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Response to and monitoring of viral outbreaks can be efficiently focused when rapid, quantitative, kinetic information provides the location and the number of infected individuals. Environmental surveillance traditionally provides information on location of populations with contagious, infected individuals since infectious poliovirus is excreted whether infections are asymptomatic or symptomatic. Here, we describe development of rapid (1 week turnaround time, TAT), quantitative RT-PCR of poliovirus RNA extracted directly from concentrated environmental surveillance samples to infer the number of infected individuals excreting poliovirus. The quantitation method was validated using data from vaccination with bivalent oral polio vaccine (bOPV). The method was then applied to infer the weekly number of excreters in a large, sustained, asymptomatic outbreak of wild type 1 poliovirus in Israel (2013) in a population where >90% of the individuals received three doses of inactivated polio vaccine (IPV). Evidence-based intervention strategies were based on the short TAT for direct quantitative detection. Furthermore, a TAT shorter than the duration of poliovirus excretion allowed resampling of infected individuals. Finally, the method documented absence of infections after successful intervention of the asymptomatic outbreak. The methodologies described here can be applied to outbreaks of other excreted viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), where there are (1) significant numbers of asymptomatic infections; (2) long incubation times during which infectious virus is excreted; and (3) limited resources, facilities, and manpower that restrict the number of individuals who can be tested and re-tested.
Yuri Perepliotchikov; Tomer Ziv-Baran; Musa Hindiyeh; Yossi Manor; Danit Sofer; Jacob Moran-Gilad; Laura Stephens; Ella Mendelson; Merav Weil; Ravit Bassal; Emilia Anis; Shepherd Singer; Ehud Kaliner; Gillian Cooper; Manasi Majumdar; Michal Markovich; Daniela Ram; Itamar Grotto; Ronni Gamzu; Javier Martin; Lester Shulman. Inferring Numbers of Wild Poliovirus Excretors Using Quantitative Environmental Surveillance. Vaccines 2021, 9, 870 .
AMA StyleYuri Perepliotchikov, Tomer Ziv-Baran, Musa Hindiyeh, Yossi Manor, Danit Sofer, Jacob Moran-Gilad, Laura Stephens, Ella Mendelson, Merav Weil, Ravit Bassal, Emilia Anis, Shepherd Singer, Ehud Kaliner, Gillian Cooper, Manasi Majumdar, Michal Markovich, Daniela Ram, Itamar Grotto, Ronni Gamzu, Javier Martin, Lester Shulman. Inferring Numbers of Wild Poliovirus Excretors Using Quantitative Environmental Surveillance. Vaccines. 2021; 9 (8):870.
Chicago/Turabian StyleYuri Perepliotchikov; Tomer Ziv-Baran; Musa Hindiyeh; Yossi Manor; Danit Sofer; Jacob Moran-Gilad; Laura Stephens; Ella Mendelson; Merav Weil; Ravit Bassal; Emilia Anis; Shepherd Singer; Ehud Kaliner; Gillian Cooper; Manasi Majumdar; Michal Markovich; Daniela Ram; Itamar Grotto; Ronni Gamzu; Javier Martin; Lester Shulman. 2021. "Inferring Numbers of Wild Poliovirus Excretors Using Quantitative Environmental Surveillance." Vaccines 9, no. 8: 870.
Sabin-strain oral polio vaccines (OPV) can, in rare instances, cause disease in recipients and susceptible contacts or evolve to become circulating vaccine-derived strains with the potential to cause outbreaks. Two novel type 2 OPV (nOPV2) candidates were designed to stabilize the genome against the rapid reversion that is observed following vaccination with Sabin OPV type 2 (mOPV2). Next-generation sequencing and a modified transgenic mouse neurovirulence test were applied to shed nOPV2 viruses from phase 1 and 2 studies and shed mOPV2 from a phase 4 study. The shed mOPV2 rapidly reverted in the primary attenuation site (domain V) and increased in virulence. In contrast, the shed nOPV2 viruses showed no evidence of reversion in domain V and limited or no increase in neurovirulence in mice. Based on these results and prior published data on safety, immunogenicity, and shedding, the nOPV2 viruses are promising alternatives to mOPV2 for outbreak responses.
Rahnuma Wahid; Laina Mercer; Andrew Macadam; Sarah Carlyle; Laura Stephens; Javier Martin; Konstantin Chumakov; Majid Laassri; Svetlana Petrovskaya; Saskia L. Smits; Koert J. Stittelaar; Chris Gast; William C. Weldon; Jennifer L. Konopka-Anstadt; M. Steven Oberste; Pierre Van Damme; Ilse De Coster; Ricardo Rüttimann; Ananda Bandyopadhyay; John Konz. Assessment of genetic changes and neurovirulence of shed Sabin and novel type 2 oral polio vaccine viruses. npj Vaccines 2021, 6, 1 -11.
AMA StyleRahnuma Wahid, Laina Mercer, Andrew Macadam, Sarah Carlyle, Laura Stephens, Javier Martin, Konstantin Chumakov, Majid Laassri, Svetlana Petrovskaya, Saskia L. Smits, Koert J. Stittelaar, Chris Gast, William C. Weldon, Jennifer L. Konopka-Anstadt, M. Steven Oberste, Pierre Van Damme, Ilse De Coster, Ricardo Rüttimann, Ananda Bandyopadhyay, John Konz. Assessment of genetic changes and neurovirulence of shed Sabin and novel type 2 oral polio vaccine viruses. npj Vaccines. 2021; 6 (1):1-11.
Chicago/Turabian StyleRahnuma Wahid; Laina Mercer; Andrew Macadam; Sarah Carlyle; Laura Stephens; Javier Martin; Konstantin Chumakov; Majid Laassri; Svetlana Petrovskaya; Saskia L. Smits; Koert J. Stittelaar; Chris Gast; William C. Weldon; Jennifer L. Konopka-Anstadt; M. Steven Oberste; Pierre Van Damme; Ilse De Coster; Ricardo Rüttimann; Ananda Bandyopadhyay; John Konz. 2021. "Assessment of genetic changes and neurovirulence of shed Sabin and novel type 2 oral polio vaccine viruses." npj Vaccines 6, no. 1: 1-11.
The recent appearance and growth of new SARS-CoV-2 variants represent a major challenge for the control of the COVID-19 pandemic. These variants of concern contain mutations affecting antigenicity, which raises concerns on their possible impact on human immune response to the virus and vaccine efficacy against them.
