Konstantin Chumakov's research while affiliated with U.S. Food and Drug Administration and other places
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Publications (139)
Recently, genetically stable novel OPVs (nOPV) were developed by modifying the ge-nomes of Sabin viruses of conventional OPVs to reduce the risk of reversion to neurovirulence and therefore the risk of generating circulating vaccine-derived polioviruses. There is a need for specific and sensitive methods for the identification and quantification of...
Trained immunity is a long-term increase in responsiveness of innate immune cells, induced by certain infections and vaccines. During the last 3 years of the COVID-19 pandemic, vaccines that induce trained immunity, such as BCG, MMR, OPV, and others, have been investigated for their capacity to protect against COVID-19. Further, trained immunity-in...
Inactivated Polio Vaccines (IPV) and live Oral Polio Vaccine (OPV) were introduced in the mid-20th century, and their coordinated worldwide use led to almost complete elimination of the disease, with only one serotype of poliovirus remaining endemic in just two countries. Polio eradication will lead to discontinuation of OPV use and its replacement...
Background:
Poliovirus post-eradication containment of wild-type 2 poliovirus (PV2) requires the destruction of all materials containing, or potentially containing, PV2. Acute flaccid paralysis (AFP) cases in Israel between 1973 and 1988 were caused by all three serotypes; thus, isolates from cases and case-contacts were either PV2 or potentially...
Background
Sabin strains used in oral poliovirus vaccines (OPV) can revert to virulence and, in rare instances, cause disease or generate vaccine-derived strains leading to outbreaks in areas of low immunisation coverage. A novel OPV2 (nOPV2) was designed to stabilise the viral genome against reversion and reduce recombination events that might lea...
Introduction
Recent reviews summarize evidence that some vaccines have heterologous or non-specific effects (NSE), potentially offering protection against multiple pathogens. Numerous economic evaluations examine vaccines' pathogen-specific effects, but less than a handful focus on NSE. This paper addresses that gap by reporting economic evaluation...
Emergence of mutations is an inherent property of RNA viruses with several implications
for their replication, pathogenesis, and evolutionary adaptation. Oral poliovirus vaccine (OPV), developed by Albert Sabin, is composed of live attenuated polioviruses of three serotypes that can revert to neurovirulence during replication in cell culture and in...
Background
The live vaccines bacille Calmette-Guérin (BCG) and measles vaccine have beneficial non-specific effects (NSEs) reducing mortality more than can be explained by prevention of tuberculosis or measles infection. Live oral polio vaccine (OPV) will be stopped after polio eradication, we therefore reviewed the potential NSEs of OPV.
Methods...
Background
Effective response to emerging pandemic threats is complicated by the need to develop specific vaccines and other medical products. The availability of broadly specific countermeasures that could be deployed early in the pandemic could significantly alter its course and save countless lives. Live attenuated vaccines (LAVs) were shown to...
Background
Several live attenuated vaccines were shown to provide temporary protection against a variety of infectious diseases through stimulation of the host innate immune system.
Objective
To test the hypothesis that countries using oral polio vaccine (OPV) have a lower cumulative number of cases diagnosed with COVID-19 per 100,000 population (...
Novel oral poliovirus vaccine type 2 (nOPV2) is being developed to reduce the rare occurrence of disease and outbreaks associated with the genetic instability of the Sabin vaccine strains. Children aged 1 to 5 years were enrolled in two related clinical studies to assess safety, immunogenicity, shedding rates and properties of the shed virus follow...
Background
Recent reviews summarize evidence that some vaccines have heterologous or non-specific effects (NSE), potentially offering protection against multiple pathogens. Numerous economic evaluations examine vaccines’ pathogen-specific effects, but we have found only two economic evaluations of NSE. This paper starts to fill this gap by reportin...
One of the ideas for lessening Zika pathogenicity is the addition of its natural or engineered defective virus genomes (DVGs) (have no pathogenicity) to the infection pool: a DVG is redirecting the wild-type (WT)-associated virus development resources toward its own maturation. The mathematical model presented here, attuned to the data from interpl...
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 vaccin...
To control circulating vaccine-derived type 2 poliovirus outbreaks, a more genetically stable novel Oral Poliovirus Vaccine type 2 (nOPV2) was developed by targeted modifications of Sabin 2 genome. Since the use of OPV2 made of Sabin 2 strain has been stopped, it is important to exclude the possibility that batches of nOPV2 are contaminated with Sa...
