Publications by authors named "Ilse De Coster"

13 Publications

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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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December 2020

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 (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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January 2021

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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May 2020

Poliopolis: pushing boundaries of scientific innovations for disease eradication.

Future Microbiol 2019 10 4;14:1321-1330. Epub 2019 Sep 4.

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

Although global polio eradication is within reach, sustained eradication of all polioviruses requires cessation of oral poliovirus vaccine use to mitigate against vaccine-derived poliovirus circulation and vaccine-associated paralytic poliomyelitis. The first step in this direction was the WHO-recommended global withdrawal of live attenuated type 2 Sabin poliovirus from routine immunisation in May 2016, with future use restricted to outbreak response, and handling controlled by strict containment provisions (GAPIII). This creates unique challenges for development and testing of novel type 2 poliovirus vaccines. We describe the creation of a novel purpose-built containment facility, Poliopolis, to study new monovalent OPV2 vaccine candidates in healthy adult volunteers, which may be a model for future endeavors in vaccine development for emergency use.
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October 2019


Lancet 2019 07 11;394(10193):115. Epub 2019 Jul 11.

Bill & Melinda Gates Foundation, Seattle, WA, USA.

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July 2019

The safety and immunogenicity of two novel live attenuated monovalent (serotype 2) oral poliovirus vaccines in healthy adults: a double-blind, single-centre phase 1 study.

Lancet 2019 07 4;394(10193):148-158. Epub 2019 Jun 4.

Center for Vaccine Innovation and Access, PATH, Seattle, WA, USA.

Background: Use of oral live-attenuated polio vaccines (OPV), and injected inactivated polio vaccines (IPV) has almost achieved global eradication of wild polio viruses. To address the goals of achieving and maintaining global eradication and minimising the risk of outbreaks of vaccine-derived polioviruses, we tested novel monovalent oral type-2 poliovirus (OPV2) vaccine candidates that are genetically more stable than existing OPVs, with a lower risk of reversion to neurovirulence. Our study represents the first in-human testing of these two novel OPV2 candidates. We aimed to evaluate the safety and immunogenicity of these vaccines, the presence and extent of faecal shedding, and the neurovirulence of shed virus.

Methods: In this double-blind, single-centre phase 1 trial, we isolated participants in a purpose-built containment facility at the University of Antwerp Hospital (Antwerp, Belgium), to minimise the risk of environmental release of the novel OPV2 candidates. Participants, who were recruited by local advertising, were adults (aged 18-50 years) in good health who had previously been vaccinated with IPV, and who would not have any contact with immunosuppressed or unvaccinated people for the duration of faecal shedding at the end of the study. The first participant randomly chose an envelope containing the name of a vaccine candidate, and this determined their allocation; the next 14 participants to be enrolled in the study were sequentially allocated to this group and received the same vaccine. The subsequent 15 participants enrolled after this group were allocated to receive the other vaccine. Participants and the study staff were masked to vaccine groups until the end of the study period. Participants each received a single dose of one vaccine candidate (candidate 1, S2/cre5/S15domV/rec1/hifi3; or candidate 2, S2/S15domV/CpG40), and they were monitored for adverse events, immune responses, and faecal shedding of the vaccine virus for 28 days. Shed virus isolates were tested for the genetic stability of attenuation. The primary outcomes were the incidence and type of serious and severe adverse events, the proportion of participants showing viral shedding in their stools, the time to cessation of viral shedding, the cell culture infective dose of shed virus in virus-positive stools, and a combined index of the prevalence, duration, and quantity of viral shedding in all participants. This study is registered with EudraCT, number 2017-000908-21 and, number NCT03430349.