Thomas Wilton; Erika Bujaki; Dimitra Klapsa; Manasi Majumdar; Maria Zambon; Martin Fritzsche; Ryan Mate; Javier Martin. Rapid Increase of SARS-CoV-2 Variant B.1.1.7 Detected in Sewage Samples from England between October 2020 and January 2021. mSystems 2021, 6, e0035321 .
AMA StyleThomas Wilton, Erika Bujaki, Dimitra Klapsa, Manasi Majumdar, Maria Zambon, Martin Fritzsche, Ryan Mate, Javier Martin. Rapid Increase of SARS-CoV-2 Variant B.1.1.7 Detected in Sewage Samples from England between October 2020 and January 2021. mSystems. 2021; 6 (3):e0035321.
Chicago/Turabian StyleThomas Wilton; Erika Bujaki; Dimitra Klapsa; Manasi Majumdar; Maria Zambon; Martin Fritzsche; Ryan Mate; Javier Martin. 2021. "Rapid Increase of SARS-CoV-2 Variant B.1.1.7 Detected in Sewage Samples from England between October 2020 and January 2021." mSystems 6, no. 3: e0035321.
Enterovirus A-71 (EV71) is a global, highly contagkkious pathogen responsible for severe cases of hand-food-mouth-disease (HFMD). The use of vaccines eliciting cross neutralizing antibodies (NTAbs) against the different circulating EV71 sub-genotypes is important for preventing HFMD outbreaks. Here, we tested the cross-neutralizing activities induced by EV71 genotype/sub-genotype A, B0-B4, C1, C2, C4, and C5 viruses using rats. Differences were noted in the cross-neutralization of the 10 sub-genotypes tested but there were generally good levels of cross-neutralization except against genotype A virus, against which neutralization antibody titres (NTAb) where the lowest with NTAbs being the highest against sub-genotype B4. Moreover, NTAb responses induced by C4, B4, C1, and C2 viruses were homogenous, with values of maximum/minimum NTAb ratios (MAX/MIN) against all B and C viruses ranging between 4.0 and 6.0, whereas MAX/MIN values against B3 and A viruses were highly variable, 48.0 and 256.0, respectively. We then dissected the cross-neutralizing ability of sera from infants and children and rats immunized with C4 EV71 vaccines. Cross-neutralizing titers against the 10 sub-genotypes were good in both vaccinated infants and children and rats with the MAX/MIN ranging from 1.8–3.4 and 5.1–7.1, respectively, which were similar to those found in naturally infected patients (2.8). Therefore, we conclude that C4 EV71 vaccines can provide global protection to infants and children against HFMD caused by different sub-genotypes.
Pei Liu; Yadi Yuan; Bopei Cui; Yaqian Huo; Lianlian Bian; Lei Chen; Siyuan Liu; Chenfei Wang; Yingzhi Xu; Alison Tedcastle; Fan Gao; Qunying Mao; Javier Martin; Zhenglun Liang. Cross-Antigenicity between EV71 Sub-Genotypes: Implications for Vaccine Efficacy. Viruses 2021, 13, 720 .
AMA StylePei Liu, Yadi Yuan, Bopei Cui, Yaqian Huo, Lianlian Bian, Lei Chen, Siyuan Liu, Chenfei Wang, Yingzhi Xu, Alison Tedcastle, Fan Gao, Qunying Mao, Javier Martin, Zhenglun Liang. Cross-Antigenicity between EV71 Sub-Genotypes: Implications for Vaccine Efficacy. Viruses. 2021; 13 (5):720.
Chicago/Turabian StylePei Liu; Yadi Yuan; Bopei Cui; Yaqian Huo; Lianlian Bian; Lei Chen; Siyuan Liu; Chenfei Wang; Yingzhi Xu; Alison Tedcastle; Fan Gao; Qunying Mao; Javier Martin; Zhenglun Liang. 2021. "Cross-Antigenicity between EV71 Sub-Genotypes: Implications for Vaccine Efficacy." Viruses 13, no. 5: 720.
There are increasing concerns of infections by enteroviruses (EVs) causing severe disease in humans. EV diagnostic laboratory methods show differences in sensitivity and specificity as well as the level of genetic information provided. We examined a detection method for EVs based on next generation sequencing (NGS) analysis of amplicons covering the entire capsid coding region directly synthesized from clinical samples. One hundred and twelve clinical samples from England; previously shown to be positive for EVs, were analyzed. There was high concordance between the results obtained by the new NGS approach and those from the conventional Sanger method used originally with agreement in the serotypes identified in the 83 samples that were typed by both methods. The sensitivity and specificity of the NGS method compared to those of the conventional Sanger sequencing typing assay were 94.74% (95% confidence interval, 73.97% to 99.87%) and 97.85% (92.45% to 99.74%) for Enterovirus A, 93.75% (82.80% to 98.69%) and 89.06% (78.75% to 95.49%) for Enterovirus B, 100% (59.04% to 100%) and 98.10% (93.29% to 99.77%) for Enterovirus C, and 100% (75.29% to 100%) and 100% (96.34% to 100%) for Enterovirus D. The NGS method identified five EVs in previously untyped samples as well as additional viruses in some samples, indicating co-infection. This method can be easily expanded to generate whole-genome EV sequences as we show here for EV-D68. Information from capsid and whole-genome sequences is critical to help identifying the genetic basis for changes in viral properties and establishing accurate spatial-temporal associations between EV strains of public health relevance.
Manasi Majumdar; Cristina Celma; Elaine Pegg; Krunal Polra; Jake Dunning; Javier Martin. Detection and Typing of Human Enteroviruses from Clinical Samples by Entire-Capsid Next Generation Sequencing. Viruses 2021, 13, 641 .
AMA StyleManasi Majumdar, Cristina Celma, Elaine Pegg, Krunal Polra, Jake Dunning, Javier Martin. Detection and Typing of Human Enteroviruses from Clinical Samples by Entire-Capsid Next Generation Sequencing. Viruses. 2021; 13 (4):641.
Chicago/Turabian StyleManasi Majumdar; Cristina Celma; Elaine Pegg; Krunal Polra; Jake Dunning; Javier Martin. 2021. "Detection and Typing of Human Enteroviruses from Clinical Samples by Entire-Capsid Next Generation Sequencing." Viruses 13, no. 4: 641.