Evaluation and validation of next-generation sequencing to support lot release for a novel type 2 oral poliovirus vaccine, Vaccine: X (2021), doi: https://doi. States g P.T. Bio Farma, Bandung, Indonesia Evaluation and validation of next-generation sequencing to support lot release for a novel type 2 oral poliovirus vaccine ABSTRACT A novel, geneti...
The Global Polio Eradication Initiative, launched in 1988 with anticipated completion by 2000, has yet to reach its ultimate goal. The recent surge of polio cases urgently calls for a reassessment of the programme's current strategy and a new design for the way forward. We propose that the sustainable protection of the world population against para...
A novel, genetically-stabilized type 2 oral polio vaccine (nOPV2), developed to assist in the global polio eradication program, was recently the first-ever vaccine granted Emergency Use Listing by the WHO. Lot release tests for this vaccine included—for the first time to our knowledge—the assessment of genetic heterogeneity using next-generation se...
The COVID-19 pandemic triggered an unparalleled pursuit of vaccines to induce specific adaptive immunity, based on virus-neutralizing antibodies and T cell responses. Although several vaccines have been developed just a year after SARS-CoV-2 emerged in late 2019, global deployment will take months or even years. Meanwhile, the virus continues to ta...
Recognition of Zika virus (ZIKV) sexual transmission (ST) among humans challenges our understanding of the maintenance of mosquito-borne viruses in nature. Here we dissected the relative contributions of the components of male reproductive system (MRS) during early male-to-female ZIKV transmission by utilizing mice with altered antiviral responses,...
Enormous progress has been made in global efforts to eradicate poliovirus, using live-attenuated Sabin oral poliovirus vaccine (OPV). However, as the incidence of disease due to wild poliovirus has declined, vaccine-derived poliovirus (VDPV) has emerged in areas of low-vaccine coverage. Coordinated global cessation of routine, type 2 Sabin OPV (OPV...
Live vaccines can prevent unrelated infections and may temporarily protect against COVID-19
Background: Next generation sequencing (NGS) analysis was compared to the current MAPREC (mutational analysis by PCR and restriction enzyme cleavage) assay for the quality control of live-attenuated oral polio vaccine (OPV).
Methods: MAPREC measures reversion of the main OPV attenuating mutations such as uracil (U) to cytosine (C) at nucleotide 47...
Background:
Next generation sequencing (NGS) analysis was compared to the current MAPREC (mutational analysis by PCR and restriction enzyme cleavage) assay for the quality control of live-attenuated oral polio vaccine (OPV).
Methods:
MAPREC measures reversion of the main OPV attenuating mutations such as uracil (U) to cytosine (C) at nucleotide...
Determination of poliovirus-neutralizing antibodies is an important part of clinical studies of poliovirus vaccines, epidemiological surveillance and seroprevalence studies that are crucial for global polio eradication campaigns. The conventional neutralization test is based on inhibition of cytopathic effect caused by poliovirus by serial dilution...
Poliovirus (PV)-specific intestinal IgAs are important for cessation of PV shedding in the gastrointestinal tract following an acute infection with wild type or vaccine-derived PV strains. We sought to produce IgA monoclonal antibodies (mAbs) with PV neutralizing activity. We first performed de novo IgA discovery from primary human B cells using a...
A concerted action on the part of international agencies and national governments has resulted in the near-eradication of poliomyelitis. However, both the oral polio vaccine (OPV) and the inactivated polio vaccine (IPV) have deficiencies which make them suboptimal for use after global eradication. OPV is composed of attenuated Sabin strains and sti...
To address the biosafety and biosecurity concerns related to the manufacture of inactivated polio vaccine (IPV), several manufacturers started producing it from attenuated Sabin strains. Slight immunological differences between wild and attenuated strains create a challenge for testing IPV potency, which is defined as the content of protective D-an...
Background:
Conventional assays to titrate polioviruses usually test serial dilutions inoculated into replicate cell cultures to determine a 50% cytopathic endpoint, a process that is both time-consuming and laborious. Such a method is still used to measure potency of live Oral Poliovirus Vaccine during vaccine development and production and in so...