Findings: Between May 22 and Aug 22, 2017, 48 volunteers were screened, of whom 15 (31%) volunteers were excluded for reasons relating to the inclusion or exclusion criteria, three (6%) volunteers were not treated because of restrictions to the number of participants in each group, and 30 (63%) volunteers were sequentially allocated to groups (15 participants per group). Both novel OPV2 candidates were immunogenic and increased the median blood titre of serum neutralising antibodies; all participants were seroprotected after vaccination. Both candidates had acceptable tolerability, and no serious adverse events occurred during the study. However, severe events were reported in six (40%) participants receiving candidate 1 (eight events) and nine (60%) participants receiving candidate 2 (12 events); most of these events were increased blood creatinine phosphokinase but were not accompanied by clinical signs or symptoms. Vaccine virus was detected in the stools of 15 (100%) participants receiving vaccine candidate 1 and 13 (87%) participants receiving vaccine candidate 2. Vaccine poliovirus shedding stopped at a median of 23 days (IQR 15-36) after candidate 1 administration and 12 days (1-23) after candidate 2 administration. Total shedding, described by the estimated median shedding index (50% cell culture infective dose/g), was observed to be greater with candidate 1 than candidate 2 across all participants (2·8 [95% CI 1·8-3·5] vs 1·0 [0·7-1·6]). Reversion to neurovirulence, assessed as paralysis of transgenic mice, was low in isolates from those vaccinated with both candidates, and sequencing of shed virus indicated that there was no loss of attenuation in domain V of the 5'-untranslated region, the primary site of reversion in Sabin OPV.

Interpretation: We found that the novel OPV2 candidates were safe and immunogenic in IPV-immunised adults, and our data support the further development of these vaccines to potentially be used for maintaining global eradication of neurovirulent type-2 polioviruses.

Funding: Bill & Melinda Gates Foundation.
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July 2019

Safety and Immunogenicity of Different Formulations of Norovirus Vaccine Candidate in Healthy Adults: A Randomized, Controlled, Double-Blind Clinical Trial.

J Infect Dis 2018 01;217(4):597-607

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

Background: We investigated safety and immunogenicity of 1-2 doses of different bivalent virus-like particle (VLP) norovirus vaccine candidate (NoV) formulations in healthy 18- to 64-year-olds.

Methods: On days 1 and 28, participants (n = 420) randomized to 14 equal groups received intramuscular control vaccine (hepatitis A) or 1 of 11 NoV formulations containing varying dosages of GI.1 and GII.4c genotype VLP antigens with aluminum hydroxide [Al(OH)3], and 0 μg, 15 μg, or 50 μg monophosphoryl lipid A (MPL). Immunogenicity was assessed on days 1, 28, 56, 208 and 393. Solicited local and systemic reactions were recorded for 7 days, unsolicited adverse events (AEs) until day 56, and serious AEs throughout the trial.

Results: All NoV formulations induced similar increases in pan-immunoglobulin, immunoglobulin A, and histo-blood group binding antigen-blocking antibodies by day 56, mostly after 1 dose, that persisted above baseline to day 393. Higher GI.1 content interfered with GII.4c responses, and responses did not benefit from MPL. Overall reactogenicity consisted of mainly mild injection site pain, headache, and fatigue. No vaccine-related serious AEs were reported.

Conclusions: All candidate NoV formulations were well tolerated. Overall, 15 μg GI.1/50 μg GII.4c elicited the best balance of immunogenicity with no clear benefit of MPL, and is the candidate formulation being taken forward in clinical development.

Clinical Trials Registration: NCT02038907.
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January 2018

GTL001, A Therapeutic Vaccine for Women Infected with Human Papillomavirus 16 or 18 and Normal Cervical Cytology: Results of a Phase I Clinical Trial.

Clin Cancer Res 2016 07 1;22(13):3238-48. Epub 2016 Jun 1.

Genticel, Paris, France.