Human enteroviruses (EVs) are highly prevalent in sewage and have been associated with human diseases with complications leading to severe neurological syndromes. We have used a recently developed molecular method to investigate the presence of EVs in eight samples collected in 2017–2018 from water streams contaminated by drainage channels in three different locations in Nigeria. A total of 93 human EV strains belonging to 45 different serotypes were identified, far exceeding the number of strains and serotypes found in similar samples in previous studies. Next generation sequencing analysis retrieved whole-capsid genomic nucleotide sequences of EV strains belonging to all four A, B, C, and D species. Our results further demonstrate the value of environmental surveillance for the detection of EV transmission of both serotypes commonly associated with clinical syndromes, such as EV-A71, and those that appear to circulate silently but could eventually cause outbreaks and disease. Several uncommon serotypes, rarely reported elsewhere, were detected such as EV-A119, EV-B87, EV-C116, and EV-D111. Ten EV serotypes were detected in Nigeria for the first time and two of them, CV-A12 and EV-B86, firstly described in Africa. This method can be expanded to generate whole-genome EV sequences as we show here for one EV-D111 strain. Our data revealed phylogenetic relationships of Nigerian sewage strains with EV strains reported elsewhere, mostly from African origin, and provided new insights into the whole-genome structure of emerging serotype EV-D111 and recombination events among EV-D serotypes.
Manasi Majumdar; Dimitra Klapsa; Thomas Wilton; Erika Bujaki; Maria Fernandez-Garcia; Temitope Faleye; Adefunke Oyero; Moses Adewumi; Kader Ndiaye; Johnson Adeniji; Javier Martin. High Diversity of Human Non-Polio Enterovirus Serotypes Identified in Contaminated Water in Nigeria. Viruses 2021, 13, 249 .
AMA StyleManasi Majumdar, Dimitra Klapsa, Thomas Wilton, Erika Bujaki, Maria Fernandez-Garcia, Temitope Faleye, Adefunke Oyero, Moses Adewumi, Kader Ndiaye, Johnson Adeniji, Javier Martin. High Diversity of Human Non-Polio Enterovirus Serotypes Identified in Contaminated Water in Nigeria. Viruses. 2021; 13 (2):249.
Chicago/Turabian StyleManasi Majumdar; Dimitra Klapsa; Thomas Wilton; Erika Bujaki; Maria Fernandez-Garcia; Temitope Faleye; Adefunke Oyero; Moses Adewumi; Kader Ndiaye; Johnson Adeniji; Javier Martin. 2021. "High Diversity of Human Non-Polio Enterovirus Serotypes Identified in Contaminated Water in Nigeria." Viruses 13, no. 2: 249.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), responsible for the ongoing coronavirus disease (COVID-19) pandemic, is frequently shed in faeces during infection, and viral RNA has recently been detected in sewage in some countries. We have investigated the presence of SARS-CoV-2 RNA in wastewater samples from South-East England between 14th January and 12th May 2020. A novel nested RT-PCR approach targeting five different regions of the viral genome improved the sensitivity of RT-qPCR assays and generated nucleotide sequences at sites with known sequence polymorphisms among SARS-CoV-2 isolates. We were able to detect co-circulating virus variants, some specifically prevalent in England, and to identify changes in viral RNA sequences with time consistent with the recently reported increasing global dominance of Spike protein G614 pandemic variant. Low levels of viral RNA were detected in a sample from 11th February, 3 days before the first case was reported in the sewage plant catchment area. SARS-CoV-2 RNA concentration increased in March and April, and a sharp reduction was observed in May, showing the effects of lockdown measures. We conclude that viral RNA sequences found in sewage closely resemble those from clinical samples and that environmental surveillance can be used to monitor SARS-CoV-2 transmission, tracing virus variants and detecting virus importations.
Javier Martin; Dimitra Klapsa; Thomas Wilton; Maria Zambon; Emma Bentley; Erika Bujaki; Martin Fritzsche; Ryan Mate; Manasi Majumdar. Tracking SARS-CoV-2 in Sewage: Evidence of Changes in Virus Variant Predominance during COVID-19 Pandemic. Viruses 2020, 12, 1144 .
AMA StyleJavier Martin, Dimitra Klapsa, Thomas Wilton, Maria Zambon, Emma Bentley, Erika Bujaki, Martin Fritzsche, Ryan Mate, Manasi Majumdar. Tracking SARS-CoV-2 in Sewage: Evidence of Changes in Virus Variant Predominance during COVID-19 Pandemic. Viruses. 2020; 12 (10):1144.
Chicago/Turabian StyleJavier Martin; Dimitra Klapsa; Thomas Wilton; Maria Zambon; Emma Bentley; Erika Bujaki; Martin Fritzsche; Ryan Mate; Manasi Majumdar. 2020. "Tracking SARS-CoV-2 in Sewage: Evidence of Changes in Virus Variant Predominance during COVID-19 Pandemic." Viruses 12, no. 10: 1144.
Global poliovirus surveillance involves virus isolation from stool and environmental samples, intratypic differential (ITD) by PCR and sequencing of the VP1 region to distinguish vaccine (Sabin), vaccine-derived and wild-type polioviruses and ensure an appropriate response. This cell-culture algorithm takes 2-3 weeks on average between sample receipt and sequencing. Direct detection of viral RNA using PCR allows faster detection but has traditionally faced challenges related to poor sensitivity and difficulties in sequencing common samples containing poliovirus and enterovirus mixtures. We present a nested PCR and nanopore sequencing protocol that allows rapid (99.9%. This novel method shows promise as a faster and safer alternative to cell-culture for the detection and real-time sequencing of polioviruses in stool and environmental samples.
Alexander G. Shaw; Manasi Majumdar; Catherine Troman; Áine O'toole; Blossom Benny; Dilip Abraham; Ira Praharaj; Gagandeep Kang; Salmaan Sharif; Muhammad Masroor Alam; Shahzad Shaukat; Mehar Angez; Adnan Khurshid; Nayab Mahmood; Yasir Arshad; Lubna Rehman; Ghulam Mujtaba; Ribqa Akthar; Muhammad Salman; Dimitra Klapsa; Yara Hajarha; Humayun Asghar; Ananda Bandyopadhyay; Andrew Rambaut; Javier Martin; Nicholas C Grassly. Rapid and sensitive direct detection and identification of poliovirus from stool and environmental surveillance samples using nanopore sequencing. 2020, 1 .
AMA StyleAlexander G. Shaw, Manasi Majumdar, Catherine Troman, Áine O'toole, Blossom Benny, Dilip Abraham, Ira Praharaj, Gagandeep Kang, Salmaan Sharif, Muhammad Masroor Alam, Shahzad Shaukat, Mehar Angez, Adnan Khurshid, Nayab Mahmood, Yasir Arshad, Lubna Rehman, Ghulam Mujtaba, Ribqa Akthar, Muhammad Salman, Dimitra Klapsa, Yara Hajarha, Humayun Asghar, Ananda Bandyopadhyay, Andrew Rambaut, Javier Martin, Nicholas C Grassly. Rapid and sensitive direct detection and identification of poliovirus from stool and environmental surveillance samples using nanopore sequencing. . 2020; ():1.
