Polio Type Research Articles

Vaccine Potency and Structure of Yeast-Produced Polio Type 2 Stabilized Virus-like Particles.

Poliovirus (PV) is on the brink of eradication due to global vaccination programs utilizing live-attenuated oral and inactivated polio vaccines. Recombinant PV virus-like particles (VLPs) are emerging as a safe next-generation vaccine candidate for the impending polio-free era. In this study, we investigate the production, antigenicity, thermostability, immunogenicity, and structures of VLPs derived from PV serotype 2 (PV2) wildtype strain and thermally stabilized mutant (wtVLP and sVLP, respectively). Both PV2 wtVLP and sVLP are efficiently produced in Pichia pastoris yeast. The PV2 sVLP displays higher levels of D-antigen and significantly enhanced thermostability than the wtVLP. Unlike the wtVLP, the sVLP elicits neutralizing antibodies in mice at levels comparable to those induced by inactivated polio vaccine. The addition of an aluminum hydroxide adjuvant to sVLP results in faster induction and a higher magnitude of neutralizing antibodies. Furthermore, our cryo-EM structural study of both sVLP and wtVLP reveals a native conformation for the sVLP and a non-native expanded conformation for the wtVLP. Our work not only validates the yeast-produced PV2 sVLP as a promising vaccine candidate with high production potential but also sheds light on the structural mechanisms that underpin the assembly and immunogenicity of the PV2 sVLP. These findings may expedite the development of sVLP-based PV vaccines.

Global and regional burden of vaccine-associated facial paralysis, 1967-2023: Findings from the WHO international pharmacovigilance database.

The scarce and conflicting data on vaccine-associated facial paralysis limit our understanding of vaccine safety on a global scale. Therefore, this study aims to evaluate the global burden of vaccine-associated facial paralysis and to identify the extent of its association with individual vaccines, thereby contributing to the development of a more effective vaccination program. We used data on vaccine-associated facial paralysis from 1967 to 2023 (total reports, n = 131 255 418 418) from the World Health Organization International Pharmacovigilance Database. Global reporting counts, reported odds ratios (ROR), and information components (ICs) were computed to elucidate the association between the 16 vaccines and the occurrence of vaccine-associated facial paralysis across 156 countries. We identified 26 197 reports (men, n = 10 507 [40.11%]) of vaccine-associated facial paralysis from 49 537 reports of all-cause facial paralysis. Vaccine-associated facial paralysis has been consistently reported; however, a pronounced increase in reported incidence has emerged after the onset of the coronavirus disease 2019 (COVID-19) pandemic, which is attributable to the COVID-19 mRNA vaccine. Most vaccines were associated with facial paralysis, with differing levels of association, except for tuberculosis vaccines. COVID-19 mRNA vaccines had the highest association with facial paralysis reports (ROR, 28.31 [95% confidence interval, 27.60-29.03]; IC, 3.37 [IC0.25, 3.35]), followed by encephalitis, influenza, hepatitis A, papillomavirus, hepatitis B, typhoid, varicella-zoster, meningococcal, Ad-5 vectored COVID-19, measles, mumps and rubella, diphtheria, tetanus toxoids, pertussis, polio, and Hemophilus influenza type b, pneumococcal, rotavirus diarrhea, and inactivated whole-virus COVID-19 vaccines. Concerning age- and sex-specific risks, vaccine-associated facial paralysis was more strongly associated with older age groups and males. The serious adverse outcome and death rate of vaccine-associated facial paralysis were extremely low (0.07% and 0.00%, respectively). An increase in vaccine-induced facial paralysis, primarily owing to COVID-19 mRNA vaccines, was observed with most vaccines, except tuberculosis vaccines. Given the higher association observed in the older and male groups with vaccine-associated facial paralysis, close monitoring of these demographics when administering vaccines that are significantly associated with adverse reactions is crucial.

Changes in vaccination practices among infants after the introduction of DTaP-IPV/Hib combination vaccines

BackgroundDiphtheria-tetanus-acellular pertussis, polio, and Haemophilus influenza type B (DTaP-IPV/Hib) combination vaccine was introduced as a part of the Korea National Immunization Program (NIP) on June 19, 2017. Combination vaccines can improve vaccination rates by simplifying the vaccination schedule. ObjectiveTo explain how the introduction of DTaP-IPV/Hib in the NIP has changed vaccination practices for infants. MethodsUsing a nationwide vaccine registry, the proportion of infants who completed the full recommended doses of the primary series of DTaP, IPV, and Hib (D-I-H) within 12 months of age was estimated among those born between 2013 and 2019. Among those, the proportions of those who received the same DTaP components for all 3 doses during the primary series were calculated for the 2013–2016 and the 2017–2019 birth cohorts. Those who received the same component of DTaP throughout the entire primary vaccination schedule were categorized into 3 groups by DTaP components to compare the average frequency of medical visits for vaccination. ResultsA total of 2,703,822 infants were born between 2013 and 2019, of which 96.7% completed full doses of the primary D-I-H series within 12 months of age. For the 2013–2016 birth cohorts, most received DTaP-IPV-only (75.4%), while most of the 2017–2019 birth cohorts received DTaP-IPV/Hib-only (81.0%) to complete the 3 doses for primary D-I-H series. The average frequency of medical visits for vaccination showed a significant difference across the 3 groups classified by DTaP components in every birth cohort (p < 0.001). ConclusionsAfter the introduction of DTaP-IPV/Hib, most infants completed the primary D-I-H series with the combination vaccine and there was a significant reduction in the average number of medical visits for vaccination. Our findings provide important insights for countries considering the introduction of combination vaccines into their NIP.

Safety and immunogenicity of shorter interval schedules of the novel oral poliovirus vaccine type 2 in infants: a phase 3, randomised, controlled, non-inferiority study in the Dominican Republic

The novel oral poliovirus vaccine type 2 (nOPV2) is now authorised by a WHO emergency use listing and widely distributed to interrupt outbreaks of circulating vaccine-derived poliovirus type 2. As protection of vulnerable populations, particularly young infants, could be facilitated by shorter intervals between the two recommended doses, we aimed to assess safety and non-inferiority of immunogenicity of nOPV2 in 1-week, 2-week, and 4-week schedules. In this phase 3, open-label, randomised trial, healthy, full-term, infants aged 6-8 weeks from a hospital or a clinic in the Dominican Republic were randomly allocated (1:1:1 ratio) using a pre-prepared, computer-generated randomisation schedule to three groups to receive two doses of nOPV2 immunisations with a 1-week interval (group A), 2-week interval (group B), or 4-week interval (group C). The nOPV2 vaccine was given at a 0·1 mL dose and contained at least 105 50% cell culture infective dose. Neutralising antibodies against poliovirus types 1, 2, and 3 were measured before each immunisation and 4 weeks after the second dose. The primary outcome was the type 2 seroconversion rate 28 days after the second dose, and the non-inferiority margin was defined as a lower bound 95% CI of greater than -10%. Safety and reactogenicity were assessed through diary cards completed by the parent or guardian. The trial is registered with ClinicalTrials.gov, NCT05033561. We enrolled 905 infants between Dec 16, 2021, and March 28, 2022. 872 infants were included in the per-protocol analyses: 289 in group A, 293 in group B, and 290 in group C. Type 2 seroconversion rates were 87·5% (95% CI 83·2 to 91·1) in group A (253 of 289 participants), 91·8% (88·1 to 94·7) in group B (269 of 293 participants), and 95·5% (92·5 to 97·6) in group C (277 of 290 participants). Non-inferiority was shown for group B compared with group C (difference in rates -3·7; 95% CI -7·9 to 0·3), but not for group A compared with group C (-8·0; -12·7 to -3·6). 4 weeks after the second nOPV2 dose, type 2 neutralising antibodies increased in all three groups such that over 95% of each group was seroprotected against polio type 2, although final geometric mean titres tended to be highest with longer intervals between doses. Immunisation with nOPV2 was well tolerated with no causal association to vaccination of any severe or serious adverse event; one death from septic shock during the study was unrelated to the vaccine. Two nOPV2 doses administered 1 week or 2 weeks apart from age 6 weeks to 8 weeks were safe and immunogenic. Immune responses after a 2-week interval were non-inferior to those after the standard 4-week interval, but marked responses after a 1-week interval suggest that schedules with an over 1-week interval can be used to provide flexibility to campaigns to improve coverage and hasten protection during circulating vaccine-derived poliovirus type 2 outbreaks. Bill & Melinda Gates Foundation.

