scholarly journals Advax-CpG Adjuvant Provides Antigen Dose-Sparing and Enhanced Immunogenicity for Inactivated Poliomyelitis Virus Vaccines

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 500
Author(s):  
Yoshikazu Honda-Okubo ◽  
Jeremy Baldwin ◽  
Nikolai Petrovsky
Keyword(s):  
Neutralizing Antibodies ◽  
Serum Antibody ◽  
Oral Polio Vaccine ◽  
Antigen Dose ◽  
Polio Vaccine ◽  
Antibody Titers ◽  
Dose Sparing ◽  
Sparing Effect ◽  
Eradicate Polio

Global immunization campaigns have resulted in a major decline in the global incidence of polio cases, with wild-type poliovirus remaining endemic in only two countries. Live oral polio vaccine (OPV) played a role in the reduction in polio case numbers; however, the risk of OPV developing into circulating vaccine-derived poliovirus makes it unsuitable for eradication programs. Trivalent inactivated polio virus (TIPV) vaccines which contain formalin-inactivated antigens produced from virulent types 1, 2 and 3 reference polio strains grown in Vero monkey kidney cells have been advocated as a replacement for OPV; however, TIPVs have weak immunogenicity and multiple boosts are required before peak neutralizing titers are reached. This study examined whether the incorporation of the novel polysaccharide adjuvant, Advax-CpG, could boost the immunogenicity of two TIPV vaccines, (i) a commercially available polio vaccine (IPOL®, Sanofi Pasteur) and (ii) a new TIPV formulation developed by Statens Serum Institut (SSI). Mice were immunized intramuscularly based on recommended vaccine dosage schedules and serum antibody titers were followed for 12 months post-immunization. Advax-CpG significantly enhanced the long-term immunogenicity of both TIPV vaccines and had at least a 10-fold antigen dose-sparing effect. An exception was the poor ability of the SSI TIPV to induce serotype type 1 neutralizing antibodies. Immunization with monovalent IPVs suggested that the low type 1 response to TIPV may be due to antigen competition when the type 1 antigen was co-formulated with the type 2 and 3 antigens. This study provides valuable insights into the complexity of the formulation of multivalent polio vaccines and supports the further development of adjuvanted antigen-sparing TIPV vaccines in the fight to eradicate polio.

scholarly journals Immunogenicity of Oral Polio Vaccine and Salk Inactive Polio Vaccine Against Xinjiang Imported Type 1 Wild Poliovirus

2019 ◽  
Vol 70 (9) ◽  
pp. 1980-1984 ◽  
Author(s):  
Dongmei Yan ◽  
Dongyan Wang ◽  
Shuangli Zhu ◽  
Yong Zhang ◽  
Xiaolei Li ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Oral Polio Vaccine ◽  
Neutralizing Antibody ◽  
Genomic Sequencing ◽  
Outbreak Response ◽  
Local Immunity ◽  
Wild Poliovirus ◽  
Polio Vaccine ◽  
Antibody Titers

Abstract Background An outbreak of an imported Type 1 wild poliovirus from Pakistan occurred in the Xinjiang Uygur Autonomous Region of China in 2011, although the local immunity status of the oral polio vaccine (OPV) was relatively satisfied. Methods Neutralizing antibody titers against the Xinjiang strain and Sabin 1 strain were measured in 237 sera from 3 groups of fully OPV-vaccinated persons and 1 group of infants fully vaccinated with the inactive polio vaccine (IPV). Additionally, 17 sera collected from 1 Xinjiang poliomyelitis case and his 16 contacts were also tested. Genomic sequencing was conducted the Xinjiang strain. Results The antibody titers against the Xinjiang strain in each of 237 sera were significantly lower than those against the Sabin 1 strain. Notably, 40.0% of children in Group 1 were seronegative against the Xinjiang strain, which indicated that they might play an important role in wild poliovirus transmission, although their antibody titers against the Sabin 1 strain varied between 1:8 and 1:512. Meanwhile, serological results of the Xinjiang poliomyelitis case and his contacts also provided evidence that a proportion of OPV-vaccinated children had indeed been involved in the transmission chain of the Xinjiang outbreak. Genomic sequencing indicated that the Xinjiang strain was greatly distinguishable from the Sabin 1 strain in neutralizing antigenic sites. Conclusion The lack of neutralizing antibodies against the Xinjiang strain in persons vaccinated by OPV may be associated with the transmission of Type 1 wild poliovirus in Xinjiang. Using Salk IPV along with OPV might be considered in a wild poliovirus outbreak response, especially in the countries which continued to have persistent wild poliovirus circulation.

scholarly journals Inferring Numbers of Wild Poliovirus Excretors Using Quantitative Environmental Surveillance

Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 870
Author(s):  
Yuri Perepliotchikov ◽  
Tomer Ziv-Baran ◽  
Musa Hindiyeh ◽  
Yossi Manor ◽  
Danit Sofer ◽  
...  
Keyword(s):  
Oral Polio Vaccine ◽  
Turnaround Time ◽  
Quantitative Detection ◽  
Environmental Surveillance ◽  
Wild Poliovirus ◽  
Polio Vaccine ◽  
Kinetic Information ◽  
Using Data ◽  
Number Of Individuals

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.

scholarly journals Excretion of Wild-Type and Vaccine-Derived Poliovirus in the Feces of Poliovirus Receptor-Transgenic Mice

2003 ◽  
Vol 77 (11) ◽  
pp. 6541-6545 ◽  
Author(s):  
Hein J. Boot ◽  
Daniella T. J. Kasteel ◽  
Anne-Marie Buisman ◽  
Tjeerd G. Kimman
Keyword(s):  
Transgenic Mice ◽  
Oral Polio Vaccine ◽  
Fecal Excretion ◽  
Wild Type ◽  
Genetic Determinants ◽  
Poliovirus Type ◽  
Oral Transmission ◽  
Polio Vaccine ◽  
Poliovirus Receptor

ABSTRACT The emergence of circulating vaccine-derived poliovirus (cVDPV) strains in suboptimally vaccinated populations is a serious threat to the global poliovirus eradication. The genetic determinants for the transmissibility phenotype of polioviruses, and in particularly of cVDPV strains, are currently unknown. Here we describe the fecal excretion of wild-type poliovirus, oral polio vaccine, and cVDPV (Hispaniola) strains after intraperitoneal injection in poliovirus receptor-transgenic mice. Both the pattern and the level of fecal excretion of the cVDPV strains resemble those of wild-type poliovirus type 1. In contrast, very little poliovirus was present in the feces after oral polio vaccine administration. This mouse model will be helpful in elucidating the genetic determinants for the high fecal-oral transmission phenotype of cVDPV strains.

Long-Lasting Poliovirus-Neutralizing Antibodies among Argentinean Population Immunized with Four Or Five Oral Polio Vaccine Doses 1 Month to 19 Years Previously

2007 ◽  
Vol 20 (1) ◽  
pp. 3-10 ◽  
Author(s):  
Silvia V. Nates ◽  
Laura C. Martinez ◽  
Patricia A. