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1. Poliovirus immunity among adults in the Democratic Republic of the Congo: a cross-sectional serosurvey

Author

Alfonso, Vivian H, Voorman, Arie, Hoff, Nicole A, Weldon, William C, Gerber, Sue, Gadoth, Adva, Halbrook, Megan, Goldsmith, Amelia, Mukadi, Patrick, Doshi, Reena H, Ngoie-Mwamba, Guillaume, Fuller, Trevon L, Okitolonda-Wemakoy, Emile, Muyembe-Tamfum, Jean-Jacques, and Rimoin, Anne W

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Rare Diseases, Biodefense, Vaccine Related, Prevention, Clinical Research, Immunization, Emerging Infectious Diseases, Infectious Diseases, Infection, Good Health and Well Being, Adult, Aged, Child, Child, Preschool, Cross-Sectional Studies, Democratic Republic of the Congo, Disease Outbreaks, Female, Humans, Infant, Poliomyelitis, Poliovirus, Poliovirus Vaccine, Oral, Seroepidemiologic Studies, Polio, Vaccine-preventable diseases, Adult immunity, Demographic and Health Survey, Microbiology, Medical Microbiology, Clinical sciences, Medical microbiology, Public health
Abstract

BackgroundVaccination efforts to eradicate polio currently focus on children under 5 years of age, among whom most cases of poliomyelitis still occur. However, in the Democratic Republic of the Congo (DRC), an outbreak of wild poliovirus type 1 occurred in 2010-2011 in which 16% of cases occurred among adults; in a related outbreak in the neighboring Republic of Congo, 75% of cases occurred among the same adult age-group. Given that infected adults may transmit poliovirus, this study was designed to assess adult immunity against polioviruses.MethodsWe assessed poliovirus seroprevalence using dried blood spots from 5,526 adults aged 15-59 years from the 2013-2014 Demographic and Health Survey in the DRC.ResultsAmong adults in the DRC, 74%, 72%, and 57% were seropositive for neutralizing antibodies for poliovirus types 1, 2, and 3, respectively. For all three serotypes, seroprevalence tended to be higher among older age groups, those living in households with more children, and among women.ConclusionsProtection against poliovirus is generally low among adults in the DRC, particularly for type 3 poliovirus. The lack of acquired immunity in adults suggests a potentially limited poliovirus circulation over the lifetime of those surveyed (spanning 1954 through 2014) and transmission of vaccine-derived poliovirus in this age group while underscoring the risk of these outbreaks among adults in the DRC.

Published
2022

2. Assessing the mucosal intestinal and systemic humoral immunity of sequential schedules of inactivated poliovirus vaccine and bivalent oral poliovirus vaccine for essential immunization in Bangladesh: An open-label, randomized controlled trial

Author

Snider, Cynthia J., Zaman, Khalequ, Estivariz, Concepcion F., Aziz, Asma Binte, Yunus, Mohammad, Haque, Warda, Hendley, William S., Weldon, William C., Oberste, M. Steven, Pallansch, Mark A., Wassilak, Steven G.F., and Anand, Abhijeet

Published
2024
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4. 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

Author

Van Damme, Pierre, De Coster, Ilse, Bandyopadhyay, Ananda S, Revets, Hilde, Withanage, Kanchanamala, De Smedt, Philippe, Suykens, Leen, Oberste, M Steven, Weldon, William C, Costa-Clemens, Sue Ann, Clemens, Ralf, Modlin, John, Weiner, Amy J, Macadam, Andrew J, Andino, Raul, Kew, Olen M, Konopka-Anstadt, Jennifer L, Burns, Cara C, Konz, John, Wahid, Rahnuma, and Gast, Christopher

Subjects
Clinical Research, Biotechnology, Infectious Diseases, Clinical Trials and Supportive Activities, Rare Diseases, Prevention, Immunization, Vaccine Related, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, 3.4 Vaccines, Prevention of disease and conditions, and promotion of well-being, Infection, Good Health and Well Being, Adult, Antibodies, Viral, Double-Blind Method, Feces, Female, Humans, Immunogenicity, Vaccine, Male, Middle Aged, Poliomyelitis, Poliovirus, Poliovirus Vaccine, Oral, RNA, Viral, Single-Blind Method, Vaccines, Attenuated, Virulence, Virus Shedding, Young Adult, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundUse 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.MethodsIn 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 ClinicalTrials.gov, number NCT03430349.FindingsBetween 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.InterpretationWe 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.FundingBill & Melinda Gates Foundation.

Published
2019

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

Author

Bashorun, Adedapo O, Badjie Hydara, Mariama, Adigweme, Ikechukwu, Umesi, Ama, Danso, Baba, Johnson, Njilan, Sambou, Ngally Aboubacarr, Fofana, Sidat, Kanu, Francis J, Jeyaseelan, Visalakshi, Verma, Harish, Weldon, William C, Oberste, M Steven, Sutter, Roland W, Jeffries, David, Wathuo, Miriam, Mach, Ondrej, and Clarke, Ed

Published
2022
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8. Polio immunity and the impact of mass immunization campaigns in the Democratic Republic of the Congo

Author

Voorman, Arend, Hoff, Nicole A, Doshi, Reena H, Alfonso, Vivian, Mukadi, Patrick, Muyembe-Tamfum, Jean-Jacques, Wemakoy, Emile Okitolonda, Bwaka, Ado, Weldon, William, Gerber, Sue, and Rimoin, Anne W

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Rare Diseases, Emerging Infectious Diseases, Biodefense, Prevention, Vaccine Related, Clinical Research, Infectious Diseases, Immunization, Prevention of disease and conditions, and promotion of well-being, 3.4 Vaccines, Infection, Good Health and Well Being, Child, Preschool, Democratic Republic of the Congo, Disease Outbreaks, Female, Humans, Infant, Male, Mass Vaccination, Poliomyelitis, Poliovirus, Poliovirus Vaccine, Oral, Seroepidemiologic Studies, Vaccination, Seroprevalence, Mass vaccination, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundIn order to prevent outbreaks from wild and vaccine-derived poliovirus, maintenance of population immunity in non-endemic countries is critical.MethodsWe estimated population seroprevalence using dried blood spots collected from 4893 children 6-59months olds in the 2013-2014 Demographic and Health Survey in the Democratic Republic of the Congo (DRC).ResultsPopulation immunity was 81%, 90%, and 70% for poliovirus types 1, 2, and 3, respectively. Among 6-59-month-old children, 78% reported at least one dose of polio in routine immunization, while only 15% had three doses documented on vaccination cards. All children in the study had been eligible for at least two trivalent oral polio vaccine campaigns at the time of enrollment; additional immunization campaigns seroconverted 5.0%, 14%, and 5.5% of non-immune children per-campaign for types 1, 2, and 3, respectively, averaged over relevant campaigns for each serotype.ConclusionsOverall polio immunity was high at the time of the study, though pockets of low immunity cannot be ruled out. The DRC still relies on supplementary immunization campaigns, and this report stresses the importance of the quality and coverage of those campaigns over their quantity, as well as the importance of routine immunization.

Published
2017

9. 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

Author

De Coster, Ilse, Leroux-Roels, Isabel, Bandyopadhyay, Ananda S, Gast, Christopher, Withanage, Kanchanamala, Steenackers, Katie, De Smedt, Philippe, Aerssens, Annelies, Leroux-Roels, Geert, Oberste, M Steven, Konopka-Anstadt, Jennifer L, Weldon, William C, Fix, Alan, Konz, John, Wahid, Rahnuma, Modlin, John, Clemens, Ralf, Costa Clemens, Sue Ann, Bachtiar, Novilia S, and Van Damme, Pierre

Published
2021
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10. Safety and immunogenicity of two novel type 2 oral poliovirus vaccine candidates compared with a monovalent type 2 oral poliovirus vaccine in children and infants: two clinical trials

Author

Sáez-Llorens, Xavier, Bandyopadhyay, Ananda S, Gast, Christopher, Leon, Tirza De, DeAntonio, Rodrigo, Jimeno, Jose, Caballero, Maria Isabel, Aguirre, Gabriela, Oberste, M Steven, Weldon, William C, Konopka-Anstadt, Jennifer L, Modlin, John, Bachtiar, Novilia S, Fix, Alan, Konz, John, Clemens, Ralf, Costa Clemens, Sue Ann, and Rüttimann, Ricardo

Published
2021
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14. Intestinal Immunity to Poliovirus Following Sequential Trivalent Inactivated Polio Vaccine/Bivalent Oral Polio Vaccine and Trivalent Inactivated Polio Vaccine–only Immunization Schedules : Analysis of an Open-label, Randomized, Controlled Trial in Chilean Infants

Author

Brickley, Elizabeth B., Wieland-Alter, Wendy, Connor, Ruth I., Ackerman, Margaret E., Boesch, Austin W., Arita, Minetaro, Weldon, William C., O’Ryan, Miguel G., Bandyopadhyay, Ananda S., and Wright, Peter F.