Vaccination coverage of children with rheumatic diseases compared with healthy controls: a retrospective case-control study

ABSTRACT Objective To reveal the vaccination status of patients with pediatric rheumatic disease (PedRD) and to compare this with healthy controls. Methods The electronic health records of the Ministry of Health regarding the vaccination status of children with PedRD followed in a tertiary hospital were analyzed cross-sectionally and compared with their healthy controls. The missing vaccines were reported according to individual, age-appropriate schedule and causes of skipped vaccines in both groups were investigated with an online survey. Results The vaccination rate of patients in the last examination was 71.4% (90/126) and 95.7% (110/115) in healthy controls (p < 0.001). Measles-mumps-rubella vaccine, diphtheria, the administration rates of the second dose of tetanus-acellular pertussis-inactivated polio and Haemophilus influenzae type B, chickenpox, and hepatitis A vaccines were significantly lower in patients than in controls (p values 0.004, 0.02, 0.01, 0.013, respectively). The pre-diagnosis incomplete vaccination proportion was significantly higher in the patient group (16.6%) than in healthy controls (4.3%) (p = 0.002). In the patient group, the proportion of incomplete live-attenuated vaccines after diagnosis (25%) was more than pre-diagnosis (61.1%) (p = 0.04), while the proportion of incomplete non-live vaccines before and after diagnosis was similar (47.2% and 50%, respectively) (p = 0.73). The major reasons for missed vaccines were physicians’ recommendations (15.6%), the presence of PedRD diagnosis (12.5%), and the drugs used (12.5%). Conclusion Vaccination coverage of PedRD patients has been shown to lag behind the routine vaccination schedule (71.4%). In addition to new recommendations, electronic health system records for vaccination may be appropriate for the follow-up of these patients, and the addition of reminder alerts may be useful to reduce the rate of missed vaccinations.

Polio type 2 and 3 eradication: Relevance to the immunity status of individuals living in Germany, 2005-2020.

Since October 2019, poliovirus type 3 (PV3) has been certified as globally eradicated, and further laboratory use of PV3 will be restricted according to the WHO Polio Eradication Initiative and containment measures. To examine a possible gap in PV3 immunity and a lack of immunity against poliovirus type 2 (PV2), which was already declared as eradicated in 2015, neutralising antibodies against polioviruses (PV) of individuals living in Germany (n=91,530 samples; mainly outpatients (≈90%) who received immune status testing) were investigated from 2005 to 2020 (age distribution: <18 years 15.8%, 18-64 years 71.2% and ≥65 years 9.5% for 2005-2015; <18 years 19.6%, 18-64 years 67% and ≥65 years 11.5% for 2016-2020). The results showed that the proportion of sera exclusively lacking antibodies against PV3 was 10.6% in 2005-2015 and 9.6% in 2016-2020 and against PV2 2.8% in 2005-2015. As there is decreased protection against PV3 and to detect potential antigenically (immune escape) variant PVs not covered by used vaccines, we recommend continued testing of PV1 and PV3.

Immunogenicity and Safety of a Quadrivalent Meningococcal Tetanus Toxoid­-Conjugate Vaccine (MenACYW­-TT) Administered Concomitantly with Pneumococcal Conjugate Vaccine in Healthy Toddlers in the Russian Federation: a Phase III Randomized Study