Chicago/Turabian StyleAlexander G. Shaw; Manasi Majumdar; Catherine Troman; Áine O'toole; Blossom Benny; Dilip Abraham; Ira Praharaj; Gagandeep Kang; Salmaan Sharif; Muhammad Masroor Alam; Shahzad Shaukat; Mehar Angez; Adnan Khurshid; Nayab Mahmood; Yasir Arshad; Lubna Rehman; Ghulam Mujtaba; Ribqa Akthar; Muhammad Salman; Dimitra Klapsa; Yara Hajarha; Humayun Asghar; Ananda Bandyopadhyay; Andrew Rambaut; Javier Martin; Nicholas C Grassly. 2020. "Rapid and sensitive direct detection and identification of poliovirus from stool and environmental surveillance samples using nanopore sequencing." , no. : 1.
Detection of enterovirus D68 (EV-D68) in wastewater samples from the UK between December 2014 and December 2018 showed a marked seasonal distribution with a high proportion of samples containing EV-D68 during periods when identification of this virus in clinical samples was most common. This includes a recent upsurge of EV-D68 detection in respiratory samples from the United Kingdom between August and December 2018 associated with cases of acute flaccid myelitis, following similar reports in the USA. Phylogenetic analysis of EV-D68 sewage strains demonstrated that strains belonging to distinct genetic clades followed the same temporal distribution as that observed for EV-D68 clinical strains in the UK and that they showed very close genetic relationship with EV-D68 strains circulating elsewhere in the world during the same periods. The results demonstrated a clear association between detecting EV-D68 in wastewater and finding it in clinical samples which was somehow unexpected given that EV-D68 is rarely detected in stool samples. We conclude that the use of environmental surveillance is a valuable tool to detect and monitor outbreaks due to EV-68 infection.
Manasi Majumdar; Thomas Wilton; Yara Hajarha; Dimitra Klapsa; Javier Martin. Detection of Enterovirus D68 in wastewater samples from the United Kingdom during outbreaks reported globally between 2015 and 2018. 2019, 738948 .
AMA StyleManasi Majumdar, Thomas Wilton, Yara Hajarha, Dimitra Klapsa, Javier Martin. Detection of Enterovirus D68 in wastewater samples from the United Kingdom during outbreaks reported globally between 2015 and 2018. . 2019; ():738948.
Chicago/Turabian StyleManasi Majumdar; Thomas Wilton; Yara Hajarha; Dimitra Klapsa; Javier Martin. 2019. "Detection of Enterovirus D68 in wastewater samples from the United Kingdom during outbreaks reported globally between 2015 and 2018." , no. : 738948.
Following the declaration of wild-type 2 poliovirus eradication in 2015, the type 2 component was removed from the live-attenuated oral polio vaccine (OPV). This change implies a need to improve global coverage through routine immunization with inactivated polio vaccine (IPV), to ensure type 2 immunity. Several manufacturers use Sabin OPV strains for IPV production (sIPV), rather than the usual wild-type strains used for conventional IPV (cIPV). However, in contrast to cIPV, potency assays for sIPV have not been standardized, no international references exist, and no antigen units have been defined for a sIPV human dose. Thus, sIPV products from different manufacturers cannot be compared, and the relationship between antigenicity and immunogenicity of sIPV is not well understood. A collaborative study was conducted in which laboratories used different methods to measure the antigen content of a set of sIPV and cIPV samples with an aim to identify a suitable reference for sIPV products. The study revealed differences in the reactivity of antibody reagents to cIPV and sIPV products. Homologous references are required to measure the antigen content of IPV products consistently. The first World Health Organization international standard for sIPV was established, with new, specific Sabin D-antigen units assigned.
Laura Crawt; Eleanor Atkinson; Alison Tedcastle; Elaine Pegg; Alexandre Dobly; Cai Wei; Shi Lei; Ping Ling; Changgui Li; Jiang Zheng; Yijing Wang; Huo Liqun; Sylvie Jorajuria; Gwenäelle Cozic; Dori Ugiyadi; Nia Kurniati; Susumu Ochiai; Miwako Miyazawa; Yuichi Someya; Takeshi Nishihama; Misaki Masafumi; Janny Westdijk; Saskia Crowe; Michelle De Graaf; Diana Kouiavskaia; Konstantin Chumakov; Philip Minor; Gillian Cooper; Peter Rigsby; Javier Martin; sIPV Study Group. Differences in Antigenic Structure of Inactivated Polio Vaccines Made From Sabin Live-Attenuated and Wild-Type Poliovirus Strains: Impact on Vaccine Potency Assays. Journal of Infectious Diseases 2019, 221, 544 -552.
AMA StyleLaura Crawt, Eleanor Atkinson, Alison Tedcastle, Elaine Pegg, Alexandre Dobly, Cai Wei, Shi Lei, Ping Ling, Changgui Li, Jiang Zheng, Yijing Wang, Huo Liqun, Sylvie Jorajuria, Gwenäelle Cozic, Dori Ugiyadi, Nia Kurniati, Susumu Ochiai, Miwako Miyazawa, Yuichi Someya, Takeshi Nishihama, Misaki Masafumi, Janny Westdijk, Saskia Crowe, Michelle De Graaf, Diana Kouiavskaia, Konstantin Chumakov, Philip Minor, Gillian Cooper, Peter Rigsby, Javier Martin, sIPV Study Group. Differences in Antigenic Structure of Inactivated Polio Vaccines Made From Sabin Live-Attenuated and Wild-Type Poliovirus Strains: Impact on Vaccine Potency Assays. Journal of Infectious Diseases. 2019; 221 (4):544-552.
Chicago/Turabian StyleLaura Crawt; Eleanor Atkinson; Alison Tedcastle; Elaine Pegg; Alexandre Dobly; Cai Wei; Shi Lei; Ping Ling; Changgui Li; Jiang Zheng; Yijing Wang; Huo Liqun; Sylvie Jorajuria; Gwenäelle Cozic; Dori Ugiyadi; Nia Kurniati; Susumu Ochiai; Miwako Miyazawa; Yuichi Someya; Takeshi Nishihama; Misaki Masafumi; Janny Westdijk; Saskia Crowe; Michelle De Graaf; Diana Kouiavskaia; Konstantin Chumakov; Philip Minor; Gillian Cooper; Peter Rigsby; Javier Martin; sIPV Study Group. 2019. "Differences in Antigenic Structure of Inactivated Polio Vaccines Made From Sabin Live-Attenuated and Wild-Type Poliovirus Strains: Impact on Vaccine Potency Assays." Journal of Infectious Diseases 221, no. 4: 544-552.
