10.1503/cmaj.170684 -
Clinical and Experimental Immunology Jan 2017Besides immunizations against influenza, Streptococcus pneumoniae and herpes zoster, which are recommended specifically for elderly people, regular booster vaccinations... (Review)
Review
Besides immunizations against influenza, Streptococcus pneumoniae and herpes zoster, which are recommended specifically for elderly people, regular booster vaccinations against tetanus, diphtheria and in some cases pertussis and polio are recommended in many European countries for adults, including elderly people. Vaccination recommendations for adults differ greatly between individual countries and coverage data is scarce. Tetanus-specific antibody concentrations are generally higher than diphtheria-specific antibodies, and a substantial proportion of adults, and particularly of elderly people, do not have protective antibody concentrations against diphtheria. Antibody levels increase upon booster vaccination in all age groups, but diphtheria-specific antibody concentrations remain below protective levels in some older individuals, even immediately after vaccination and long-term protection is frequently not achieved. Future vaccination strategies should therefore include regular and well-documented booster shots, e.g. against tetanus and diphtheria, throughout life.
Topics: Adult; Aged; Animals; Diphtheria; Europe; Humans; Immunity, Humoral; Immunization, Secondary; Immunosenescence; Tetanus; Tetanus Toxoid; Vaccination
PubMed: 27279025
DOI: 10.1111/cei.12822 -
MMWR. Morbidity and Mortality Weekly... Mar 2022Maternal and neonatal tetanus (MNT)* remains a major cause of neonatal mortality with an 80%-100% case-fatality rate among insufficiently vaccinated mothers after...
Maternal and neonatal tetanus (MNT)* remains a major cause of neonatal mortality with an 80%-100% case-fatality rate among insufficiently vaccinated mothers after unhygienic deliveries, especially in low-income countries (1). In 1989, the World Health Assembly endorsed elimination of neonatal tetanus; the activity was relaunched in 1999 as the MNT elimination (MNTE) initiative, targeting 59 priority countries. MNTE strategies include 1) achieving ≥80% coverage with ≥2 doses of tetanus toxoid-containing vaccine (TTCV2+)** among women of reproductive age through routine and supplementary immunization activities (SIAs) in high-risk districts, 2) achieving ≥70% of deliveries by a skilled birth attendant, and 3) implementing neonatal tetanus case-based surveillance (2). This report summarizes progress toward achieving and sustaining MNTE during 2000-2020 and updates a previous report (3). By December 2020, 52 (88%) of 59 priority countries had conducted TTCV SIAs. Globally, infants protected at birth*** against tetanus increased from 74% (2000) to 86% (2020), and deliveries assisted by a skilled birth attendant increased from 64% (2000-2006) to 83% (2014-2020). Reported neonatal tetanus cases worldwide decreased by 88%, from 17,935 (2000) to 2,229 (2020), and estimated deaths decreased by 92%, from 170,829 (2000) to 14,230 (2019). By December 2020, 47 (80%) of 59 priority countries were validated to have achieved MNTE, five of which conducted postvalidation assessments. To achieve elimination in the 12 remaining countries and sustain elimination, innovation is needed, including integrating SIAs to cover multiple vaccine preventable diseases and implementing TTCV life course vaccination.
Topics: Adult; Developing Countries; Disease Eradication; Female; Health Priorities; Humans; Immunization Programs; Infant Health; Infant, Newborn; Maternal Health; Middle Aged; Tetanus; Tetanus Toxoid; Vaccination Coverage
PubMed: 35298457
DOI: 10.15585/mmwr.mm7111a2 -
The Pan African Medical Journal 2017Despite the availability of effective tetanus prevention strategies, as of 2016, Maternal and Neonatal Tetanus Elimination (MNTE) has not yet been achieved in 18... (Review)
Review
Despite the availability of effective tetanus prevention strategies, as of 2016, Maternal and Neonatal Tetanus Elimination (MNTE) has not yet been achieved in 18 countries globally. In this paper, we review the status of MNTE in the World Health Organization African Region (AFR),and provide recommendations for achieving and maintaining MNTE in AFR. As of November 2016, 37 (79%) AFR countries have achieved MNTE, with 10 (21%) countries remaining. DTP3 coverage increased from 52% in 2000 to 76% in 2015. In 2015, coverage with at least 2 doses of tetanus containing vaccine (TT2+) and proportion of newborns protected at birth (PAB) were 69% and 77%, compared with 44% and 62% in 2000, respectively. Since 1999, over 79 million women of reproductive age (WRA) have been vaccinated with TT2+ through supplementary immunization activities (SIAs). Despite the progress, only 54% of births were attended by skilled birth attendants (SBAs), 5 (11%) countries provided the 3 WHO-recommended booster doses to both sexes, and about 5.5 million WRA still need to be reached with SIAs. Coverage disparities still exist between countries that have achieved MNTE and those that have not. In 2015, coverage with DTP3 and PAB were higher in MNTE countries compared with those yet to achieve MNTE: 84% vs. 68% and 86% vs. 69%, respectively. Challenges to achieving MNTE in the remaining AFR countries include weak health systems, competing priorities, insufficient funding, insecurity, and sub-optimal neonatal tetanus (NT) surveillance. To achieve and maintain MNTE in AFR, increasing SBAs and tetanus vaccination coverage, integrating tetanus vaccination with other opportunities (e.g., polio and measles campaigns, mother and child health days), and providing appropriately spaced booster doses are needed. Strengthening NT surveillance and conducting serosurveys would ensure appropriate targeting of MNTE activities and high-quality information for validating the achievement and maintenance of elimination.
Topics: Africa; Disease Eradication; Female; Humans; Immunization Schedule; Infant, Newborn; Infant, Newborn, Diseases; Male; Pregnancy; Tetanus; Tetanus Toxoid; Vaccination; Vaccination Coverage; World Health Organization
PubMed: 29296159
DOI: 10.11604/pamj.supp.2017.27.3.11783