Relevance. Invasive meningococcal disease (IMD) has high morbidity and mortality, with infants and young children among those at greatest risk.Materials &amp; Methods. A phase III, open-­label, randomized study in toddlers aged 12–23 months evaluated the immunogenicity and safety of MenACYW­TT, a tetanus toxoid conjugated vaccine against meningococcal serogroups A, C, W, and Y, when coadministered with paediatric vaccines (measles, mumps and rubella [MMR]; varicella [V] in South Korea and Thailand; 6­in­1 combination vaccine against diphtheria, tetanus, pertussis, polio, hepatitis B and Haemophilus influenzae type b [DTaP­IPVHepB­Hib] in Mexico and pneumococcal conjugate vaccine [PCV13]) in the Russian Federation (NCT03205371). This manuscript reports the outcome of the part of the study conducted in the Russian Federation using PCV13 as the co­administered vaccine. Immunogenicity to each meningococcal serogroup was assessed by serum bactericidal antibody assay using human complement (hSBA) and, for a subset of subjects, baby rabbit complement (rSBA). Vaccine safety profiles were described up to 30 days postvaccination.Results. A total of 1,183 participants were enrolled in the study, out of which 400 were from the Russian Federation. The proportion with seroprotection (hSBA ≥1:8) to each meningococcal serogroup at Day 30 was comparable between the MenACYW­-TT and MenACYW-­TT + PCV13 groups (≥91% and ≥84%, respectively). The safety profiles of MenACYW­-TT and PCV13, when given alone or concomitantly, were generally comparable.Conclusion. Coadministration of MenACYW­-TT with pneumococcal conjugate vaccine in toddlers had no clinically relevant effect on the immunogenicity and safety of any of the vaccines.

Safety and immunogenicity of a combined DTacP-sIPV-Hib vaccine in animal models

ABSTRACT The DTacP-sIPV-Hib combination vaccine can replace the single-component acellular pertussis, diphtheria, tetanus, polio, and Haemophilus influenzae type B vaccines. In this study, we evaluated the safety and immunogenicity of a newly developed DTacP-sIPV-Hib combination vaccine in animal models. We used 40 mice and 46 cynomolgus monkeys to evaluate acute and long-term toxicity. Thirty-six guinea pigs were used for sensitization assessment. For immunogenicity assessment, 50 NIH mice and 50 rats were equally randomized to receive 3 doses of 3 different batches of the tested vaccine at an interval of 21 d, or physiological saline solution (0.5 mL). Orbital blood was collected at an interval of 21 d post inoculation to detect related antibody titers or neutralizing antibody titers against poliovirus. Gross autopsy and histopathological examination revealed no abnormal toxicity or irritation in mice and cynomolgus monkeys. Sensitization assessment in guinea pigs indicated the lack of evident allergic symptoms in the high- and low-dose vaccine groups within 30 min after repeated stimulation. The DTacP-sIPV-Hib combination vaccine induced significant immune responses in mice, rats, and cynomolgus monkeys, with 100% seroconversion rates after 3 doses. The DTacP-sIPV-Hib combination vaccine is safe and immunogenic in animal models. Three doses of the vaccine elicited satisfactory antibody responses in mice, rats, and cynomolgus monkeys.

Examining Routine Pediatric Vaccination Availability in Community Pharmacies in Washington State.

To address diminishing pediatric vaccination rates resulting from the COVID-19 pandemic, the Public Readiness and Emergency Preparedness (PREP) Act allows pharmacists, technicians, and pharmacy interns to administer any vaccine that the Advisory Committee on Immunization Practices (ACIP) guidelines recommend for all patients aged 3 years and older. A survey was conducted to evaluate the role of pharmacy personnel in the community setting providing immunizations for the pediatric patients. Sixty-seven pharmacies were contacted in a state where pharmacists are allowed to administer vaccinations to any patient over the age of six months. Of the 58 respondent pharmacies offering vaccinations for pediatric patients, the most commonly reported vaccines included influenza (97%), tetanus, diphtheria, and pertussis (88%), hepatitis (71%), human papillomavirus (69%), meningococcal vaccines (66%), polio (45%), and Haemophilus influenzae type b vaccine (40%). Nearly all respondent pharmacies (56/58) reported having at least one of the ACIP-recommended routine childhood vaccinations available for patients under the age of 18. Community pharmacies are well-positioned to administer routine vaccinations to pediatric patients and address declining pediatric vaccination rates.

Maternal Postnatal Depression and Completion of Infant Immunizations: A UK Cohort Study of 196,329 Mother-Infant Pairs, 2006-2015.