Maria Zambon; Javier Martin. Polio eradication: next steps and future challenges. Eurosurveillance 2018, 23, 1800625 .
AMA StyleMaria Zambon, Javier Martin. Polio eradication: next steps and future challenges. Eurosurveillance. 2018; 23 (47):1800625.
Chicago/Turabian StyleMaria Zambon; Javier Martin. 2018. "Polio eradication: next steps and future challenges." Eurosurveillance 23, no. 47: 1800625.
Background Enteroviruses are common human pathogens occasionally associated with severe disease, notoriously paralytic poliomyelitis caused by poliovirus. Other enterovirus serotypes such as enterovirus A71 and D68 have been linked to severe neurological syndromes. New enterovirus serotypes continue to emerge, some believed to be derived from nonhuman primates. However, little is known about the circulation patterns of many enterovirus serotypes and, in particular, the detailed enterovirus composition of sewage samples. Methods We used a next-generation sequencing approach analyzing reverse transcriptase polymerase chain reaction products synthesized directly from sewage concentrates. Results We determined whole-capsid genome sequences of multiple enterovirus strains from all 4 A to D species present in environmental samples from the United Kingdom, Senegal, and Pakistan. Conclusions Our results indicate complex enterovirus circulation patterns in human populations with differences in serotype composition between samples and evidence of sustained and widespread circulation of many enterovirus serotypes. Our analyses revealed known and divergent enterovirus strains, some of public health relevance and genetically linked to clinical isolates. Enteroviruses identified in sewage included vaccine-derived poliovirus and enterovirus D-68 stains, new enterovirus A71 and coxsackievirus A16 genogroups indigenous to Pakistan, and many strains from rarely reported serotypes. We show how this approach can be used for the early detection of emerging pathogens and to improve our understanding of enterovirus circulation in humans.
Manasi Majumdar; Salmaan Sharif; Dimitra Klapsa; Thomas Wilton; Muhammad Masroor Alam; Maria Dolores Fernandez Garcia; Lubna Rehman; Ghulam Mujtaba; Gina McAllister; Heli Harvala; Kate Templeton; Edward T Mee; Humayun Asghar; Kader Ndiaye; Philip D Minor; Javier Martin. Environmental Surveillance Reveals Complex Enterovirus Circulation Patterns in Human Populations. Open Forum Infectious Diseases 2018, 5, ofy250 .
AMA StyleManasi Majumdar, Salmaan Sharif, Dimitra Klapsa, Thomas Wilton, Muhammad Masroor Alam, Maria Dolores Fernandez Garcia, Lubna Rehman, Ghulam Mujtaba, Gina McAllister, Heli Harvala, Kate Templeton, Edward T Mee, Humayun Asghar, Kader Ndiaye, Philip D Minor, Javier Martin. Environmental Surveillance Reveals Complex Enterovirus Circulation Patterns in Human Populations. Open Forum Infectious Diseases. 2018; 5 (10):ofy250.
Chicago/Turabian StyleManasi Majumdar; Salmaan Sharif; Dimitra Klapsa; Thomas Wilton; Muhammad Masroor Alam; Maria Dolores Fernandez Garcia; Lubna Rehman; Ghulam Mujtaba; Gina McAllister; Heli Harvala; Kate Templeton; Edward T Mee; Humayun Asghar; Kader Ndiaye; Philip D Minor; Javier Martin. 2018. "Environmental Surveillance Reveals Complex Enterovirus Circulation Patterns in Human Populations." Open Forum Infectious Diseases 5, no. 10: ofy250.
Background: Human enteroviruses (EVs) have been linked with severe disease and syndromes as varied as acute respiratory illness, myocarditis, and flaccid paralysis. With global polio eradication on sight the focus of clinical investigations has expanded to the identification of other EV serotypes associated with severe neurological conditions such as EV-D68, responsible for large outbreaks in 2014 and 2016 that spread worldwide and were related with severe respiratory disease leading to acute myelitis in some cases. New EV serotypes with epidemic potential continue to emerge such as EV-C104, EV-C105, EV-C109, and EV-C117 identified in respiratory samples in recent years. Methods: We used a next generation sequencing (NGS) approach to detect multiple EV serotypes directly in a sewage concentrate from Glasgow (Scotland, United Kingdom) generating whole-capsid nucleotide sequences that were compared to sequences of cell culture isolates from this sewage sample and clinical EV isolates from GenBank. Results: Thirteen different serotypes belonging to all four A, B, C, and D EV species were identified in the sewage concentrate. EV strains closely related to EV-D68 epidemic isolates of B3 lineage reported in the United States and Europe in 2016 and to EV-C109 respiratory isolates found in Denmark and Netherlands in 2015 were identified. Conclusion: Environmental surveillance (ES) can effectively detect EV circulation in human populations. The use of NGS for ES can help overcoming the limitations of traditional cell culture and sequencing methods, which are selective and biased, and can contribute to the early detection and assessment of spread of emerging EV pathogens.
Manasi Majumdar; Javier Martin. Detection by Direct Next Generation Sequencing Analysis of Emerging Enterovirus D68 and C109 Strains in an Environmental Sample From Scotland. Frontiers in Microbiology 2018, 9, 1956 .
AMA StyleManasi Majumdar, Javier Martin. Detection by Direct Next Generation Sequencing Analysis of Emerging Enterovirus D68 and C109 Strains in an Environmental Sample From Scotland. Frontiers in Microbiology. 2018; 9 ():1956.
Chicago/Turabian StyleManasi Majumdar; Javier Martin. 2018. "Detection by Direct Next Generation Sequencing Analysis of Emerging Enterovirus D68 and C109 Strains in an Environmental Sample From Scotland." Frontiers in Microbiology 9, no. : 1956.
Environmental surveillance (EnvS)2 is an important tool for monitoring the presence of poliovirus in endemic and poliovirus free regions. Unlike acute flaccid paralysis (AFP)3 surveillance, EnvS can monitor large populations using small numbers of samples and detect the introduction of poliovirus even before the appearance of AFP cases. Early detection and timely response can prevent the onset of poliovirus associated AFP, as was demonstrated by silent poliovirus transmission in Israel in 2013. Although EnvS is currently recommended as supplementary to AFP surveillance, it is limited to laboratories with equipment for poliovirus concentration and to regions where samples can be easily transported under temperature controlled conditions to such facilities. However the highest risk of poliovirus re-emergence is in developing countries where such conditions do not exist. We developed and evaluated an affinity purification method using antibody or poliovirus receptor (CD155) presenting bacteriophage covered magnetic beads for poliovirus concentration. This method requires only simple, inexpensive and portable equipment. Though tested only on Sabin 1 spiked sewage samples it provided better recovery than our current polyethylene glycol (PEG)4/NaCl- based concentration method. On site use of this method might facilitate EnvS in currently inaccessible remote regions by significantly reducing the volume of sample that needs to be transported back to the laboratory under temperature-controlled conditions5.
