Publications by authors named "Pierre Van Damme"

302 Publications

Triage of human papillomavirus infected women by methylation analysis in first-void urine.

Sci Rep 2021 Apr 12;11(1):7862. Epub 2021 Apr 12.

Centre for the Evaluation of Vaccination (CEV), Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Campus Drie Eiken, Building S2, Universiteitsplein 1, 2610, Wilrijk, Belgium.

Host cell DNA methylation analysis in urine provides promising triage markers for women diagnosed with a high-risk (HR) human papillomavirus (HPV) infection. In this study, we have investigated a panel of six host cell methylation markers (GHSR, SST, ZIC1, ASCL1, LHX8, ST6GALNAC5) in cervicovaginal secretions collected within the first part of the urine void (FVU) from a referral population. Cytology, histology, and HPV DNA genotyping results on paired FVU and cervical samples were available. Urinary median methylation levels from HR-HPV (n = 93) positive women were found to increase for all markers with severity of underlying disease. Significantly elevated levels were observed for GHSR and LHX8 in relation to high-grade cervical intraepithelial neoplasia (CIN2 +; n = 33), with area under de curve values of 0.80 (95% Confidence Interval (CI) 0.59-0.92) and 0.76 (95% CI 0.58-0.89), respectively. These findings are the first to support the assertion that methylation analysis of host cell genes is feasible in FVU and holds promise as molecular, triage strategy to discern low- from high-grade cervical disease in HR-HPV positive women. Molecular testing on FVU may serve to increase cervical cancer screening attendance in hard-to-reach populations whilst reducing loss to follow-up and await further optimization and validation studies.
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http://dx.doi.org/10.1038/s41598-021-87329-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042010PMC
April 2021

The influenza vaccine for nursing and care professionals at emergency services in Flanders.

Hum Vaccin Immunother 2021 Apr 12:1-4. Epub 2021 Apr 12.

University of Antwerp, Faculty of Medicine and Health Sciences, Master of Nursing and Midwifery, Campus Drie Eiken, Wilrijk, Belgium.

: The Belgian Superior Health Council recommends seasonal influenza vaccination for people working in the health care sector in order to reduce the risk of the influenza virus being transmitted to people at risk. The aim of this study is to provide more insight into the current vaccination rate in nurses and health care professionals in emergency services in Flanders. In addition, the influence of influenza vaccination on absenteeism will be investigated, as well as the motivation to get vaccinated or not.: A quantitative multicentre, cross-sectional study was carried out in whichnurses and health care professionals in emergency services in Flanders were questioned by means of an online questionnaire.: The survey of nurses and health care professionals in Flanders from 2018 shows that 54% (294/548) gets vaccinated in this year. Respondents who have been vaccinated report a lower absenteeism due to influenza compared to health workers who do not get vaccinated. There is a lack of general knowledge about influenza and vaccination. Thirty-four percent of nurses and health care professionals in emergencies do not know the correct definition of influenza. The main reasons for being vaccinated are: to protect oneself (27%), family members (21.5%) and patients (16%). Reasons for not getting vaccinated are: never having had the influenza before (30%), believing you get the influenza because of the vaccination (12%), no belief or trust in the vaccine (19%). Three percent of respondents who received the influenza vaccine were absent due to flu. The absence due to influenza was higher among the respondents who were not vaccinated, namely 11%. Being vaccinated for influenza or not has been associated with being absent for influenza.: Given that there is a lack of general knowledge about influenza and its vaccination, the vaccination campaigns should cover this knowledge gap. Efforts to convince both nursing and care professionals about the protective role of the Influenza vaccine. These efforts can improve the influenza vaccination coverage rate and consequently minimize the absenteeism.: WHO: World Health Organization; UZA: University Hospital of Antwerp; SPSS: Statistical Package for the Social Sciences.
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http://dx.doi.org/10.1080/21645515.2021.1894062DOI Listing
April 2021

Breast milk antibody levels in Tdap vaccinated women after preterm delivery.

Clin Infect Dis 2021 Mar 26. Epub 2021 Mar 26.

Centre for the Evaluation of Vaccination (CEV); Vaccine & Infectious Diseases Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium.

Introduction/background & Aims: Enrichment of breast milk (BM) with immunoglobin (Ig)A and IgG, through maternal vaccination, could help young infants combat targeted pathogens. However, evidence on this effect after preterm delivery is lacking. This study investigated the total and anti-pertussis toxin (anti-PT) specific IgA and IgG production in BM after term or preterm delivery in the presence of maternal Tdap (tetanus, diphtheria, acellular pertussis) vaccination.

Methods: Serum and BM samples of lactating women, who delivered at term or prematurely and did or did not receive Tdap vaccine (Boostrix®, GSK Biologicals) during pregnancy, were collected as part of a clinical study (N=234, NCT02511327). Anti-PT IgA/IgG (IBL®; MSD®) and Total IgA/IgG (Thermofisher®, on BM samples only) immunosorbent assays were performed on all samples collected at 72 hours, 4, 8, and 12 weeks postpartum.

Results: BM after preterm delivery contained anti-PT IgA and IgG geometric mean concentrations (GMCs) comparable to those after term delivery (e.g. colostrum anti-PT IgA: 5.39 International Units per milliliter (IU/mL) vs 6.69 IU/mL, respectively). Maternal Tdap vaccination induced significantly higher anti-PT IgG GMC's in colostrum of vaccinated compared to unvaccinated women delivering at term (0.110 IU/mL vs 0.027 IU/mL, p=0.009). Compliance with postpartum vaccination led to no differences in BM after 4 weeks postpartum. Anti-PT antibodies persisted up to 12 weeks postpartum.

Conclusions: This study provides evidence that maternal Tdap vaccination induces high Ig levels in BM after both term and preterm delivery and that these antibodies remain abundantly present throughout lactation, possibly offering additional mucosal protection during the most vulnerable period in early life.
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http://dx.doi.org/10.1093/cid/ciab260DOI Listing
March 2021

Immunogenicity and safety of a nine-valent human papillomavirus vaccine in women 27-45 years of age compared to women 16-26 years of age: An open-label phase 3 study.

Vaccine 2021 Mar 3. Epub 2021 Mar 3.

Merck & Co., Inc., Kenilworth, NJ, USA. Electronic address:

Background: Efficacy of the nine-valent human papillomavirus (9vHPV; HPV types 6/11/16/18/31/33/45/52/58) vaccine was demonstrated in a phase 3 study in women 16-26 years of age. We present a phase 3 immunogenicity and safety study of the 9vHPV vaccine in women 27-45 versus 16-26 years of age.