Objective: To examine the relationship between maternal postnatal depression and completion of infant vaccinations.Methods: We conducted a cohort study using data from The Health Improvement Network (THIN), a large UK primary care electronic health record database. We identified 196,329 mother-infant pairs in which the infant was born between 2006 and 2015. Postnatal depression was identified through antidepressant prescriptions or diagnoses or symptoms of depression in first year after childbirth. Primary outcome was completion of three 5-in-1 vaccination doses in infants before 1 year of age; this vaccine protects against diphtheria, tetanus, whooping cough, polio, and Haemophilus influenzae type b. We used Poisson regression models to compare likelihood of infant 5-in-1 vaccine uptake among children of women with a record of postnatal depression to likelihood among those without.Results: Of the 196,329 women, 20,802 (10.6%) had a record of postnatal depression and/or antidepressant prescription. There was no difference in infants' 5-in-1 vaccination completion between those of mothers with a record and those of mothers' without (adjusted incidence rate ratio [IRR] = 1.01; 95% CI, 0.99-1.02). Those from more socially deprived areas were less likely to complete infant vaccinations compared to those from the least deprived areas (IRR = 0.92; 95% CI, 0.90-0.93). Likelihood of completing infant vaccination decreased over time, comparing 2014-2015 to 2006-2007 (IRR = 0.90; 95% CI, 0.89-0.92).Conclusions: Among mothers who engage with primary care, maternal postnatal depression is not associated with lower rates of infant vaccination, though more research is needed to conclude if either more severe depression or unrecognized depression is associated with lower completion rates.

Immunogenicity of a Candidate DTacP-sIPV Combined Vaccine and Its Protection Efficacy against Pertussis in a Rhesus Macaque Model.

The research and development of a pertussis-combined vaccine using a novel inactivated poliovirus vaccine made from the Sabin strain (sIPV) is of great significance in the polio eradication project and to address the recent resurge in pertussis. In the present study, we compared the immunogenicity and efficacy of a candidate DTacP-sIPV with those of a commercial DTacP-wIPV/Hib, DTaP/Hib, pertussis vaccine, and aluminum hydroxide adjuvant control in the rhesus macaque model with a 0-, 1-, and 2-month immunization schedule. At day 28 after the third dose, rhesus macaques were challenged with aerosol pertussis and the antibody and cellular response together with pertussis clinical symptoms were determined. The production of anti-PT, anti-PRN, anti-FHA, anti-DT, anti-TT, and polio type I, II, III antibodies was induced by the candidate DTacP-sIPV, which was as potent as commercial vaccines. In comparison with the control group that showed typical pertussis symptoms of humans after the aerosol challenge, the DTacP-sIPV group did not exhibit obvious clinical pertussis symptoms and had higher neutralization titers of anti-PT, anti-PRN, and anti-FHA. In conclusion, the DTacP-sIPV vaccine was able to induce immunity in rhesus macaques to prevent pertussis infections after immunization. The developed vaccine was as efficient as other commercial vaccines.

A National Cross-Sectional Study from the Republic of Kosovo on Lot Quality Assurance Sampling (LQAS) to Evaluate the Vaccination Status of Children Between 12 and 24 Months of Age During 2018 to 2020

BackgroundIn the Republic of Kosovo, full vaccination status in children under age 2 years includes: 1 dose of Bacillus Calmette-Guérin (BCG) hepatitis B virus (HBV) vaccine; 3 doses of diphtheria, tetanus, pertussis, hepatitis B, polio, and Haemophilus influenzae type b (DTaP-HB-IPV-Hib) vaccine; 3 doses of inactivated polio vaccine (IPV); and 1 dose of measles, mumps, and rubella (MMR) vaccine. Lot quality assurance sampling (LQAS) is a method used to assess the performance of health quality indicators.Material/MethodsA national cross-sectional study with children aged between 12 and 24 months from Kosovo was performed between 2018 and 2020. The vaccination status of children was assessed with lot quality assurance sampling (LQAS) using randomized samples.ResultsAmong 430 children, more than 90% had completed the full immunization schedule. Delays in children’s immunizations were observed. Most vaccinations showed short delays of less than 1 month, followed by delays of up to 3 months. The main reason for vaccination delay was the COVID-19 pandemic, following by child’s illness at the scheduled time of vaccination or the parents were too busy to take the child to the vaccination site. Meanwhile, child age was the only parameter that showed difference among non-vaccinated and fully vaccinated (P<0.001).ConclusionsLQAS analysis showed that between 2018 and 2020 lack of full immunization was due to delay caused by the parent not taking the child to the vaccination site, which may be prevented by improving information given to parents and the use of vaccination reminders.

