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Immunity May 2022Pathogenic enteric viruses are a major cause of morbidity and mortality, particularly among children in developing countries. The host response to enteric viruses occurs... (Review)
Review
Pathogenic enteric viruses are a major cause of morbidity and mortality, particularly among children in developing countries. The host response to enteric viruses occurs primarily within the mucosa, where the intestinal immune system must balance protection against pathogens with tissue protection and tolerance to harmless commensal bacteria and food. Here, we summarize current knowledge in natural immunity to enteric viruses, highlighting specialized features of the intestinal immune system. We further discuss how knowledge of intestinal anti-viral mechanisms can be translated into vaccine development with particular focus on immunization in the oral route. Research reveals that the intestine is a complex interface between enteric viruses and the host where environmental factors influence susceptibility and immunity to infection, while viral infections can have lasting implications for host health. A deeper mechanistic understanding of enteric anti-viral immunity with this broader context can ultimately lead to better vaccines for existing and emerging viruses.
Topics: Antigens, Viral; Child; Enterovirus Infections; Humans; Immunity, Innate; Intestinal Mucosa; Intestines; Vaccines; Viruses
PubMed: 35545029
DOI: 10.1016/j.immuni.2022.04.007 -
Poliomyelitis is a current challenge: long-term sequelae and circulating vaccine-derived poliovirus.GeroScience Apr 2023For more than 20 years, the World Health Organization Western Pacific Region (WPR) has been polio-free. However, two current challenges are still polio-related. First,... (Review)
Review
For more than 20 years, the World Health Organization Western Pacific Region (WPR) has been polio-free. However, two current challenges are still polio-related. First, around half of poliomyelitis elderly survivors suffer late poliomyelitis sequelae with a substantial impact on daily activities and quality of life, experiencing varying degrees of residual weakness as they age. The post-polio syndrome as well as accelerated aging may be involved. Second, after the worldwide Sabin oral poliovirus (OPV) vaccination, the recent reappearance of strains of vaccine-derived poliovirus (VDPV) circulating in the environment is worrisome and able to persistent person-to-person transmission. Such VDPV strains exhibit atypical genetic characteristics and reversed neurovirulence that can cause paralysis similarly to wild poliovirus, posing a significant obstacle to the elimination of polio. Immunization is essential for preventing paralysis in those who are exposed to the poliovirus. Stress the necessity of maintaining high vaccination rates because declining immunity increases the likelihood of reemergence. If mankind wants to eradicate polio in the near future, measures to raise immunization rates and living conditions in poorer nations are needed, along with strict observation. New oral polio vaccine candidates offer a promissory tool for this goal.
Topics: Aged; Humans; Paralysis; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Quality of Life
PubMed: 36260265
DOI: 10.1007/s11357-022-00672-7 -
Cell Host & Microbe May 2020The live-attenuated oral poliovirus vaccine (OPV or Sabin vaccine) replicates in gut-associated tissues, eliciting mucosa and systemic immunity. OPV protects from...
The live-attenuated oral poliovirus vaccine (OPV or Sabin vaccine) replicates in gut-associated tissues, eliciting mucosa and systemic immunity. OPV protects from disease and limits poliovirus spread. Accordingly, vaccination with OPV is the primary strategy used to end the circulation of all polioviruses. However, the ability of OPV to regain replication fitness and establish new epidemics represents a significant risk of polio re-emergence should immunization cease. Here, we report the development of a poliovirus type 2 vaccine strain (nOPV2) that is genetically more stable and less likely to regain virulence than the original Sabin2 strain. We introduced modifications within at the 5' untranslated region of the Sabin2 genome to stabilize attenuation determinants, 2C coding region to prevent recombination, and 3D polymerase to limit viral adaptability. Prior work established that nOPV2 is immunogenic in preclinical and clinical studies, and thus may enable complete poliovirus eradication.
Topics: Adult; Animals; Chlorocebus aethiops; Disease Models, Animal; Female; Genetic Engineering; HeLa Cells; Humans; Immunogenicity, Vaccine; Male; Mice; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; RNA, Viral; RNA-Dependent RNA Polymerase; Recombination, Genetic; Vaccination; Vaccines, Attenuated; Vero Cells; Virulence
PubMed: 32330425
DOI: 10.1016/j.chom.2020.04.003 -
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 -
Microorganisms May 2023Poliovirus (PV), the virus that causes both acute poliomyelitis and post-polio syndrome, is classified within the species, and there are three wild PV serotypes: WPV1,... (Review)
Review
Poliovirus (PV), the virus that causes both acute poliomyelitis and post-polio syndrome, is classified within the species, and there are three wild PV serotypes: WPV1, WPV2 and WPV3. The launch of the Global Polio Eradication Initiative (GPEI) in 1988 eradicated two of the three serotypes of WPV (WPV2 and WPV3). However, the endemic transmission of WPV1 persists in Afghanistan and Pakistan in 2022. There are cases of paralytic polio due to the loss of viral attenuation in the oral poliovirus vaccine (OPV), known as vaccine-derived poliovirus (VDPV). Between January 2021 and May 2023, a total of 2141 circulating VDPV (cVDPV) cases were reported in 36 countries worldwide. Because of this risk, inactivated poliovirus (IPV) is being used more widely, and attenuated PV2 has been removed from OPV formulations to obtain bivalent OPV (containing only types 1 and 3). In order to avoid the reversion of attenuated OPV strains, the new OPV, which is more stable due to genome-wide modifications, as well as sabin IPV and virus-like particle (VLP) vaccines, is being developed and offers promising solutions for eradicating WP1 and VDPV.