Yuri Perepliotchikov; Itai Benhar; Yossi Manor; Thomas Wilton; Manasi Majumdar; Javier Martin; Ella Mendelson; Lester M. Shulman. A novel magnetic beads-based method for polioviral concentration from environmental samples. Journal of Virological Methods 2018, 260, 62 -69.
AMA StyleYuri Perepliotchikov, Itai Benhar, Yossi Manor, Thomas Wilton, Manasi Majumdar, Javier Martin, Ella Mendelson, Lester M. Shulman. A novel magnetic beads-based method for polioviral concentration from environmental samples. Journal of Virological Methods. 2018; 260 ():62-69.
Chicago/Turabian StyleYuri Perepliotchikov; Itai Benhar; Yossi Manor; Thomas Wilton; Manasi Majumdar; Javier Martin; Ella Mendelson; Lester M. Shulman. 2018. "A novel magnetic beads-based method for polioviral concentration from environmental samples." Journal of Virological Methods 260, no. : 62-69.
Enterovirus A71 (EV71) is the major causative agent of severe and fatal hand, foot and mouth disease. There is plenty of evidence that EV71 has circulated widely in the Western Pacific Region for the last twenty years. Vaccines against EV71 are already available or under development. A collaborative study to establish the 1st WHO International Standard for anti-EV71 serum (Human) was conducted to ensure that methods used to measure the serum neutralizing activity or antibody levels against EV71 are accurate, sensitive and reproducible. Two candidate samples as well as a third candidate reference containing low anti-EV71 antibody titre were produced from plasma samples donated by healthy individuals. All three serum samples exhibited good levels of neutralizing antibodies against a wide range of EV71 strains of various genotypes. The study showed that between laboratory variations in neutralization titres were significantly reduced when values were expressed relative to those of either of the two candidate sera. Sample 14/140 was established as the WHO 1st International Standard for anti-EV71 serum (human), 14/138 as its potential replacement and 13/238 as a WHO Reference Reagent, with assigned unitage of 1,000, 1090 and 300 International Units (IU) of anti-EV71 neutralizing antibodies per ampoule, respectively.
Gillian Cooper; Qunying Mao; Laura Crawt; Yiping Wang; Thomas Dougall; Peter Rigsby; Zhenglun Liang; Miao Xu; Philip Minor; Junzhi Wang; Javier Martin; The Collaborative Study Group. Establishment of the 1st WHO International Standard for anti-EV71 serum (Human). Biologicals 2018, 53, 39 -50.
AMA StyleGillian Cooper, Qunying Mao, Laura Crawt, Yiping Wang, Thomas Dougall, Peter Rigsby, Zhenglun Liang, Miao Xu, Philip Minor, Junzhi Wang, Javier Martin, The Collaborative Study Group. Establishment of the 1st WHO International Standard for anti-EV71 serum (Human). Biologicals. 2018; 53 ():39-50.
Chicago/Turabian StyleGillian Cooper; Qunying Mao; Laura Crawt; Yiping Wang; Thomas Dougall; Peter Rigsby; Zhenglun Liang; Miao Xu; Philip Minor; Junzhi Wang; Javier Martin; The Collaborative Study Group. 2018. "Establishment of the 1st WHO International Standard for anti-EV71 serum (Human)." Biologicals 53, no. : 39-50.
Enterovirus B69 (EV-B69) is a rarely reported type and till date, only the full-length genome sequence of the prototype strain is available. Besides the prototype strain, only limited VP1 sequences of this virus from Africa and India are available in GenBank. In this study, we analyzed the full-length genome sequence of an EV-B69 strain recovered from a patient with acute flaccid paralysis in Niger. Compared with the EV-B69 prototype strain, it had 79.6% and 76.3% nucleotide identity in the complete genome and VP1 coding region, respectively. VP1 sequence analyses revealed also high variation in nucleotide similarity (68.9%–82.8%) with previously isolated EV-B69 strains in India and Africa. The great genetic divergence among EV-B69 strains indicates that this type is not a newly emergent virus, but has circulated for many years at low epidemic strength. Phylogenetic incongruity between structural and non-structural regions and similarity plot analyses revealed that multiple recombination events occurred during its evolution. This study expands the number of EV-B69 whole genome sequences which would help genomic comparison for future studies to understand the biological and pathogenic properties of this virus, assess its potential public health impact and comprehend the role of recombination in the evolution of enteroviruses.
Maria Dolores Fernandez-Garcia; Manasi Majumdar; Ousmane Kebe; Kader Ndiaye; Javier Martin. Identification and whole-genome characterization of a recombinant Enterovirus B69 isolated from a patient with Acute Flaccid Paralysis in Niger, 2015. Scientific Reports 2018, 8, 1 -8.
AMA StyleMaria Dolores Fernandez-Garcia, Manasi Majumdar, Ousmane Kebe, Kader Ndiaye, Javier Martin. Identification and whole-genome characterization of a recombinant Enterovirus B69 isolated from a patient with Acute Flaccid Paralysis in Niger, 2015. Scientific Reports. 2018; 8 (1):1-8.
Chicago/Turabian StyleMaria Dolores Fernandez-Garcia; Manasi Majumdar; Ousmane Kebe; Kader Ndiaye; Javier Martin. 2018. "Identification and whole-genome characterization of a recombinant Enterovirus B69 isolated from a patient with Acute Flaccid Paralysis in Niger, 2015." Scientific Reports 8, no. 1: 1-8.
During the 2014–2015 outbreak of Ebola virus disease in Guinea, 13 type 2 circulating vaccine-derived polioviruses (cVDPVs) were isolated from 6 polio patients and 7 healthy contacts. To clarify the genetic properties of cVDPVs and their emergence, we combined epidemiologic and virologic data for polio cases in Guinea. Deviation of public health resources to the Ebola outbreak disrupted polio vaccination programs and surveillance activities, which fueled the spread of neurovirulent VDPVs in an area of low vaccination coverage and immunity. Genetic properties of cVDPVs were consistent with their capacity to cause paralytic disease in humans and capacity for sustained person-to-person transmission. Circulation ceased when coverage of oral polio vaccine increased. A polio outbreak in the context of the Ebola virus disease outbreak highlights the need to consider risks for polio emergence and spread during complex emergencies and urges awareness of the challenges in polio surveillance, vaccination, and diagnosis.