Intradermal administration of fractional doses of the inactivated poliovirus vaccine in a campaign: a pragmatic, open-label, non-inferiority trial in The Gambia

SummaryBackgroundA rapid increase in circulating vaccine-derived poliovirus type 2 outbreaks, and the need to reserve inactivated poliovirus vaccine (IPV) for routine immunisation, has increased the value of fractional dose IPV (fIPV) as a measure to prevent acute flaccid paralysis. However, the intradermal route of administration has been viewed as prohibitive to outbreak response campaigns. We aimed to establish the immunogenicity and safety of administering intradermal fIPV with a disposable syringe jet injector (DSJI) or an intradermal adaptor (IDA) compared with standard administration with a BCG needle and syringe (N&S).MethodsThis pragmatic, non-inferiority trial was undertaken in a campaign setting in communities in The Gambia. Children aged 4–59 months without contraindication to vaccination were eligible. Children were not individually randomly assigned; instead, the vaccination teams were randomly assigned (1:1:1) to one of three administration methods. Parents and the field team were not masked, but laboratory personnel were masked. Baseline demographic and anthropometric data were collected from the participants. Public health officers experienced at intradermal immunisation, and nurses without experience, had 2 h of training on each of the administration methods before the campaign. Participants were vaccinated using the administration method in use by the vaccination team in their community. Poliovirus serum neutralising antibodies (SNA) were measured in children aged 24–59 months before and 4 weeks after vaccination. Adverse events and data on injection quality were collected from all participants. The primary outcome was the type 2 immune response rate (seroconversion in seronegative [SNA titre <8] children plus a 4-fold titre rise in seropositive children). Adjusted differences in the immune response between the DSJI or IDA group versus the N&S group were calculated with 97·5% CIs. A margin of −10% was used to define the non-inferiority of DSJI or IDA compared to N&S. Immunogenicity analysis was done per protocol. The trial is registered with ClinicalTrials.govNCT02967783 and has been completed.FindingsBetween Oct 28 and Dec 29, 2016, 3189 children aged 4–59 months were recruited, of whom 3170 were eligible. Over 3 days, 2720 children were vaccinated (N&S, 917; IDA, 874; and DSJI, 929). Among 992 children aged 25–59 months with a baseline SNA available, 90·1% (95% CI 86·1–92·9; 281/312) of those vaccinated using the DSJI had an immune response to type 2 compared with 93·8% (90·6–95·8; 331/353) of those vaccinated with N&S and 96·6% (94·0–98·0; 316/327) of those vaccinated with IDA. All (53/53) type 2 seronegative children seroconverted. For polio type 2, non-inferiority was shown for both the IDA (adjusted difference 0·7% [97·5% CI −3·3 to 4·7], unadjusted difference 2·9% [–0·9 to 6·8]) and DSJI (adjusted difference −3·3% [–8·3 to 1·5], unadjusted difference −3·7% [–8·7 to 1·1]) compared with N&S. Non-inferiority was shown for type 1 and 3 for the IDA and DSJI. Neither injection quality nor the training and experience of the vaccinators had an effect on immune response. No safety concerns were reported.InterpretationIn a campaign, intradermal fIPV is safe and generates consistent immune responses that are not dependent on vaccinator experience or injection quality when administered using an N&S, DSJI, or IDA. Countries facing vaccine-derived poliovirus type 2 outbreaks should consider fIPV campaigns to boost population immunity and prevent cases of acute flaccid paralysis.FundingWorld Health Organization and the Medical Research Council.