Published
2018

17. Trends in Poliovirus Seroprevalence in Kano State, Northern Nigeria

Author

Verma, Harish, Iliyasu, Zubairu, Craig, Kehinde T., Molodecky, Natalie A., Urua, Utibeabasi, Jibir, Binta Wudil, Gwarzo, Garba Dayyabu, Gajida, Auwalu U., McDonald, Sharla, Weldon, William C., Oberste, M. Steven, Braka, Fiona, Mkanda, Pascal, and Sutter, Roland W.

Published
2018

18. Assessment of genetic changes and neurovirulence of shed Sabin and novel type 2 oral polio vaccine viruses

Author

Wahid, Rahnuma, Mercer, Laina, Macadam, Andrew, Carlyle, Sarah, Stephens, Laura, Martin, Javier, Chumakov, Konstantin, Laassri, Majid, Petrovskaya, Svetlana, Smits, Saskia L., Stittelaar, Koert J., Gast, Chris, Weldon, William C., Konopka-Anstadt, Jennifer L., Steven Oberste, M., Van Damme, Pierre, De Coster, Ilse, Rüttimann, Ricardo, Bandyopadhyay, Ananda, and Konz, John

Published
2021
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27. Neutralizing Antibody against Enterovirus D68 in Children and Adults before 2014 Outbreak, Kansas City, Missouri, USA

Author

Harrison, Christopher J., Weldon, William C., Pahud, Barbara A., Jackson, Mary Anne, Oberste, M. Steven, and Selvarangan, Rangaraj

Subjects
Antibodies -- Usage, Child health -- Analysis, Epidemiology -- Analysis, Enterovirus infections -- Care and treatment -- Patient outcomes, Respiratory symptoms, Health
Abstract

The first enterovirus D68 (EV-D68) isolate (Fermon) was identified in 1962 (1,2). Before a 2014 EV-D68 outbreak, US reports of EV-D68 were relatively sparse ( The Study We assessed the [...]

Published
2019
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33. Specific and sensitive detection tools for Xanthomonas arboricola pv. corylina, the causal agent of bacterial blight of hazelnut, developed with comparative genomics

Author

Kałużna, Monika, Kałużna, Monika, Prokić, Andjelka, Obradović, Aleksa, Weldon, William A., Stockwell, Virginia O., Pothier, Joël F., Kałużna, Monika, Kałużna, Monika, Prokić, Andjelka, Obradović, Aleksa, Weldon, William A., Stockwell, Virginia O., and Pothier, Joël F.

Abstract

Xanthomonas arboricola pv. corylina (Xac; formerly Xanthomonas campestris pv. corylina) is the causal agent of the bacterial blight of hazelnuts, a devastating disease of trees in plant nurseries and young orchards. Currently, there are no PCR assays to distinguish Xac from all other pathovars of X. arboricola. A comparative genomics approach with publicly available genomes of Xac was used to identify unique sequences, conserved across the genomes of the pathogen. We identified a 2,440 bp genomic region that was unique to Xac and designed identification and detection systems for conventional PCR, qPCR (SYBR® Green and TaqMan™), and loop-mediated isothermal amplification (LAMP). All PCR assays performed on genomic DNA isolated from eight X. arboricola pathovars and closely related bacterial species confirmed the specificity of designed primers. These new multi-platform molecular diagnostic tools may be used by plant clinics and researchers to detect and identify Xac in pure cultures and hazelnut tissues rapidly and accurately.