Methods: This international, open-label study (NCT03158220) was conducted in women 16-45 years of age. Participants (16-26 years, n = 570 and 27-45 years, n = 642) received a three-dose 9vHPV vaccination regimen (day 1, month 2, month 6). Month 7 geometric mean titers (GMTs) and seroconversion percentages to anti-HPV 6/11/16/18/31/33/45/52/58 were assessed. Participants were followed for safety throughout the study.

Results: At month 7, anti-HPV 6/11/16/18/31/33/45/52/58 GMTs in women 27-45 years were compared to those in women 16-26 years of age. The primary hypothesis of non-inferiority of anti-HPV 16/18/31/33/45/52/58 GMTs in older versus younger women was met. The lower bound of the GMT ratio 95% confidence interval (27-45 years to 16-26 years) was 0.60-0.67 depending on HPV type, exceeding the non-inferiority margin of 0.5 for all HPV types. Month 7 seroconversion percentages in women 27-45 years of age were >99% for all HPV types. Injection-site and vaccine-related systemic adverse events (AEs) were observed in 87.5% and 25.1% of women 16-26 years, and 85.2% and 24.1% of women 27-45 years of age, respectively; no vaccine-related serious AEs were reported and no deaths occurred during the study.

Conclusions: The 9vHPV vaccine elicited non-inferior anti-HPV GMTs in women 27-45 years compared with women 16-26 years of age for HPV 16/18/31/33/45/52/58. The vaccine was generally well tolerated with a similar AE profile across the age groups. These data support bridging 9vHPV vaccine efficacy findings in women 16-26 years to women 27-45 years of age. Clinical trial registration NCT03158220.
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http://dx.doi.org/10.1016/j.vaccine.2021.01.074DOI Listing
March 2021

One or two doses of hepatitis A vaccine in universal vaccination programs in children in 2020: A systematic review.

Vaccine 2021 Jan 29. Epub 2021 Jan 29.

GSK, 20 Fleming Avenue, 1300 Wavre, Belgium. Electronic address:

Background: Hepatitis A virus (HAV) is a global health concern as outbreaks continue to occur. Since 1999, several countries have introduced universal vaccination (UV) of children against HAV according to approved two-dose schedules. Other countries have implemented one-dose UV programs since 2005; the long-term impact of this schedule is not yet known.

Methods: We conducted a systematic literature search in four electronic databases for data published between January 2000 and July 2019 to assess evidence for one-dose and two-dose UV of children with non-live HAV vaccines and describe their global impact on incidence, mortality, and severity of hepatitis A, vaccine effectiveness, vaccine efficacy, and antibody persistence.

Results: Of 3739 records screened, 33 peer-reviewed articles and one conference abstract were included. Rapid declines in incidence of hepatitis A and related outcomes were observed in all age groups post-introduction of UV programs, which persisted for at least 14 years for two-dose and six years for one-dose programs according to respective study durations. Vaccine effectiveness was ≥95% over 3-5 years for two-dose programs. Vaccine efficacy was >98% over 0.1-7.5 years for one-dose vaccination. Antibody persistence in vaccinated individuals was documented for up to 15 years (≥90%) and ten years (≥74%) for two-dose and one-dose schedules, respectively.

Conclusion: Experience with two-dose UV of children against HAV is extensive, demonstrating an impact on the incidence of hepatitis A and antibody persistence for at least 15 years in many countries globally. Because evidence is more limited for one-dose UV, we were unable to draw conclusions on immune response persistence beyond ten years or the need for booster doses later in life. Ongoing epidemiological monitoring is essential in countries implementing one-dose UV against HAV. Based on current evidence, two doses of non-live HAV vaccines are needed to ensure long-term protection.
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http://dx.doi.org/10.1016/j.vaccine.2021.01.038DOI Listing
January 2021

The Fifth International Neonatal and Maternal Immunization Symposium (INMIS 2019): Securing Protection for the Next Generation.

mSphere 2021 01 27;6(1). Epub 2021 Jan 27.

Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.

Despite significant progress in reaching some milestones of the United Nations Sustainable Development Goals, neonatal and early infant morbidity and mortality remain high, and maternal health remains suboptimal in many countries. Novel and improved preventative strategies with the potential to benefit pregnant women and their infants are needed, with maternal and neonatal immunization representing effective approaches. Experts from immunology, vaccinology, infectious diseases, clinicians, industry, public health, and vaccine-related social sciences convened at the 5th International Neonatal and Maternal Immunization Symposium (INMIS) in Vancouver, Canada, from 15 to 17 September 2019. We critically evaluated the lessons learned from recent clinical studies, presented cutting-edge scientific progress in maternal and neonatal immunology and vaccine development, and discussed maternal and neonatal immunization in the broader context of infectious disease epidemiology and public health. Focusing on practical aspects of research and implementation, we also discussed the safety, awareness, and perception of maternal immunization as an existing strategy to address the need to improve maternal and neonatal health worldwide. The symposium provided a comprehensive scientific and practical primer as well as an update for all those with an interest in maternal and neonatal infection, immunity, and vaccination. The summary presented here provides an update of the current status of progress in maternal and neonatal immunization.
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http://dx.doi.org/10.1128/mSphere.00862-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885317PMC
January 2021

Hospital-wide SARS-CoV-2 antibody screening of staff in a university psychiatric centre in Belgium.

BJPsych Open 2021 Jan 20;7(1):e40. Epub 2021 Jan 20.

Collaborative Antwerp Psychiatric Research Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Belgium; and Department of Psychiatry, University Psychiatric Hospital Campus Duffel, Belgium.

In this first serosurvey among psychiatric healthcare providers, only 3.2% of a sample of 431 staff members of a Belgian University Psychiatric Centre, screened 3-17 June 2020, had SARS-CoV-2 immunoglobulin G antibodies, which is considerably lower compared with both the general population and other healthcare workers in Belgium. The low seroprevalence was unexpected, given the limited availability of personal protective equipment and the high amount of COVID-19 symptoms reported by staff members. Importantly, exposure at home predicted the presence of antibodies, but exposure at work did not. Measures to prevent transmission from staff to patients are warranted in psychiatric facilities.
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http://dx.doi.org/10.1192/bjo.2020.172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844164PMC
January 2021

Interim Results of a Phase 1-2a Trial of Ad26.COV2.S Covid-19 Vaccine.

N Engl J Med 2021 Jan 13. Epub 2021 Jan 13.

From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, M.L.G., G. Shukarev, A.M.G., J. Stoop, S.T., E.C., G. Scheper, J. Hendriks, M.D., J.V.H., H.S.); Janssen Research and Development, Beerse (D.H., C.T., F.S.), Janssen Clinical Pharmacology Unit, Merksem (W.V.D.), the Center for Vaccinology, Ghent University, Gent (I.L.-R.), SGS Life Sciences (P.-J.B.) and the Center for the Evaluation of Vaccination, University of Antwerp (P.V.D.), Antwerp, and the Center for Clinical Pharmacology, University Hospitals Leuven, Leuven (J. de Hoon) - all in Belgium; Optimal Research, Melbourne, FL (M.K.); the Alliance for Multispecialty Research, Knoxville, TN (W.S.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (K.E.S., D.H.B.); and the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (S.C.D.R., K.W.C., M.J.M.).

Background: Efficacious vaccines are urgently needed to contain the ongoing coronavirus disease 2019 (Covid-19) pandemic of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A candidate vaccine, Ad26.COV2.S, is a recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike protein.

Methods: In this multicenter, placebo-controlled, phase 1-2a trial, we randomly assigned healthy adults between the ages of 18 and 55 years (cohort 1) and those 65 years of age or older (cohort 3) to receive the Ad26.COV2.S vaccine at a dose of 5×10 viral particles (low dose) or 1×10 viral particles (high dose) per milliliter or placebo in a single-dose or two-dose schedule. Longer-term data comparing a single-dose regimen with a two-dose regimen are being collected in cohort 2; those results are not reported here. The primary end points were the safety and reactogenicity of each dose schedule.

Results: After the administration of the first vaccine dose in 805 participants in cohorts 1 and 3 and after the second dose in cohort 1, the most frequent solicited adverse events were fatigue, headache, myalgia, and injection-site pain. The most frequent systemic adverse event was fever. Systemic adverse events were less common in cohort 3 than in cohort 1 and in those who received the low vaccine dose than in those who received the high dose. Reactogenicity was lower after the second dose. Neutralizing-antibody titers against wild-type virus were detected in 90% or more of all participants on day 29 after the first vaccine dose (geometric mean titer [GMT], 224 to 354) and reached 100% by day 57 with a further increase in titers (GMT, 288 to 488), regardless of vaccine dose or age group. Titers remained stable until at least day 71. A second dose provided an increase in the titer by a factor of 2.6 to 2.9 (GMT, 827 to 1266). Spike-binding antibody responses were similar to neutralizing-antibody responses. On day 14, CD4+ T-cell responses were detected in 76 to 83% of the participants in cohort 1 and in 60 to 67% of those in cohort 3, with a clear skewing toward type 1 helper T cells. CD8+ T-cell responses were robust overall but lower in cohort 3.

Conclusions: The safety and immunogenicity profiles of Ad26.COV2.S support further development of this vaccine candidate. (Funded by Johnson & Johnson and the Biomedical Advanced Research and Development Authority of the Department of Health and Human Services; COV1001 ClinicalTrials.gov number, NCT04436276.).
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http://dx.doi.org/10.1056/NEJMoa2034201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821985PMC
January 2021

Intestinal antibody responses to two novel live attenuated type 2 oral poliovirus vaccines in healthy adults in Belgium.

J Infect Dis 2020 Dec 24. Epub 2020 Dec 24.

Department of Pediatrics, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, United States of America.

In a blinded phase 1 trial (EudraCT 2017-0000908-21; NCT03430349) in Belgium, healthy adults (18 to 50 years) previously immunized exclusively with inactivated polio vaccine were administered a single dose of one of two novel type 2 oral polio vaccines (nOPV2-c1: S2/cre5/S15domV/rec1/hifi3 (N=15); nOPV2-c2: S2/S15domV/CpG40 (N=15)) and isolated for 28 days in a purpose-built containment facility. Using stool samples collected near days 0, 7, 14, and 28, we evaluated intestinal neutralization and IgA responses to the novel OPV2s and found that nOPV2-c1 and nOPV2-c2 induced detectable poliovirus type 2-specific intestinal neutralizing responses in 40.0% and 46.7% of participants respectively.
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http://dx.doi.org/10.1093/infdis/jiaa783DOI Listing
December 2020

Hepatitis A vaccination and its immunological and epidemiological long-term effects - a review of the evidence.

Hum Vaccin Immunother 2021 May 16;17(5):1496-1519. Epub 2020 Dec 16.

Centre for the Evaluation of Vaccination, Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.

Hepatitis A virus (HAV) infections continue to represent a significant disease burden causing approximately 200 million infections, 30 million symptomatic illnesses and 30,000 deaths each year. Effective and safe hepatitis A vaccines have been available since the early 1990s. Initially developed for individual prophylaxis, HAV vaccines are now increasingly used to control hepatitis A in endemic areas. The human enteral HAV is eradicable in principle, however, HAV eradication is currently not being pursued. Inactivated HAV vaccines are safe and, after two doses, elicit seroprotection in healthy children, adolescents, and young adults for an estimated 30-40 years, if not lifelong, with no need for a later second booster. The long-term effects of the single-dose live-attenuated HAV vaccines are less well documented but available data suggest they are safe and provide long-lasting immunity and protection. A universal mass vaccination strategy (UMV) based on two doses of inactivated vaccine is commonly implemented in endemic countries and eliminates clinical hepatitis A disease in toddlers within a few years. Consequently, older age groups also benefit due to the herd protection effects. Single-dose UMV programs have shown promising outcomes but need to be monitored for many more years in order to document an effective immune memory persistence. In non-endemic countries, prevention efforts need to focus on 'new' risk groups, such as men having sex with men, prisoners, the homeless, and families visiting friends and relatives in endemic countries. This narrative review presents the current evidence regarding the immunological and epidemiological long-term effects of the hepatitis A vaccination and finally discusses emerging issues and areas for research.
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http://dx.doi.org/10.1080/21645515.2020.1819742DOI Listing
May 2021

In-depth analysis of pneumococcal serotypes in Belgian children (2015-2018): Diversity, invasive disease potential, and antimicrobial susceptibility in carriage and disease.

Vaccine 2021 01 9;39(2):372-379. Epub 2020 Dec 9.

Centre for the Evaluation of Vaccination, Vaccine and Infectious Disease Institute, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, 2610 Wilrijk, Belgium.

Background: Changes in serotype distribution have been described after the switch from the 13-valent pneumococcal conjugate vaccine (PCV13) to the 10-valent pneumococcal conjugate vaccine (PCV10) in Belgium.

Aim: To describe serotype's invasive disease potential and the detailed evolution of serotype distribution and antimicrobial susceptibility of pneumococcal isolates (carriage and IPD) in children up to 30 months of age over a period during and after the vaccine switch (2015-2018).

Methods: S. pneumoniae strains isolated from the nasopharynx of healthy children attending day-care centres (DCCs) and strains from normally sterile sites of children with IPD were serotyped (Quellung-reaction) and antimicrobial susceptibility testing was performed. Invasive disease potential was defined as the serotype-specific odds ratio (OR).