Quercitin as an antiviral weapon-A review

Antioxidants are substances that can prevent cells from the damage caused by unstable molecules such as free radicals. Quercetin, a plant pigment present in many fruits, vegetables, grains, and one of the most beneficial antioxidants in the diet and plays an important role in helping the body and prevent free radical damage, which is linked to chronic diseases. The antioxidant properties of quercetin may help to reduce inflammation, allergy symptoms, blood pressure. A lot of studies have been done and experiments have been conducted both in vivo and in vitro and it has been found that in cultured cells many respiratory viruses were inhibited by quercetin. At a minimal inhibitory concentration of 0.03 to 0.5μg/ml in WI-38 or Hela cells, Cytopathic effects produced by echovirus type 7,11,12,19, rhinovirus, poliovirus, and coxsackievirus A21 and B1 were inhibited. The plaque formed by DNA and RNA viruses such as Herpes Simplex Virus-1, Polio type 1, and parainfluenza types 3 were effectively reduced demonstrating its anti-replicative properties. This article reviews effect of quercetin on different types of viral infections.

Immunogenicity of Viral Vaccines in the Italian Military.

Military personnel of all armed forces receive multiple vaccinations and have been doing so since long ago, but relatively few studies have investigated the possible negative or positive interference of simultaneous vaccinations. As a contribution to fill this gap, we analyzed the response to the live trivalent measles/mumps/rubella (MMR), the inactivated hepatitis A virus (HAV), the inactivated trivalent polio, and the trivalent subunits influenza vaccines in two cohorts of Italian military personnel. The first cohort was represented by 108 students from military schools and the second by 72 soldiers engaged in a nine-month mission abroad. MMR and HAV vaccines had never been administered before, whereas inactivated polio was administered to adults primed at infancy with a live trivalent oral polio vaccine. Accordingly, nearly all subjects had baseline antibodies to polio types 1 and 3, but unexpectedly, anti-measles/-mumps/-rubella antibodies were present in 82%, 82%, and 73.5% of subjects, respectively (43% for all of the antigens). Finally, anti-HAV antibodies were detectable in 14% and anti-influenza (H1/H3/B) in 18% of the study population. At mine months post-vaccination, 92% of subjects had protective antibody levels for all MMR antigens, 96% for HAV, 69% for the three influenza antigens, and 100% for polio types 1 and 3. An inverse relationship between baseline and post-vaccination antibody levels was noticed with all the vaccines. An excellent vaccine immunogenicity, a calculated long antibody persistence, and apparent lack of vaccine interference were observed.

Getting to Normal Will Require Better Testing, Vaccination, and Communication

Getting to Normal Will Require Better Testing, Vaccination, and Communication

Immunogenicity and safety of an adjuvanted inactivated polio vaccine, IPV-Al, in primary and booster trials in Asia, Central America and Europe

Background: Withdrawal of OPV and the widespread introduction of IPV is key in the Polio Endgame Strategy. This transition from OPV to IPV requires more and affordable IPV in quantities sufficient to secure at least two doses of IPV for every child. An adjuvanted inactivated polio vaccine (IPV-Al), obtained by adsorption of a reduced dose of inactivated poliovirus to an aluminium hydroxide adjuvant, can help mitigate global supply and cost constraints of IPV through dose-sparing. Aim: Investigation of immunogenicity and safety of IPV-Al compared to standard IPV: Methods and materials: Two primary vaccination phase 3 trials in infants vaccinated at 6, 10, 14 weeks and 9 months in the Philippines; at 2, 4, 6 months and 15–18 months in Panama. A Phase 2 primary vaccination trial in the Dominican Republic in infants vaccinated at 6, 10, 14 weeks. A Phase 1/2 booster vaccination trial in Denmark in children and adolescents (10–15 years) with a history of standard IPV vaccination. Results: Seroconversion rates (an antibody titre ≥4-fold higher than the estimated maternal antibody titre and a titre ≥8) evaluated one month after primary vaccination were: polio type 1, 96–98% (IPV-Al) versus 99–100% (IPV); type 2, 94–100% versus 99–100%; and type 3, 98–99% versus 99–100%. Non-inferiority of IPV-Al to IPV (predefined 10%-point margin) was confirmed in trials assessing primary immunogenicity. In infants, robust booster responses were demonstrated following a fourth polio vaccination and post-booster geometric mean titres (GMTs) were higher than post-priming GMTs. In the adolescent trial, robust booster responses were demonstrated following a fifth polio vaccination. IPV-Al was well tolerated with a safety profile comparable to that of standard IPV in the three trials. Conclusion: IPV-Al was demonstrated to be non-inferior to standard IPV for seroconversion following primary vaccination in the EPI schedule in Philippines and Dominican Republic, and at 2, 4, 6 months in Panama. Robust post-booster responses in 9-month-olds, 15–18-month-olds and 10–15-year-olds were demonstrated for IPV-Al. IPV-Al was safe and well tolerated. Results support the applicability of the dose-sparing adjuvanted IPV-Al vaccine to help secure a more affordable and stable supply of IPV for prevention of poliomyelitis as part of the global polio eradication initiative.