Hybridoma methods for monoclonal antibody (mAb) cloning are a mainstay of biomedical research, but they are hindered by the need to maintain hybridomas in oligoclonal pools during antibody screening. Here, we describe a system in which hybridomas specifically capture and display the mAbs they secrete: On-Cell mAb Screening (OCMS™). In OCMS™, mAbs d...
The poliovirus eradication initiative has spawned global immunization infrastructure and dramatically decreased the prevalence of the disease, yet the original virus eradication goal has not been met. The suboptimal properties of the existing vaccines are among the major reasons why the program has repeatedly missed eradication deadlines. Oral live...
Bovine viral diarrhoea virus (BVDV) is a cattle pathogen that has previously been reported to be present in bovine raw materials used in the manufacture of biological products for human use. Seven lots of trivalent measles, mumps and rubella (MMR) vaccine and 1 lot of measles vaccine from the same manufacturer, together with 17 lots of foetal bovin...
An improved quantitative multiplex one-step RT-PCR (qmosRT-PCR) for simultaneous identification and quantitation of all three serotypes of poliovirus is described. It is based on using serotype-specific primers and fluorescent TaqMan oligonucleotide probes. The assay can be used for high-throughput screening of samples for the presence of polioviru...
Deep sequencing was used to determine complete nucleotide sequences of echovirus 11 (EV11) strains isolated from a chronically infected patient with CVID as well as from cases of acute enterovirus infection. Phylogenetic analysis showed that EV11 strains that circulated in Israel in 1980-90s could be divided into four clades. EV11 strains isolated...
A list of EV11 isolates used for whole-genome deep sequencing and their origin.
(DOCX)
Amino acid differences in iEV11 relative to the closest Genogroup A isolate A01-EV11-5789 cEV-11.
(DOCX)
Frequency of EV11 isolation in Israel by year.
(TIF)
According to manufacturers, inactivated poliovirus vaccines (IPVs) are freeze sensitive and require storage between 2°C and 8°C, whereas oral poliovirus vaccine requires storage at −20 °C. Introducing IPV into ongoing immunization services might result in accidental exposure to freezing temperatures and potential loss of vaccine potency. To better...
Complete genomic sequences of a non-redundant set of 70 recombinants between three serotypes of attenuated Sabin polioviruses as well as location (based on partial sequencing) of crossover sites of 28 additional recombinants were determined and compared with the previously published data. It is demonstrated that the genomes of Sabin viruses contain...
Sequence heterogeneity is a common characteristic of RNA viruses that is often referred to as sub-populations or quasispecies. Traditional techniques used for assembly of short sequence reads produced by deep sequencing, such as de-novo assemblers, ignore the underlying diversity. Here, we introduce a novel algorithm that simultaneously assembles d...
Enteroviruses (EVs) causing persisting infection are characterized by minimal replication and genetic changes. Typing of these agents may complement disease assessment and shed light on pathogenesis. Here we report an integrated approach for EV detection in human samples that is based on pre-enrichment of virus in cell culture before search for the...
Despite a great deal of prior research, the early pathogenic events in natural oral poliovirus infection remain poorly defined. To establish a model for study, we infected 39 macaques by feeding them single high doses of the virulent Mahoney strain of wild type 1 poliovirus. Doses ranging from 10⁷ to 10⁹ 50% tissue culture infective doses (TCID50)...
Advances in high-throughput sequencing (HTS) technologies have greatly increased the availability of genomic data and potential discovery of clinically significant genomic variants. However, numerous issues still exist with the analysis of these data, including data complexity, the absence of formally agreed upon best practices, and inconsistent re...
Growth kinetics of ZIKV-wt and ZIKV-NS3m viruses in different cell lines. Growth kinetics of ZIKV-wt and ZIKV-NS3m in Huh7, C6/36, human foreskin fibroblast, human neuroblastoma SH-SY5Y, mouse testis-derived Sertoli 15P-1, human trophoblast HTR-8/Neo, and human placenta-derived BeWo, JEG-3, and JAR cells. Each cell line was infected at an MOI of 0....
Unlabelled:
An arthropod-borne virus, Zika virus (ZIKV), has recently emerged as a major human pathogen. Associated with complications during perinatal development and Guillain-Barré syndrome in adults, ZIKV raises new challenges for understanding the molecular determinants of flavivirus pathogenesis. This underscores the necessity for the develop...