Maria Dolores Fernandez Garcia; Manasi Majumdar; Ousmane Kebe; M. Fernandez-Garcia Et Al.; Moussa Kone; Mouctar Kande; Moustapha Dabo; Mohamed Salif Sylla; Djenou Sompare; Wayne Howard; Ousmane Faye; Javier Martin; Kader Ndiaye. Emergence of Vaccine-Derived Polioviruses during Ebola Virus Disease Outbreak, Guinea, 2014–2015. Emerging Infectious Diseases 2018, 24, 65 -74.
AMA StyleMaria Dolores Fernandez Garcia, Manasi Majumdar, Ousmane Kebe, M. Fernandez-Garcia Et Al., Moussa Kone, Mouctar Kande, Moustapha Dabo, Mohamed Salif Sylla, Djenou Sompare, Wayne Howard, Ousmane Faye, Javier Martin, Kader Ndiaye. Emergence of Vaccine-Derived Polioviruses during Ebola Virus Disease Outbreak, Guinea, 2014–2015. Emerging Infectious Diseases. 2018; 24 (1):65-74.
Chicago/Turabian StyleMaria Dolores Fernandez Garcia; Manasi Majumdar; Ousmane Kebe; M. Fernandez-Garcia Et Al.; Moussa Kone; Mouctar Kande; Moustapha Dabo; Mohamed Salif Sylla; Djenou Sompare; Wayne Howard; Ousmane Faye; Javier Martin; Kader Ndiaye. 2018. "Emergence of Vaccine-Derived Polioviruses during Ebola Virus Disease Outbreak, Guinea, 2014–2015." Emerging Infectious Diseases 24, no. 1: 65-74.
BackgroundEnvironmental surveillance (ES) is a sensitive method for detecting human enterovirus (HEV) circulation and it is used worldwide to support global polio eradication. We describe a novel ES approach using next generation sequencing (NGS) to identify HEVs in sewage samples taken in London, UK, from June-2016 to May-2017.Methods and ResultsTwo different sewage concentration methods were used: a two-phase aqueous separation system and size-exclusion by filtration and centrifugation, in combination with virus isolation in cell cultures and NGS. Type 1 and 3 vaccine-like poliovirus (PV) strains were detected in samples from September 2016 and January 2017. NGS analysis allowed us to rapidly obtain whole-genome sequences of polio and non-polio HEV strains. As many as six virus strains from different HEV serotypes were identified in a single cell culture flask. PV isolates contained only a small number of mutations from vaccine strains commonly seen in early isolates from vaccinees.ConclusionsOur ES setup has high sensitivity for polio and non-polio HEV detection generating nearly whole-genome sequence information. Such ES systems provide critical information to assist the polio eradication endgame and contribute to improve our understanding of HEV circulation patterns in humans.
Manasi Majumdar; Dimitra Klapsa; Thomas Wilton; Joyce Odeke Akello; Catherine Anscombe; David Allen; Edward T Mee; Philip D Minor; Javier Martin. Isolation of Vaccine-Like Poliovirus Strains in Sewage Samples From the United Kingdom. Journal of Infectious Diseases 2017, 217, 1222 -1230.
AMA StyleManasi Majumdar, Dimitra Klapsa, Thomas Wilton, Joyce Odeke Akello, Catherine Anscombe, David Allen, Edward T Mee, Philip D Minor, Javier Martin. Isolation of Vaccine-Like Poliovirus Strains in Sewage Samples From the United Kingdom. Journal of Infectious Diseases. 2017; 217 (8):1222-1230.
Chicago/Turabian StyleManasi Majumdar; Dimitra Klapsa; Thomas Wilton; Joyce Odeke Akello; Catherine Anscombe; David Allen; Edward T Mee; Philip D Minor; Javier Martin. 2017. "Isolation of Vaccine-Like Poliovirus Strains in Sewage Samples From the United Kingdom." Journal of Infectious Diseases 217, no. 8: 1222-1230.
Individuals with primary immunodeficiency disorder may excrete poliovirus for extended periods and will constitute the only remaining reservoir of virus after eradication and withdrawal of oral poliovirus vaccine. Here, we analyzed the epidemiology of prolonged and chronic immunodeficiency-related vaccine-derived poliovirus cases in a registry maintained by the World Health Organization, to identify risk factors and determine the length of excretion. Between 1962 and 2016, there were 101 cases, with 94/101 (93%) prolonged excretors and 7/101 (7%) chronic excretors. We documented an increase in incidence in recent decades, with a shift toward middle-income countries, and a predominance of poliovirus type 2 in 73/101 (72%) cases. The median length of excretion was 1.3 years (95% confidence interval: 1.0, 1.4) and 90% of individuals stopped excreting after 3.7 years. Common variable immunodeficiency syndrome and residence in high-income countries were risk factors for long-term excretion. The changing epidemiology of cases, manifested by the greater incidence in recent decades and a shift to from high- to middle-income countries, highlights the expanding risk of poliovirus transmission after oral poliovirus vaccine cessation. To better quantify and reduce this risk, more sensitive surveillance and effective antiviral therapies are needed.
Grace Macklin; Yi Liao; Marina Takane; Kathleen Dooling; Stuart Gilmour; Ondrej Mach; Olen M. Kew; Roland W. Sutter; The iVDPV Working Group; Ousmane Diop; Nicksy Gumede Moeletsi; Raffaella Williams; Mohamed Seghier; Francis Delpeyroux; Gloria Rey Benito; Maria Cecilia Freire; Cara Burns; Humayun Asghar; Salman Sharif; Jagadish Deshpande; Shohre Shahmahmoodi; Henda Triki; Laila E Bassioni; Amina Al-Jardani; Eugene Merav Weil Gavrilin; Javier Martin; Sirima Pattamadilok; Sunethra Gunasena; Yan Zhang; Wenbo Xu. Prolonged Excretion of Poliovirus among Individuals with Primary Immunodeficiency Disorder: An Analysis of the World Health Organization Registry. Frontiers in Immunology 2017, 8, 1103 .