Results: The highly invasive (OR > 1) serotypes 12F, 1, 3, 24A/B/F, 33F, 19A, and 9N were not frequently carried (<7.5% of carriage strains). Different serotypes dominated in carriage (23B, 23A, 11A, 15B) versus IPD (12F, 19A, 10A, 33F). PCV13 vaccine serotypes increased in carriage (5.4% (25/463) in period 1 vs 10.3% (69/668) in period 3) and in IPD (7.3% (8/110 in period 1 vs 23.9% (34/142) in period 3) due to an increase (p < 0.01) in serotype 19A. The penicillin non-susceptibility of 19A was lower (p = 0.02) in carriage (6.8%) than in IPD (23.5%). Erythromycin and tetracycline non-susceptibility were more frequent (p < 0.01) in IPD (26.0%; 23.0%) compared to carriage strains (18.2%; 14.5%) and penicillin non-susceptibility increased over the three year study period (carriage: 13.4%, 19.8%, 18.5%, p = 0.05; IPD: 11.8%, 15.0%, 20.4%, p = 0.02).

Conclusion: Only some of the serotypes with high invasive disease potential (serotype 1, 3, 19A) in Belgium are included in PCV10 and/or PCV13. This reinforces the need for continuous monitoring, both in healthy children as in children with IPD, to better understand the dynamics of pneumococcal disease, to optimise the composition and implementation of PCVs.
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http://dx.doi.org/10.1016/j.vaccine.2020.11.044DOI Listing
January 2021

Safety and immunogenicity of two novel type 2 oral poliovirus vaccine candidates compared with a monovalent type 2 oral poliovirus vaccine in healthy adults: two clinical trials.

Lancet 2021 Jan 9;397(10268):39-50. Epub 2020 Dec 9.

Centre for the Evaluation of Vaccination, Vaccine and Infectious Disease Institute, University of Antwerp, Wilrijk, Belgium. Electronic address:

Background: Two novel type 2 oral poliovirus vaccine (OPV2) candidates, novel OPV2-c1 and novel OPV2-c2, designed to be more genetically stable than the licensed Sabin monovalent OPV2, have been developed to respond to ongoing polio outbreaks due to circulating vaccine-derived type 2 polioviruses.

Methods: We did two randomised studies at two centres in Belgium. The first was a phase 4 historical control study of monovalent OPV2 in Antwerp, done before global withdrawal of OPV2, and the second was a phase 2 study in Antwerp and Ghent with novel OPV2-c1 and novel OPV2-c2. Eligible participants were healthy adults aged 18-50 years with documented history of at least three polio vaccinations, including OPV in the phase 4 study and either OPV or inactivated poliovirus vaccine (IPV) in the novel OPV2 phase 2 study, with no dose within 12 months of study start. In the historical control trial, participants were randomly assigned to either one dose or two doses of monovalent OPV2. In the novel OPV2 trial, participants with previous OPV vaccinations were randomly assigned to either one or two doses of novel OPV2-c1 or to one or two doses of novel OPV2-c2. IPV-vaccinated participants were randomly assigned to receive two doses of either novel OPV2-c1, novel OPV2-c2, or placebo. Vaccine administrators were unmasked to treatment; medical staff performing safety and reactogenicity assessments or blood draws for immunogenicity assessments were masked. Participants received the first vaccine dose on day 0, and a second dose on day 28 if assigned to receive a second dose. Primary objectives were assessments and comparisons of safety up to 28 days after each dose, including solicited adverse events and serious adverse events, and immunogenicity (seroprotection rates on day 28 after the first vaccine dose) between monovalent OPV2 and the two novel OPV2 candidates. Primary immunogenicity analyses were done in the per-protocol population. Safety was assessed in the total vaccinated population-ie, all participants who received at least one dose of their assigned vaccine. The phase 4 control study is registered with EudraCT (2015-003325-33) and the phase 2 novel OPV2 study is registered with EudraCT (2018-001684-22) and ClinicalTrials.gov (NCT04544787).

Findings: In the historical control study, between Jan 25 and March 18, 2016, 100 volunteers were enrolled and randomly assigned to receive one or two doses of monovalent OPV2 (n=50 in each group). In the novel OPV2 study, between Oct 15, 2018, and Feb 27, 2019, 200 previously OPV-vaccinated volunteers were assigned to the four groups to receive one or two doses of novel OPV2-c1 or novel OPV2-c2 (n=50 per group); a further 50 participants, previously vaccinated with IPV, were assigned to novel OPV2-c1 (n=17), novel OPV2-c2 (n=16), or placebo (n=17). All participants received the first dose of assigned vaccine or placebo and were included in the total vaccinated population. All vaccines appeared safe; no definitely vaccine-related withdrawals or serious adverse events were reported. After first doses in previously OPV-vaccinated participants, 62 (62%) of 100 monovalent OPV2 recipients, 71 (71%) of 100 recipients of novel OPV2-c1, and 74 (74%) of 100 recipients of novel OPV2-c2 reported solicited systemic adverse events, four (monovalent OPV2), three (novel OPV2-c1), and two (novel OPV2-c2) of which were considered severe. In IPV-vaccinated participants, solicited adverse events occurred in 16 (94%) of 17 who received novel OPV2-c1 (including one severe) and 13 (81%) of 16 who received novel OPV2-c2 (including one severe), compared with 15 (88%) of 17 placebo recipients (including two severe). In previously OPV-vaccinated participants, 286 (97%) of 296 were seropositive at baseline; after one dose, 100% of novel OPV2 vaccinees and 97 (97%) of monovalent OPV2 vaccinees were seropositive.

Interpretation: Novel OPV2 candidates were as safe, well tolerated, and immunogenic as monovalent OPV2 in previously OPV-vaccinated and IPV-vaccinated adults. These data supported the further assessment of the vaccine candidates in children and infants.

Funding: University of Antwerp and Bill & Melinda Gates Foundation.
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http://dx.doi.org/10.1016/S0140-6736(20)32541-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811203PMC
January 2021

Can COVID-19 symptoms as reported in a large-scale online survey be used to optimise spatial predictions of COVID-19 incidence risk in Belgium?

Spat Spatiotemporal Epidemiol 2020 11 25;35:100379. Epub 2020 Sep 25.

Center for Health Economics Research and Modeling Infectious Diseases, Vaccine and Infectious Disease Institute, University of Antwerp, Universiteitsplein 1, Antwerp 2610, Belgium.

Although COVID-19 has been spreading throughout Belgium since February, 2020, its spatial dynamics in Belgium remain poorly understood, partly due to the limited testing of suspected cases during the epidemic's early phase. We analyse data of COVID-19 symptoms, as self-reported in a weekly online survey, which is open to all Belgian citizens. We predict symptoms' incidence using binomial models for spatially discrete data, and we introduce these as a covariate in the spatial analysis of COVID-19 incidence, as reported by the Belgian government during the days following a survey round. The symptoms' incidence is moderately predictive of the variation in the relative risks based on the confirmed cases; exceedance probability maps of the symptoms' incidence and confirmed cases' relative risks overlap partly. We conclude that this framework can be used to detect COVID-19 clusters of substantial sizes, but it necessitates spatial information on finer scales to locate small clusters.
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http://dx.doi.org/10.1016/j.sste.2020.100379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518805PMC
November 2020

Infectious diseases epidemiology, quantitative methodology, and clinical research in the midst of the COVID-19 pandemic: Perspective from a European country.