Purpose: Women infected with human papillomavirus (HPV) with normal cytology to mild abnormalities currently have no treatment options other than watchful waiting or surgery if high-grade cervical lesions or cancer develop. A therapeutic vaccine would offer the possibility of preventing high-grade lesions in HPV-infected women. GTL001 is a therapeutic vaccine composed of recombinant HPV16 and HPV18 E7 proteins fused to catalytically inactive Bordetella pertussis CyaA. This study examined the tolerability and immunogenicity of GTL001 in women infected with HPV16 or HPV18 with normal cytology.

Experimental Design: This was a phase I trial (EudraCT No. 2010-018629-21). In an open-label part, subjects received two intradermal vaccinations 6 weeks apart of 100 or 600 μg GTL001 + topical 5% imiquimod cream at the injection site. In a double-blind part, subjects were randomized 2:1:1 to two vaccinations 6 weeks apart of 600 μg GTL001 + imiquimod, 600 μg GTL001 + placebo cream, or placebo + imiquimod.

Results: Forty-seven women were included. No dropouts, treatment-related serious adverse events, or dose-limiting toxicities occurred. Local reactions were transient and mostly mild or moderate. HPV16/18 viral load decreased the most in the 600 μg GTL001 + imiquimod group. In post hoc analyses, the 600 μg GTL001 + imiquimod group had the highest rates of initial and sustained HPV16/18 clearance. Imiquimod increased antigen-specific T-cell response rates but not rates of solicited reactions. All subjects seroconverted to CyaA.

Conclusions: For women infected with HPV16 or HPV18 with normal cervical cytology, GTL001 was immunogenic and had acceptable safety profile. Clin Cancer Res; 22(13); 3238-48. ©2016 AACR.
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July 2016

Long-Term Follow-up of HPV Infection Using Urine and Cervical Quantitative HPV DNA Testing.

Int J Mol Sci 2016 May 17;17(5). Epub 2016 May 17.

Centre for the Evaluation of Vaccination, Vaccine & Infectious Disease Institute, University of Antwerp, 2610 Wilrijk, Belgium.

The link between infection with high-risk human papillomavirus (hrHPV) and cervical cancer has been clearly demonstrated. Virological end-points showing the absence of persistent HPV infection are now accepted as a way of monitoring the impact of prophylactic vaccination programs and therapeutic vaccine trials. This study investigated the use of urine samples, which can be collected by self-sampling at home, instead of cervical samples for follow-up of an HPV intervention trial. Eighteen initially HPV DNA-positive women participating in an HPV therapeutic vaccine trial were monitored during a three-year follow-up period. A total of 172 urine samples and 85 cervical samples were collected. We obtained a paired urine sample for each of the 85 cervical samples by recovering urine samples from six monthly gynaecological examinations. We performed a small pilot study in which the participating women used a urine collection device at home and returned their urine sample to the laboratory by mail. All samples were analyzed using quantitative real-time HPV DNA PCR. A good association (κ value of 0.65) was found between the presence of HPV DNA in urine and a subsequent cervical sample. Comparisons of the number of HPV DNA copies in urine and paired cervical samples revealed a significant Spearman rho of 0.676. This correlation was superior in women with severe lesions. The HPV DNA results of the small pilot study based on self-collected urine samples at home are consistent with previous and subsequent urine and/or cervical results. We demonstrated that urine sampling may be a valid alternative to cervical samples for the follow-up of HPV intervention trials or programs. The potential clinical value of urine viral load monitoring should be further investigated.
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May 2016

A decade of norovirus disease risk among older adults in upper-middle and high income countries: a systematic review.

BMC Infect Dis 2015 Oct 14;15:425. Epub 2015 Oct 14.

P95 Pharmacovigilance and Epidemiology Services, Leuven, Belgium.

Background: Noroviruses (NoVs) are the most common cause of acute gastroenteritis (AGE) causing both sporadic and outbreak-associated illness. Norovirus (NoV) infections occur across all ages but certain sub-groups are considered at increased risk due to heightened transmission and/or symptom severity. Older adults are potentially at high risk of NoV-associated illness due to frequent outbreaks in long-term care facilities (LTCFs) and severe health outcomes following infection. Elucidation of NoV risk among older adults will support prevention, treatment and control efforts.

Methods: We conducted a systematic literature review to summarize the published risk estimates of NoV-associated illness, hospitalization and death among individuals aged 65 years and older. A structured search using defined NoV and gastroenteritis (GE) terms was performed in the PubMed and EMBASE databases of human studies published between January 1, 2003 and May 16, 2013.

Results: We identified 39 studies from high income (HI) and upper-middle income (UMI) countries. Thirty-six percent of publications provided risk estimates based on laboratory-confirmed or epidemiologically-linked population-based surveillance data using molecular diagnostic methods. Over the study period, estimated annual NoV rates and extrapolated number of cases among older adults in HI and UMI countries were: 29-120/10,000 or 1.2-4.8 million NoV-associated illnesses; 18-54/10,000 or 723,000-2.2 million NoV-associated outpatient visits; 1-19/10,000 or 40,00-763,000 NoV-associated inpatient visits; 0.04-0.32/10,000 or 2000-13,000 NoV-associated deaths. NoV was responsible for approximately 10-20 % of GE hospitalizations and 10-15 % of all-cause GE deaths among older adults. Older adults experienced a heightened risk of nosocomial infections. Those in LTCFs experience frequent NoV outbreaks and the range in attack rates was 3-45 %, case hospitalization rates 0.5-6 % and case fatality rates 0.3-1.6 %.

Conclusions: Older adults are at increased risk of severe NoV-associated health outcomes. NoV-associated hospitalization rates were higher, more severe, resulted in longer stays and incurred greater costs than for younger patients. NoV-associated mortality rates were approximately 200 % higher among individuals 65 years and older compared to <5 years. The burden of NoV among older adults is expected to rise along with societal aging and increased need for institutionalized care. NoV prevention in older adults, including potential vaccination, may significantly impact risk of severe illness.
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October 2015

Assessment of preparation time with fully-liquid versus non-fully liquid paediatric hexavalent vaccines. A time and motion study.

Vaccine 2015 Jul 17;33(32):3976-82. Epub 2015 Jun 17.

Faculty of Medicine and Health Sciences, Centre for the Evaluation of Vaccination, Vaccine & Infectious Disease Institute, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.

Background And Aims: Simplified vaccine preparation steps would save time and reduce potential immunisation errors. The aim of the study was to assess vaccine preparation time with fully-liquid hexavalent vaccine (DTaP-IPV-HB-PRP-T, Sanofi Pasteur MSD) versus non-fully liquid hexavalent vaccine that needs reconstitution (DTPa-HBV-IPV/Hib, GlaxoSmithKline Biologicals).

Methods: Ninety-six Health Care Professionals (HCPs) participated in a randomised, cross-over, open-label, time and motion study in Belgium (2014). HCPs prepared each vaccine in a cross-over manner with a wash-out period of 3-5min. An independent nurse assessed preparation time and immunisation errors by systematic review of the videos. HCPs satisfaction and preference were evaluated by a self-administered questionnaire.

Results: Average preparation time was 36s for the fully-liquid vaccine and 70.5s for the non-fully liquid vaccine. The time saved using the fully-liquid vaccine was 34.5s (p≤0.001). On 192 preparations, 57 immunisation errors occurred: 47 in the non-fully liquid vaccine group (including one missing reconstitution of Hib component), 10 in the fully-liquid vaccine group. 71.9% of HCPs were very or somewhat satisfied with the ease of handling of both vaccines; 66.7% and 67.7% were very or somewhat satisfied with speed of preparation in the fully-liquid vaccine and the non-fully liquid vaccine groups, respectively. Almost all HCPs (97.6%) stated they would prefer the use of the fully-liquid vaccine in their daily practice.