AMA StyleGrace Macklin, Yi Liao, Marina Takane, Kathleen Dooling, Stuart Gilmour, Ondrej Mach, Olen M. Kew, Roland W. Sutter, The iVDPV Working Group, Ousmane Diop, Nicksy Gumede Moeletsi, Raffaella Williams, Mohamed Seghier, Francis Delpeyroux, Gloria Rey Benito, Maria Cecilia Freire, Cara Burns, Humayun Asghar, Salman Sharif, Jagadish Deshpande, Shohre Shahmahmoodi, Henda Triki, Laila E Bassioni, Amina Al-Jardani, Eugene Merav Weil Gavrilin, Javier Martin, Sirima Pattamadilok, Sunethra Gunasena, Yan Zhang, Wenbo Xu. Prolonged Excretion of Poliovirus among Individuals with Primary Immunodeficiency Disorder: An Analysis of the World Health Organization Registry. Frontiers in Immunology. 2017; 8 ():1103.
Chicago/Turabian StyleGrace Macklin; Yi Liao; Marina Takane; Kathleen Dooling; Stuart Gilmour; Ondrej Mach; Olen M. Kew; Roland W. Sutter; The iVDPV Working Group; Ousmane Diop; Nicksy Gumede Moeletsi; Raffaella Williams; Mohamed Seghier; Francis Delpeyroux; Gloria Rey Benito; Maria Cecilia Freire; Cara Burns; Humayun Asghar; Salman Sharif; Jagadish Deshpande; Shohre Shahmahmoodi; Henda Triki; Laila E Bassioni; Amina Al-Jardani; Eugene Merav Weil Gavrilin; Javier Martin; Sirima Pattamadilok; Sunethra Gunasena; Yan Zhang; Wenbo Xu. 2017. "Prolonged Excretion of Poliovirus among Individuals with Primary Immunodeficiency Disorder: An Analysis of the World Health Organization Registry." Frontiers in Immunology 8, no. : 1103.
The poliovirus vaccine field is moving towards novel vaccination strategies. Withdrawal of the Oral Poliovirus Vaccine and implementation of the conventional Inactivated Poliovirus Vaccine (cIPV) is imminent. Moreover, replacement of the virulent poliovirus strains currently used for cIPV with attenuated strains is preferred. We generated Cold-Adapted Viral Attenuation (CAVA) poliovirus strains by serial passage at low temperature and subsequent genetic engineering, which contain the capsid sequences of cIPV strains combined with a set of mutations identified during cold-adaptation. These viruses displayed a highly temperature sensitive phenotype with no signs of productive infection at 37°C as visualized by electron microscopy. Furthermore, decreases in infectious titers, viral RNA, and protein levels were measured during infection at 37°C, suggesting a block in the viral replication cycle at RNA replication, protein translation, or earlier. However, at 30°C, they could be propagated to high titers (9.4–9.9 Log10TCID50/ml) on the PER.C6 cell culture platform. We identified 14 mutations in the IRES and non-structural regions, which in combination induced the temperature sensitive phenotype, also when transferred to the genomes of other wild-type and attenuated polioviruses. The temperature sensitivity translated to complete absence of neurovirulence in CD155 transgenic mice. Attenuation was also confirmed after extended in vitro passage at small scale using conditions (MOI, cell density, temperature) anticipated for vaccine production. The inability of CAVA strains to replicate at 37°C makes reversion to a neurovirulent phenotype in vivo highly unlikely, therefore, these strains can be considered safe for the manufacture of IPV. The CAVA strains were immunogenic in the Wistar rat potency model for cIPV, inducing high neutralizing antibody titers in a dose-dependent manner in response to D-antigen doses used for cIPV. In combination with the highly productive PER.C6 cell culture platform, the stably attenuated CAVA strains may serve as an attractive low-cost and (bio)safe option for the production of a novel next generation IPV. The vaccines that are used to protect against poliovirus infection have been available since the 1950s and have brought the eradication of poliomyelitis to our doorstep. For the post-eradication era, an Inactivated Poliovirus Vaccine (IPV) based on attenuated Sabin strains is recommended, as these strains are currently the only option to move to safer manufacturing of IPV. Here we describe three novel poliovirus strains that cannot replicate at 37°C. Their lack of pathogenicity was confirmed by intracerebral inoculation of susceptible transgenic mice that subsequently did not develop any symptoms of poliomyelitis. The inability to replicate at 37°C is caused by multiple mutations which do not revert to virulence after passage in cells. Furthermore, when used as vaccines, these viruses were capable of inducing a potent immune response in rats. At low temperature (30°C) these viruses showed high productivity on the PER.C6 cell line, which has the potential to significantly reduce costs of goods, as previously shown for conventional poliovirus strains. Taken together, these new strains could contribute to a safe, genetically stable, efficacious and affordable IPV.
Barbara P. Sanders; Isabel De Los Rios Oakes; Vladimir Van Hoek; Viki Bockstal; Tobias Kamphuis; Taco G. Uil; Yutong Song; Gillian Cooper; Laura E. Crawt; Javier Martin; Roland Zahn; John Lewis; Eckard Wimmer; Jerome H. H. V. Custers; Hanneke Schuitemaker; Jeronimo Cello; Diana Edo-Matas. Cold-Adapted Viral Attenuation (CAVA): Highly Temperature Sensitive Polioviruses as Novel Vaccine Strains for a Next Generation Inactivated Poliovirus Vaccine. PLOS Pathogens 2016, 12, e1005483 .
AMA StyleBarbara P. Sanders, Isabel De Los Rios Oakes, Vladimir Van Hoek, Viki Bockstal, Tobias Kamphuis, Taco G. Uil, Yutong Song, Gillian Cooper, Laura E. Crawt, Javier Martin, Roland Zahn, John Lewis, Eckard Wimmer, Jerome H. H. V. Custers, Hanneke Schuitemaker, Jeronimo Cello, Diana Edo-Matas. Cold-Adapted Viral Attenuation (CAVA): Highly Temperature Sensitive Polioviruses as Novel Vaccine Strains for a Next Generation Inactivated Poliovirus Vaccine. PLOS Pathogens. 2016; 12 (3):e1005483.
Chicago/Turabian StyleBarbara P. Sanders; Isabel De Los Rios Oakes; Vladimir Van Hoek; Viki Bockstal; Tobias Kamphuis; Taco G. Uil; Yutong Song; Gillian Cooper; Laura E. Crawt; Javier Martin; Roland Zahn; John Lewis; Eckard Wimmer; Jerome H. H. V. Custers; Hanneke Schuitemaker; Jeronimo Cello; Diana Edo-Matas. 2016. "Cold-Adapted Viral Attenuation (CAVA): Highly Temperature Sensitive Polioviruses as Novel Vaccine Strains for a Next Generation Inactivated Poliovirus Vaccine." PLOS Pathogens 12, no. 3: e1005483.