Contemp Clin Trials 2020 12 22;99:106189. Epub 2020 Oct 22.

Belgian Health Care Knowledge Center (KCE), Belgium.

Starting from historic reflections, the current SARS-CoV-2 induced COVID-19 pandemic is examined from various perspectives, in terms of what it implies for the implementation of non-pharmaceutical interventions, the modeling and monitoring of the epidemic, the development of early-warning systems, the study of mortality, prevalence estimation, diagnostic and serological testing, vaccine development, and ultimately clinical trials. Emphasis is placed on how the pandemic had led to unprecedented speed in methodological and clinical development, the pitfalls thereof, but also the opportunities that it engenders for national and international collaboration, and how it has simplified and sped up procedures. We also study the impact of the pandemic on clinical trials in other indications. We note that it has placed biostatistics, epidemiology, virology, infectiology, and vaccinology, and related fields in the spotlight in an unprecedented way, implying great opportunities, but also the need to communicate effectively, often amidst controversy.
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http://dx.doi.org/10.1016/j.cct.2020.106189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581408PMC
December 2020

Elucidating the difference in the kinetics of antibody titres of infants in Belgium and Vietnam.

Vaccine 2020 10 12;38(45):7079-7086. Epub 2020 Sep 12.

I-Biostat, Data Science Institute, Hasselt University, Martelarenlaan 42, 3500 Hasselt, Belgium; Center for the Evaluation of Vaccination, Vaccine & Infectious Diseases Institute, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.

Serological results obtained in a single laboratory from twin-studies on maternal immunisation, in Vietnam and Belgium offer the opportunity to compare antibody kinetics in infants before and after infant vaccination in the presence of vaccine-induced maternal antibodies. Nonlinear mixed-effects models (NLMMs) making use of a hypothesised dynamic evolution that captures the change in antibody titres over time, were employed to model anti-PT and anti-Prn antibody dynamics. Our proposed modelling approach provided useful insight into understanding the differences in the infants' antibody kinetics in both countries since NLMMs offer the possibility of pooling all data in one analysis and incorporate relevant covariates of interest. In both controlled cohort studies, pregnant women were vaccinated with a tetanus, diphtheria, acellular pertussis (Tdap) vaccine (Boostrix®, Belgium; Adacel®, Vietnam), and children were followed before and after primary vaccination, and before and after booster vaccination (Infanrix hexa®). From our models, both anti-PRN and anti-PT antibody titres at birth of Vietnamese infants were significantly lower than those of Belgian infants born to vaccinated women groups. Even though the antibody titres in the cord at birth of Belgian infants were also higher than those of Vietnamese infants born to the control women groups, the difference was not significant. The significant difference between infants born to vaccinated women in the two countries was likely due to the use of different vaccine brands in pregnant women and the different vaccination histories of women in these two countries. Our analyses also suggested that the blunting effect was present during the primary immunisation but went away afterward for anti-PT data. In contrast, for anti-PRN antibodies, the blunting effect persisted after the primary vaccination and possibly went away after the booster dose. Countries should be aware of the regional situation in view of recommending maternal immunization.
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http://dx.doi.org/10.1016/j.vaccine.2020.09.003DOI Listing
October 2020

Levels of antibodies specific to diphtheria toxoid, tetanus toxoid, and Haemophilus influenzae type b in healthy children born to Tdap-vaccinated mothers.

Vaccine 2020 10 2;38(44):6914-6921. Epub 2020 Sep 2.

Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. Electronic address:

Introduction: Vaccination of pregnant women protects both women and their newborns against some infectious diseases. Thailand implemented tetanus toxoid (TT) vaccination of pregnant women in 1977, which was replaced by tetanus-diphtheria toxoid (dT) vaccination in 2005. The tetanus-diphtheria-acellular pertussis (Tdap) vaccine has been recommended for pregnant women at 27-36 weeks of gestation since 2012 in several countries. Data on antibody responses to diphtheria toxoid (DT), TT, and Hemophilus influenzae type b (Hib) induced by combined vaccines in children born to TT-vaccinated and/or Tdap-vaccinated mothers are limited.

Material And Methods: We investigated anti-DT, anti-TT, and anti-Hib IgG responses in a cohort of Thai children (ClinicalTrial.gov NCT02408926) born to mothers who received a TT-containing and/or the Tdap vaccine during pregnancy. Children born to Tdap-vaccinated mothers were randomized to receive either a hexavalent (Infanrix-hexa) or pentavalent (Quinvaxem) vaccine, whereas children born to TT-vaccinated mothers received only Quinvaxem vaccine at 2, 4, 6, and 18 months of age. IgG levels were evaluated at birth (cord blood), 2 (pre-primary), 7 (post-primary), 18 (pre-booster), and 19 months of age (post-booster) using a commercially available enzyme-linked immunoassay.

Results: Seroprotective concentrations of anti-DT, anti-TT, and anti-Hib IgG were achieved in >90% and >99% of children following primary and booster vaccination, respectively. Among children born to Tdap-vaccinated mothers, the pentavalent vaccine induced higher levels of anti-Hib IgG than the hexavalent vaccine after primary and booster vaccination. Significantly higher anti-Hib IgG levels were observed among children receiving the pentavalent vaccine and who were born to TT-vaccinated mothers than among children receiving the pentavalent vaccine and born to Tdap-vaccinated mothers after primary and booster vaccination.

Conclusions: Vaccination with a TT-containing and/or the Tdap vaccine during pregnancy did not compromise the seroprotection rate achieved following primary and booster immunization in individuals receiving either the pentavalent or hexavalent vaccine.
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http://dx.doi.org/10.1016/j.vaccine.2020.08.058DOI Listing
October 2020

Immunogenicity and persistence of trivalent measles, mumps, and rubella vaccines: a systematic review and meta-analysis.

Lancet Infect Dis 2021 02 1;21(2):286-295. Epub 2020 Sep 1.

Data Science Institute, I-BioStat, UHasselt, Diepenbeek, Belgium; Centre for Health Economic Research and Modelling Infectious Diseases, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.

Background: Despite the universal use of the two-dose trivalent measles-mumps-rubella (MMR) vaccine in the past two decades, outbreaks of these diseases still occur in countries with high vaccine uptake, giving rise to concerns about primary and secondary failure of MMR vaccine components. We aimed to provide seroconversion and waning rate estimates for the measles, mumps, and rubella components of MMR vaccines.