Conclusions: Preparation of a fully-liquid hexavalent vaccine can be completed in half the time necessary to prepare a non-fully liquid vaccine. The simplicity of the fully-liquid hexavalent vaccine preparation helps optimise reduction of immunisation errors.
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July 2015

Long-term antibody persistence in children after vaccination with the pediatric formulation of an aluminum-free virosomal hepatitis A vaccine.

Pediatr Infect Dis J 2015 Apr;34(4):e85-91

From the *Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium; †Department of Public Health, Ghent University, Ghent, Belgium; ‡GZA Campus Sint-Vincentius, Antwerp, Belgium; §Crucell Holland BV, Leiden, The Netherlands; and ¶Crucell Switzerland AG, Bern, Switzerland.

Background: The pediatric dose of the virosomal hepatitis A vaccine Epaxal, Epaxal Junior, is safe and immunogenic in children from 1 to 17 years of age. The present study investigated the long-term immunogenicity of Epaxal Junior. The standard doses of Epaxal and aluminum-adsorbed hepatitis A vaccine (Havrix Junior) were used as comparators.

Methods: A total of 271 children who had completed a 0/6-month immunization schedule (priming and booster dose) participated in this follow-up study. Anti-hepatitis A virus (HAV) antibody levels were measured using a microparticle enzyme immunoassay (HAVAB 2.0 Quantitative; Abbott Diagnostics, Wiesbaden, Germany) starting at 18 months following the second dose, and then yearly until 66 months (ie, 5.5 years) after the second dose.

Results: All subjects tested at Month 66 still had protective anti-HAV antibodies (≥10 mIU/mL). Antibody titers were generally lower in subjects 1-7 years old than in subjects 8-17 years old and higher in females 11-17 years old than in males 11-17 years old. In addition, an age-dependent decay was observed, that is, antibody decreased more rapidly in younger than in older children.

Conclusions: Vaccination of children with two doses of Epaxal Junior confers a real-time protection of at least 5.5 years. This protection is estimated to last approximately 25 years. Younger children showed lower antibody titers and a faster antibody decline than older children. Additional follow-up studies are needed beyond 5.5 years to further assess the long-term immunogenicity of Epaxal Junior.
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April 2015

Safety, immunogenicity and dose ranging of a new Vi-CRM₁₉₇ conjugate vaccine against typhoid fever: randomized clinical testing in healthy adults.

PLoS One 2011 30;6(9):e25398. Epub 2011 Sep 30.

Center for the Evaluation of Vaccination, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.

Background: Typhoid fever causes more than 21 million cases of disease and 200,000 deaths yearly worldwide, with more than 90% of the disease burden being reported from Asia. Epidemiological data show high disease incidence in young children and suggest that immunization programs should target children below two years of age: this is not possible with available vaccines. The Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi-CRM₁₉₇) for infant vaccination concomitantly with EPI vaccines, either starting at 6 weeks with DTP or at 9 months with measles vaccine. We report the results from a Phase 1 and a Phase 2 dose ranging trial with Vi-CRM₁₉₇ in European adults.

Methodology: Following randomized blinded comparison of single vaccination with either Vi-CRM₁₉₇ or licensed polysaccharide vaccines (both containing 25·0 µg of Vi antigen), a randomised observer blinded dose ranging trial was performed in the same center to compare three concentrations of Vi-CRM₁₉₇ (1·25 µg, 5·0 µg and 12·5 µg of Vi antigen) with the polysaccharide vaccine.

Principal Findings: All vaccines were well tolerated. Compared to the polysaccharide vaccine, Vi-CRM₁₉₇ induced a higher incidence of mild to moderate short lasting local pain. All Vi-CRM₁₉₇ formulations induced higher Vi antibody levels compared to licensed control, with clear dose response relationship.

Conclusions: Vi-CRM₁₉₇ did not elicit safety concerns, was highly immunogenic and is therefore suitable for further clinical testing in endemic populations of South Asia.

Trial Registration: NCT01123941 NCT01193907.
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January 2012