Timeliness of DTaP-IPV-Hib Vaccination and Development of Atopic Dermatitis Between 4 Months and 1 Year of Age—Register-Based Cohort Study

An Australian study including 4433 children found that delayed Diphtheria-Tetanus-acellular Pertussis-containing vaccination was associated with reduced risk of developing atopic dermatitis (AD) before age 1 year. We assessed whether delayed vaccination against diphtheria, tetanus, acellular pertussis, polio, and Haemophilus influenzae type b (Diphtheria, Tetanus, acellular Pertussis - Inactivated Polio vaccine - Haemophilus influenzae type b [DTaP]) was associated with a reduced risk of new cases of AD before age 1 year in Denmark. We used nationwide registers to follow 883,160 children born in Denmark from 1997 to 2012. Binary regression models adjusting for potential confounding factors were applied to estimate relative risks (adjusted relative risks [aRRs]) of developing AD among children with delayed DTaP vaccination (defined as given 1 month or more after the recommended age) compared with timely vaccinated children. Among 143,429 children with a delayed first dose of DTaP, 4,847 (3.4%) developed AD between age 4 months and 1 year, compared with 27,628 (3.7%) among 739,731 children not having delayed DTaP (aRR 0.94; 95% CI, 0.91-0.97). The aRR was 0.94 (95% CI, 0.90-0.99) for children with a delayed second dose, and the aRR was 0.88 (95% CI, 0.82-0.93) when comparing children with delayed first and second doses with all timely vaccinated children. The results support the hypothesis that delayed vaccination with DTaP is associated with reduced risk of developing new cases of AD after age 4 months. The dose-dependent relationship strengthens the evidence of a causal relationship. Some countries are introducing maternal pertussis vaccination and delaying the first dose of DTaP, providing a possibility for further testing the hypothesis.

The second coming: The comeback of the live vaccines.

Live vaccines are gradually replaced by protein-based vaccines given the latter's better safety. But live vaccines seem to be more efficient via stimulation of the innate immune system.

Influence of gut microbiota on mucosal IgA antibody response to the polio vaccine

The impact of intestinal microbiota on mucosal antibody response to the polio vaccine is poorly understood. We examined changes in vaccine-induced intestinal mucosal immunity to poliovirus by measuring the immunoglobulin A (IgA) antibody levels in stool samples collected from 107 infants in China, and the samples were collected 14 days after different sequential vaccinations combining inactivated polio vaccine (IPV) with oral poliovirus vaccine (OPV). Gut microbiota were identified using 16S ribosomal RNA sequencing 28 days before, 14 days before, and at the last dose of OPV. Vaccine-induced type 2-specific mucosal IgA showed a decrease after switching from trivalent to bivalent OPV (bOPV) (positive rate of polio type 2-specific mucosal IgA, 16.7%, 11.8%, and 45.9% for IPV + 2bOPV, 2IPV + bOPV, and 2IPV + trivalent OPV groups, respectively). The composition of the gut microbiome was significantly different, a higher abundance of Firmicutes and a lower abundance of Actinobacteria were observed in IgA-negative infant (n = 66) compared with IgA-positive infants (n = 39), and the gut microbiota were more diverse in IgA-negative infants on the day of OPV inoculation. The abundance of Clostridia was concomitant with a significantly lower conversion rate of mucosal IgA responses to the polio vaccine. The composition of the gut microbiome may affect the intestinal mucosal IgA response to the polio vaccine.