Methods: In this systematic review and meta-analysis we searched PubMed (including MEDLINE), Web of Science, and Embase for randomised controlled trials, cohort studies, or longitudinal studies reporting the immunogenicity and persistence of MMR vaccines, published in English from database inception to Dec 31, 2019. Studies were included if they investigated vaccine-induced immunity in healthy individuals who received a trivalent MMR vaccine, including different dosages and timepoints of vaccine administration. Studies featuring coadministration of MMR with other vaccines, maternal immunity to the MMR vaccine, or non-trivalent formulations of the vaccine were excluded. Pooled seroconversion and waning rates were estimated by random-effects meta-analyses. This study is registered with PROSPERO, CRD42019116705.

Findings: We identified 3615 unique studies, 62 (1·7%) of which were eligible for analysis. Estimated overall seroconversion rates were 96·0% (95% CI 94·5-97·4; I=91·1%) for measles, 93·3% (91·1-95·2; I=94·9%) for mumps when excluding the Rubini strain, 91·1% (87·4-94·1; I=96·6%) for mumps when including the Rubini strain, and 98·3% (97·3-99·2; I=93·0%) for rubella. Estimated overall annual waning rates were 0·009 (95% CI 0·005-0·016; I=85·2%) for measles, 0·024 (0·016-0·039; I=94·7%) for mumps, and 0·012 (0·010-0·014; I=93·3%) for rubella.

Interpretation: Our meta-analysis provides estimates of primary and secondary vaccine failure, which are essential to improve the accuracy of mathematical and statistical modelling to understand and predict the occurrence of future measles, mumps, and rubella outbreaks in countries with high vaccine uptake.

Funding: European Research Council.
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http://dx.doi.org/10.1016/S1473-3099(20)30442-4DOI Listing
February 2021

Non-invasive Assessment of Vaccine-Induced HPV Antibodies via First-Void Urine.

Front Immunol 2020 5;11:1657. Epub 2020 Aug 5.

Faculty of Medicine and Health Sciences, Centre for the Evaluation of Vaccination, Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium.

The potential of first-void (FV) urine as a non-invasive method to monitor human papillomavirus (HPV) vaccination has been reported, mainly focusing on urine as a sample to assess HPV DNA. Besides HPV DNA, vaccine-induced HPV antibodies originating from cervicovaginal secretions were recently shown to be detectable in FV urine as well. This presents a novel opportunity for non-invasive sampling to monitor HPV antibody status in women participating in large epidemiological studies and HPV vaccine trials. The simultaneous assessment of both HPV infection and immunogenicity on a non-invasive, readily obtained sample is particularly attractive.
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http://dx.doi.org/10.3389/fimmu.2020.01657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419594PMC
April 2021

Vaccines and routine immunization strategies during the COVID-19 pandemic.

Hum Vaccin Immunother 2021 Feb 26;17(2):400-407. Epub 2020 Aug 26.

Departments of Pediatrics and Molecular Virology and Microbiology, Baylor College of Medicine , Houston, TX, USA.

Severe acute respiratory syndrome coronavirus 2 related disease (COVID-19) is now responsible for one of the most challenging and concerning pandemics. By August 2020, there were almost 20 million confirmed cases worldwide and well over half-million deaths. Since there is still no effective treatment or vaccine, non-pharmaceutical interventions have been implemented in an attempt to contain the spread of the virus. During times of quarantine, immunization practices in all age groups, especially routine childhood vaccines, have also been interrupted, delayed, re-organized, or completely suspended. Numerous high-income as well as low- and middle-income countries are now experiencing a rapid decline in childhood immunization coverage rates. We will, inevitably, see serious consequences related to suboptimal control of vaccine-preventable diseases (VPDs) in children concurrent with or following the pandemic. Routine pediatric immunizations of individual children at clinics, mass vaccination campaigns, and surveillance for VPDs must continue as much as possible during pandemic.
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http://dx.doi.org/10.1080/21645515.2020.1804776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899627PMC
February 2021

Point-of-Care Tests for Hepatitis B Are Associated with A Higher Linkage to Care and Lower Cost Compared to Venepuncture Sampling During Outreach Screenings in an Asian Migrant Population.

Ann Glob Health 2020 07 16;86(1):81. Epub 2020 Jul 16.

Department of Gastroenterology and Hepatology, Antwerp University Hospital, Antwerp, BE.

Background: This study compares venepuncture versus point-of-care (POC) HBsAg tests on screening cost and linkage to care in prospective outreach screenings in an Asian population in three major cities in Belgium between 10/2014 and 5/2018.

Methods: Two community outreach screening programs were organised between 10/2014 and 5/2018. The first screening program used venepuncture and serologic testing for HBsAg. In the second program, HBsAg was tested in finger stick blood POC tests. Positive results were confirmed during outpatient visits with serologic testing. Linkage to care was defined as having received specialist care follow-up with at least one abdominal ultrasound within three months of screening.

Results: For 575 participating individuals, 571 valid results were obtained, 456 with venepuncture, and 115 using POC testing. Overall HBsAg seroprevalence was 6.8%. Linkage to care was higher when using POC testing compared to venepuncture (86% or n = 6/7 versus 34% or n = 11/32; p = 0.020). The POC screening program was economically more attractive with a total cost of € 1,461.8 or € 12.7 per person screened compared to € 24,819 or € 54.0 per person screened when using venepuncture testing. Results and an appointment for specialist care follow-up were given onsite with POC testing, while with venepuncture testing; results were sent within 20-45 days.

Conclusion: In an Asian migrant population in Belgium with an HBsAg seroprevalence of 6.8%, HBV screening based on POC tests resulted in lower costs per person screened (76.5% lower), and higher linkage to care (2.5 times).
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http://dx.doi.org/10.5334/aogh.2848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366862PMC
July 2020

Early detection of chronic hepatitis B and risk factor assessment in Turkish migrants, Middle Limburg, Belgium.

PLoS One 2020 27;15(7):e0234740. Epub 2020 Jul 27.

Department of Gastroenterology and Hepatology, Ziekenhuis Oost-Limburg, Genk, Belgium.

Background: Turkey is an intermediate hepatitis B virus (HBV) endemic country. However, prevalence among Turkish migrants in Belgium is unknown, especially in those born in Belgium with a foreign-born parent, i.e. second-generation migrants (SGM).

Aims: To evaluate the prevalence of HBV infection and associated risk factors in Turkish first-generation migrants (FGM), i.e. foreign-born, and SGM.