Mutational profile of ZIKV-ICD genome. Positions within the ZIKV-ICD genome that contained single nucleotide polymorphisms (SNPs) at frequencies above 1% of quality-filtered reads are indicated, along with the corresponding amino acid substitutions.
Amino acid differences between Paraiba_01/2015 and ZIKV strains associated with human congenital microcephaly.
Mutational profile of ZIKV-NS3m genome. Positions within the ZIKV-NS3m genome that contained single nucleotide polymorphisms (SNPs) at frequencies above 1% of quality-filtered reads are indicated, along with the corresponding amino acid substitutions.
An arthropod-borne virus, Zika virus (ZIKV), has recently emerged as a major human pathogen. Associated with complications during perinatal development and Guillain-Barré syndrome in adults, ZIKV raises new challenges for understanding the molecular determinants of flavivirus pathogenesis. This underscores the necessity for the development of a rev...
Mutational profile of ZIKV-wt genome. Positions within the ZIKV-wt genome that contained single nucleotide polymorphisms (SNPs) at frequencies above 1% of quality-filtered reads are indicated, along with the corresponding amino acid substitutions. “Informative” denotes sites that provide information for phylogenetic construction; “Uninformative” de...
The WHO recommends complete withdrawal of Oral Polio Vaccine (OPV) Type 2 by April 2016 globally and replacing with at least one dose of Inactivated Poliovirus Vaccine (IPV). However, high-cost, limited supply of IPV, persistent circulating vaccine-derived polioviruses transmission and need for subsequent boosters remain unresolved. To meet this cr...
An approach is proposed for environmental surveillance of poliovirus by concentrating sewage samples with tangential flow filtration (TFF) followed by deep sequencing of viral RNA. Subsequent to testing the method with samples from Finland, samples from Pakistan, a country endemic for poliovirus, were investigated. Genomic sequencing was either per...
The High-performance Integrated Virtual Environment (HIVE) is a distributed storage and compute environment designed primarily to handle next-generation sequencing (NGS) data. This multicomponent cloud infrastructure provides secure web access for authorized users to deposit, retrieve, annotate and compute on NGS data, and to analyse the outcomes u...
Neutralizing antibodies induced by vaccination or natural infection play a critically important role in protection against the viral diseases. In general, neutralization of the viral infection occurs via two major pathways: pre- and post-attachment modes, the first being the most important for such infections as influenza and polio, the latter bein...
Comparing fADI VAI and fADI 50% titers determined in the manual and automated fADI experiments.
a, b, c: VAI data determined at dilution 1:1000. d, e, f; fADI 50% titers calculated from the VAI data.
(TIF)
Comparing fADI for NHP sera challenged with filoviruses and sera from human recipients immunized with influenza.
Panel a: fADI for NHP sera challenged with Ebola Zaire (blue bars–pre-challenged serum; red bar–post-challenge serum, Marburg Musoke (green bars—pre-challenged serum; purple bars–post-challenge serum). Panel b: fADI for sera from human r...
Theoretical fADI titration curves for strong and weak sera.
Serum A is supposedly weak. Serum B is supposedly strong. For both weak and strong sera, the shapes of the titration curves are supposed to be similar. Red curve shows the titration curve symmetrized mathematically to center at Log(dilution) = 0 (i.e., a serum is undiluted).
(TIF)
Comparing fADI and HAI data for sera from human recipients immunized with seasonal influenza vaccine in 2009.
Panel a: fADI and HAI data for New Caledonia H1N1 virus. Panel b: fADI and HAI data for Wisconsin H3N2 virus. Both fADI and HAI data shown as 50% titer values.
(TIF)
Stepwise determination of the symmetrized titration curve for polio fADI.
a: Step 1, plotting a few primary VAI data against dilution factor; b; Step 2, re-plotting the primary VAI data in semi-Log coordinates; c: Step 3, adding VAI data from other measurements, re-plotting; d: Step 4, fitting a sigmoidal regression curve to the plotted VAI data us...
Transfer of the single point VAI data into fADI 50% titers using the symmetrized titration curve.
a: VAI data determined for Polio 1 at dilutions 1:250 and 1:1000. b; fADI 50% titers calculated from the VAI data.
(TIF)