Published
2023

36. Humoral and intestinal immunity induced by new schedules of bivalent oral poliovirus vaccine and one or two doses of inactivated poliovirus vaccine in Latin American infants: an open-label randomised controlled trial

Author

Asturias, Edwin J, Bandyopadhyay, Ananda S, Self, Steve, Rivera, Luis, Saez-Llorens, Xavier, Lopez, Eduardo, Melgar, Mario, Gaensbauer, James T, Weldon, William C, Oberste, M Steven, Borate, Bhavesh R, Gast, Chris, Clemens, Ralf, Orenstein, Walter, O'Ryan G, Miguel, Jimeno, José, Clemens, Sue Ann Costa, Ward, Joel, and Rüttimann, Ricardo

Published
2016
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45. EXPERIMENTAL ASSESSMENT OF THE EFFECTIVENESS OF UNMANNED AERIAL SYSTEMS IN SEARCH AND RESCUE.pdf

Author

Weldon, William Theodore

Subjects
Disaster and emergency management
Abstract

A search and rescue (SAR) operation requires a rapid, accurate, and effective response to provide the missing person the best chance of being rescued. Personnel from the local area are likely to be closest to the location of the missing person, be familiar with the area, but they may not be adequately trained, experienced, or equipped with the best tools to effectively locate, identify, and retrieve the missing person. Thus, most SAR operations rely on a mix of trained personnel and volunteers. Among the trained personnel, there is a wide variance in proficiency, experience, and access to technology, leading to some emergency response agencies being better prepared than others. Volunteers, on the other hand, could be very helpful, but are largely untrained and inexperienced, reducing their inherent likelihood of success. The primary challenge to successful SAR operations is the lack of consistently trained, adequately equipped, and diversely experienced personnel. Despite the lack of desired resources, SAR operations must be completed rapidly and emergency responders often turn to volunteers. In response to this challenge, the use of unmanned aerial systems, UAS, in small volunteer teams was proposed. Available, off-the-shelf UAS technology can be used to simplify training with the help of affordable advanced technology, and thereby enable rapid, accurate, and effective SAR operations. The following research was executed in the form of three independent, but related, studies. The first study focused on the efficiency of a UAS-equipped SAR operation; the second study focused on the accuracy of a UAS and image analysis software-enabled SAR operation; and the third study tested the ability of novice volunteers to learn and apply the new technologies (UAS plus image analysis) efficiently and effectively. The goal of these studies was to determine whether affordable commercial, off-the-shelf technologies could be used to enhance the efficiency and effectivity of SAR operations. The experimental methodology used specifically designed simulations of SAR operational scenarios. Two operational tactics were tested: (a) Equip the SAR team with UAS and (b) equip the SAR team with UAS and image analysis software. The specific scenarios selected were similar in complexity, but different enough to minimize the transfer of learning from the first study to the second study. Finally, the reference times for manual SAR operations were compared against UAS and computerized image analysis software-assisted methods. The results of the proposed studies determined whether off-the-shelf UAS and image analysis technologies could be used to enable rapid, accurate, and effective SAR operations.

Published
2023
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47. Factors Contributing to Outbreaks of Wild Poliovirus Type 1 Infection Involving Persons Aged > 15 Years in the Democratic Republic of the Congo, 2010-2011, Informed by a Pre-Outbreak Poliovirus Immunity Assessment

Author

Alleman, Mary M., Wannemuehler, Kathleen A., Weldon, William C., Kabuayi, Jean Pierre, Ekofo, Felly, Edidi, Samuel, Mulumba, Audry, Mbule, Albeit, Ntumbannji, Renée N., Coulibaly, Tiekoura, Abiola, Nadine, Mpingulu, Minlangu, Sidibe, Kassim, and Oberste, M. Steven

Published
2014

49. Co-administration of Oral Cholera Vaccine With Oral Polio Vaccine Among Bangladeshi Young Children: A Randomized Controlled Open Label Trial to Assess Interference

Author

Islam, Md Taufiqul, primary, Date, Kashmira, additional, Khan, Ashraful Islam, additional, Bhuiyan, Taufiqur Rahman, additional, Khan, Zahid Hasan, additional, Ahmed, Shamim, additional, Hossain, Motaher, additional, Khaton, Fatema, additional, Zaman, K, additional, McMillan, Nigel A J, additional, Anand, Abhijeet, additional, An, Qian, additional, Zhang, Chenhua, additional, Weldon, William C, additional, Yu, Alexander, additional, Luby, Stephen, additional, and Qadri, Firdausi, additional

Published
2022
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