Methods: Between September 2017 and May 2019, free outreach testing for hepatitis B surface antigen (HBsAg), hepatitis B core antibodies (anti-HBc), and antibodies against HBsAg was offered to Turkish migrants in Middle-Limburg, Belgium. Face-to-face questionnaire assessed HBV risk factors. HBsAg positive patients were referred and followed up. Turkish SGM were stratified into birth cohort born before and after 1987, since those born after 1987 should be covered by the universal infant vaccination program.

Results: A total of 1,081/1,113 (97.1%) Turkish did go for HBV testing. Twenty-six (2.4%) were HBsAg positive; 11/26 were unaware of their status and 10/11 were successfully referred. HBsAg prevalence was 3.0% in FGM and 1.5% in SGM, p = .070. Only one out of seven HBsAg positive SGM was born after 1987. In the multiple generalized estimating equations model, the most important risk factors for anti-HBc positivity were male gender (p = .021), older age (p < .001), FGM (p < .001), low educational level of the mother (p = .003), HBV infected mother (p = .008), HBV infected siblings (p = .002), HBV infected other family member (p = .004), gynaecological examination in Turkey or unsafe male circumcision (p = .032) and dental treatment in Turkey (p = .049).

Conclusion: Outreach testing was well-accepted and referral to specialist care was generally successful. National HBV screening should be implemented in the Turkish FGM population and might be considered in SGM not covered by primary prevention strategies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0234740PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384618PMC
September 2020

'Alternative abridged preventive regimens against rabies for children in high endemic countries'.

Vaccine 2020 07;38(35):5578-5579

Department of Clinical Sciences, Institute of Tropical Medicine, Nationalestraat 155, 2000 Antwerp, Belgium.

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http://dx.doi.org/10.1016/j.vaccine.2020.06.029DOI Listing
July 2020

Global Perspectives on Immunization During Pregnancy and Priorities for Future Research and Development: An International Consensus Statement.

Front Immunol 2020 24;11:1282. Epub 2020 Jun 24.

Department of Medicine and Surgery, Pediatric Clinic, Pietro Barilla Children's Hospital, University of Parma, Parma, Italy.

Immunization during pregnancy has been recommended in an increasing number of countries. The aim of this strategy is to protect pregnant women and infants from severe infectious disease, morbidity and mortality and is currently limited to tetanus, inactivated influenza, and pertussis-containing vaccines. There have been recent advancements in the development of vaccines designed primarily for use in pregnant women (respiratory syncytial virus and group B vaccines). Although there is increasing evidence to support vaccination in pregnancy, important gaps in knowledge still exist and need to be addressed by future studies. This collaborative consensus paper provides a review of the current literature on immunization during pregnancy and highlights the gaps in knowledge and a consensus of priorities for future research initiatives, in order to optimize protection for both the mother and the infant.
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http://dx.doi.org/10.3389/fimmu.2020.01282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326941PMC
April 2021

Long-term immunogenicity, effectiveness, and safety of nine-valent human papillomavirus vaccine in girls and boys 9 to 15 years of age: Interim analysis after 8 years of follow-up.

Papillomavirus Res 2020 12 11;10:100203. Epub 2020 Jul 11.

Merck & Co., Inc., Kenilworth, NJ, USA. Electronic address:

Background: The nine-valent human papillomavirus (9vHPV) vaccine protects against infection and disease related to HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58. The pivotal 36-month Phase III immunogenicity study of 9vHPV vaccine in 9- to 15-year-old girls and boys was extended to assess long-term immunogenicity and effectiveness through approximately 10 years after vaccination. We describe results of an interim analysis based on approximately 8 years of follow-up after vaccination.

Methods: Participants aged 9-15 years who received three doses of 9vHPV vaccine (at day 1, month 2, and month 6) in the base study and consented to follow-up were enrolled in the long-term follow-up study extension (N = 1272 [females, n = 971; males, n = 301]). Serum was collected at months 66 and 90 to assess antibody responses. For effectiveness analysis, genital swabs were collected (to assess HPV DNA by polymerase chain reaction [PCR]) and external genital examination was conducted (to detect external genital lesions) every 6 months starting when the participant reached 16 years of age. Cervical cytology tests were conducted annually when female participants reached 21 years of age; participants with cytological abnormalities were triaged to colposcopy based on a protocol-specified algorithm. External genital and cervical biopsies of abnormal lesions were performed, and histological diagnoses were adjudicated by a pathology panel. Specimens were tested by PCR to detect HPV DNA.

Results: Geometric mean titers for each 9vHPV vaccine HPV type peaked around month 7 and gradually decreased through month 90. Seropositivity rates remained >90% through month 90 for each of the 9vHPV vaccine types by HPV immunoglobulin Luminex Immunoassay. No cases of HPV6/11/16/18/31/33/45/52/58-related high-grade intraepithelial neoplasia or genital warts were observed in the per-protocol population (n = 1107) based on a maximum follow-up of 8.2 years (median 7.6 years) post-Dose 3. Incidence rates of HPV6/11/16/18/31/33/45/52/58-related 6-month persistent infection in females and males were 49.2 and 37.3 per 10,000 person-years, respectively, which were within ranges expected in vaccinated cohorts. There were no vaccine-related SAEs or deaths during the period covered by this interim analysis.

Conclusions: The 9vHPV vaccine provided sustained immunogenicity and durable effectiveness through approximately 7 and 8 years, respectively, following vaccination of girls and boys aged 9-15 years.
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http://dx.doi.org/10.1016/j.pvr.2020.100203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396911PMC
December 2020

Stable HEV IgG seroprevalence in Belgium between 2006 and 2014.

J Viral Hepat 2020 11 12;27(11):1253-1260. Epub 2020 Jul 12.

Department of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, Belgium.

Recent European studies suggest an emergence of hepatitis E virus (HEV) infection. We evaluated trends in birth cohort-specific HEV seroprevalence and regional differences in Belgium. HEV IgG seroprevalence was analysed on national serum banks (1579 and 2087 samples for 2006 and 2014, respectively. Hepatitis E virus antigen was tested on positive samples. Observed data were modelled using a generalized additive model with a complementary log-log link. No significant differences between birth cohorts or sexes were found. Modelling identified the individual's age and province as relevant factors. The probability of HEV seropositivity increases significantly with age. An estimated total of 434 819 (yearly rate of 54,352) (sero-)infections were found between 2006 and 2014. Overall, HEV IgG seroprevalences were 4.1% (64/1579, 95% CI 3.1-5.1) and 5.8% (121/2087, CI 4.8-6.9) in 2006 and 2014, respectively. Observed HEV antigen seroprevalence was 0.027% (1/3666) for the entire cohort. These results show stable HEV IgG seroprevalence in Belgium.
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http://dx.doi.org/10.1111/jvh.13347DOI Listing
November 2020

Engineering the Live-Attenuated Polio Vaccine to Prevent Reversion to Virulence.