PubMed: 37317297
DOI: 10.3390/microorganisms11051323 -
Mucosal Immunology Jan 2022A cornerstone of the global initiative to eradicate polio is the widespread use of live and inactivated poliovirus vaccines in extensive public health campaigns designed... (Review)
Review
A cornerstone of the global initiative to eradicate polio is the widespread use of live and inactivated poliovirus vaccines in extensive public health campaigns designed to prevent the development of paralytic disease and interrupt transmission of the virus. Central to these efforts is the goal of inducing mucosal immunity able to limit virus replication in the intestine. Recent clinical trials have evaluated new combined regimens of poliovirus vaccines, and demonstrated clear differences in their ability to restrict virus shedding in stool after oral challenge with live virus. Analyses of mucosal immunity accompanying these trials support a critical role for enteric neutralizing IgA in limiting the magnitude and duration of virus shedding. This review summarizes key findings in vaccine-induced intestinal immunity to poliovirus in infants, older children, and adults. The impact of immunization on development and maintenance of protective immunity to poliovirus and the implications for global eradication are discussed.
Topics: Animals; Antibodies, Neutralizing; Antibodies, Viral; Child; Humans; Immunity, Mucosal; Immunoglobulin A; Poliomyelitis; Poliovirus; Vaccination; Viral Vaccines; Virus Shedding
PubMed: 34239028
DOI: 10.1038/s41385-021-00428-0 -
Bulletin of the World Health... Dec 2023A decrease in vaccine coverage in conflict-affected areas has placed Yemen at higher risk of polio outbreaks caused by vaccine-derived poliovirus strains.
PROBLEM
A decrease in vaccine coverage in conflict-affected areas has placed Yemen at higher risk of polio outbreaks caused by vaccine-derived poliovirus strains.
APPROACH
In response to polio outbreaks, the Yemeni health ministry and partners initiated multiple vaccination campaigns to deliver vaccines to children. We also implemented several measures to enhance communication, education, health promotion and hygiene, especially in camps for internally displaced people.
LOCAL SETTING
In 2009, Yemen achieved polio-free status and maintained it until 2019. However, the ongoing political conflict since 2015, coupled with challenges in delivering the polio vaccine to conflict-affected areas, resulted in two polio outbreaks: 35 cases caused by vaccine-derived poliovirus strain 1 between 2019 and 2021, and 230 cases due to vaccine-derived poliovirus strain 2 between November 2021 and December 2022.
RELEVANT CHANGES
In response to the first outbreak, by the end of 2020, we vaccinated 7.2 million children through nationwide vaccination campaigns, except in Sa'ada governorate due to a ban by the authorities. By the end of 2021, 3 800 313 children younger than 5 years had received polio vaccines. For the second outbreak, by the end of 2022, 4 463 389 vaccines had been given to children younger than 10 years, and 1 217 423 to those younger than 5 years.
LESSONS LEARNT
Vaccination campaigns in conflict-affected areas with low vaccine coverage remain crucial in eradicating polio. Efforts are needed to reach vulnerable groups such as displaced populations. Advocacy, communication and social mobilization actions help ensure broader public inclusion and participation in vaccination efforts to prevent polio outbreaks.
Topics: Child; Humans; Yemen; Poliomyelitis; Poliovirus; Poliovirus Vaccines; Disease Outbreaks
PubMed: 38024246
DOI: 10.2471/BLT.23.290122 -
Pediatrics May 2022The majority of children are prescribed antibiotics in the first 2 years of life while vaccine-induced immunity develops. Researchers have suggested a negative...
BACKGROUND
The majority of children are prescribed antibiotics in the first 2 years of life while vaccine-induced immunity develops. Researchers have suggested a negative association of antibiotic use with vaccine-induced immunity in adults, but data are lacking in children.
METHODS
From 2006 to 2016, children aged 6 to 24 months were observed in a cohort study. A retrospective, unplanned secondary analysis of the medical record regarding antibiotic prescriptions and vaccine antibody measurements was undertaken concurrently. Antibody measurements relative to diphtheria-tetanus-acellular pertussis (DTaP), inactivated polio (IPV), Haemophilus influenzae type b (Hib), and pneumococcal conjugate (PCV) vaccines were made.
RESULTS
In total, 560 children were compared (342 with and 218 without antibiotic prescriptions). Vaccine-induced antibody levels to several DTaP and PCV antigens were lower (P < .05) in children given antibiotics. A higher frequency of vaccine-induced antibodies below protective levels in children given antibiotics occurred at 9 and 12 months of age (P < .05). Antibiotic courses over time was negatively associated with vaccine-induced antibody levels. For each antibiotic course the child received, prebooster antibody levels to DTaP antigens were reduced by 5.8%, Hib by 6.8%, IPV by 11.3%, and PCV by 10.4% (all P ≤ .05), and postbooster antibody levels to DTaP antigens were reduced by 18.1%, Hib by 21.3%, IPV by 18.9%, and PCV by 12.2% (all P < .05).
CONCLUSIONS
Antibiotic use in children <2 years of age is associated with lower vaccine-induced antibody levels to several vaccines.
Topics: Anti-Bacterial Agents; Antibodies, Viral; Child; Child, Preschool; Cohort Studies; Diphtheria-Tetanus-acellular Pertussis Vaccines; Haemophilus Vaccines; Humans; Poliovirus Vaccine, Inactivated; Retrospective Studies; Vaccines, Combined
PubMed: 35474546
DOI: 10.1542/peds.2021-052061