Cell Host Microbe 2020 05 23;27(5):736-751.e8. Epub 2020 Apr 23.

Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.chom.2020.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566161PMC
May 2020

Comparison of a VLP-based and GST-L1-based multiplex immunoassay to detect vaccine-induced HPV-specific antibodies in first-void urine.

J Med Virol 2020 Apr 8. Epub 2020 Apr 8.

Centre for the Evaluation of Vaccination (CEV); Vaccine & Infectious Disease Institute (VAXINFECTIO); Faculty of Medicine and Health Sciences; University of Antwerp, Belgium.

Background: Vaccine-induced human papillomavirus (HPV) antibodies originating from cervicovaginal secretions were recently shown to be detectable in first-void (FV) urine. This presents a novel opportunity for non-invasive sampling to monitor HPV antibody status in women participating in large epidemiological studies and HPV vaccine trials. With a view towards method optimization, this study compared measurement of HPV antibodies in FV urine using a multiplex L1/L2 virus-like particles (VLP)-based ELISA (M4ELISA) with previously reported results using a glutathione S-transferase (GST)-L1-based immunoassay (GST-L1-MIA).

Methods: We tested 53 paired FV urine and serum samples from 19- to 26-year-old healthy women, unvaccinated (n = 17) or vaccinated with either the bi- or quadrivalent HPV-vaccine during adolescence (n = 36). HPV6/11/16/18 antibodies were measured using M4ELISA and compared with GST-L1-MIA results. Inter-assay and inter-specimen correlations were examined using the Spearman's rank test (r ).

Findings: As expected, lower HPV antibody concentrations were found in FV urine than in serum. Vaccinated women had significantly higher HPV6/11/16/18 antibody levels in both FV urine and serum compared with those unvaccinated (M4ELISA; FV urine p = 0.0003; serum p ≤ 0.0001). HPV antibody levels in FV urine and serum showed a significant positive correlation (M4ELISA anti-HPV6/11/16/18, r = 0.85/0.86/0.91/0.79, p ≤ 0.001). Despite assay differences, there was moderate to good correlation between M4ELISA and GST-L1-MIA (FV urine anti-HPV6/11/16/18, r = 0.86/0.83/0.89/0.53, p ≤ 0.0001; serum anti-HPV6/11/16/18, r = 0.93/0.89/0.94/0.75, p ≤ 0.0001).

Conclusion: FV urine HPV antibody detection is comparable with both assays, further supporting this non-invasive sampling method as a possible option for HPV vaccine assessment. Approaches to improve the sensitivity and larger studies are warranted to determine the feasibility of FV urine for vaccine-induced HPV antibody detection. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/jmv.25841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687076PMC
April 2020

Safety and immunogenicity of fully liquid and lyophilized formulations of an investigational trivalent group B streptococcus vaccine in healthy non-pregnant women: Results from a randomized comparative phase II trial.

Vaccine 2020 04 10;38(16):3227-3234. Epub 2020 Mar 10.

GSK, Rockville, MD, United States. Electronic address:

Background: We evaluated the safety and immunogenicity of liquid and lyophilized formulations of an investigational trivalent group B streptococcus (GBS) vaccine in non-pregnant women and assessed the formulations' equivalence in terms of serotype-specific immune response.

Methods: This phase II, randomized, comparative, observer-blind trial enrolled healthy non-pregnant women 18-40 years of age. Women received a single dose of fully liquid (n = 529) or lyophilized (n = 521) trivalent GBS vaccine on day 1. Safety assessments were performed up to day 181 (study termination). Serotype Ia/Ib/III-specific immunoglobulin G (IgG) antibodies were measured in sera from women on day 1 (pre-vaccination) and day 31. Equivalence between the two formulations was demonstrated if the two-sided 95% confidence interval (CI) for the ratio (liquid/lyophilized) of the geometric mean concentrations (GMCs) on day 31 was contained in a (0.5, 2.0) interval for each serotype.

Results: Solicited and unsolicited adverse events were reported at similar rates for both formulations. Serious adverse events were reported for six (1.1%) liquid GBS and nine (1.7%) lyophilized GBS vaccinated women, none of which were considered related to vaccination or fatal. On day 31, serotype-specific IgG concentrations were 8-16-fold higher than on day 1 in both groups. Equivalence of the liquid to the lyophilized formulation 30 days post-vaccination was demonstrated as the 95% CIs of the GMC ratios were within the pre-specified interval for the three serotypes: GMC ratios were 1.02 (95% CI: 0.79, 1.32) for serotype Ia, 0.93 (0.71, 1.21) for serotype Ib and 0.99 (0.76, 1.30) for serotype III.

Conclusions: Both formulations of the investigational trivalent GBS vaccine had favorable safety profiles and induced similar GBS serotype-specific antibody concentrations. This study demonstrated that the fully liquid formulation was equivalent to the lyophilized formulation in healthy non-pregnant women in terms of immunogenicity for all three serotypes.

Clinical Trials Registration: NCT02270944.
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http://dx.doi.org/10.1016/j.vaccine.2020.02.085DOI Listing
April 2020

Transcriptomic profiling of different responder types in adults after a Priorix® vaccination.

Vaccine 2020 04 9;38(16):3218-3226. Epub 2020 Mar 9.

AUDACIS, Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing, University of Antwerp, Antwerp, Belgium; Centre for the Evaluation of Vaccination (CEV), Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium.

Thanks to the recommendation of a combined Measles/Mumps/Rubella (MMR) vaccine, like Priorix®, these childhood diseases are less common now. This is beneficial to limit the spread of these diseases and work towards their elimination. However, the measles, mumps and rubella antibody titers show a large variability in short- and long-term immunity. The recent outbreaks worldwide of measles and mumps and previous studies, which mostly focused on only one of the three virus responses, illustrate that there is a clear need for better understanding the immune responses after vaccination. Our healthy cohort was already primed with the MMR antigens in their childhood. In this study, the adult volunteers received one Priorix® vaccine dose at day 0. First, we defined 4 different groups of responders, based on their antibody titers' evolution over 4 time points (Day 0, 21, 150 and 365). This showed a high variability within and between individuals. Second, we determined transcriptome profiles using 3'mRNA sequencing at day 0, 3 and 7. Using two analytical approaches, "one response group per time point" and "a time comparison per response group", we correlated the short-term gene expression profiles to the different response groups. In general, the list of differentially expressed genes is limited, however, most of them are clearly immune-related and upregulated at day 3 and 7, compared to the baseline day 0. Depending on the specific response group there are overlapping signatures for two of the three viruses. Antibody titers and transcriptomics data showed that an additional Priorix vaccination does not facilitate an equal immune response against the 3 viruses or among different vaccine recipients.
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http://dx.doi.org/10.1016/j.vaccine.2020.03.004DOI Listing
April 2020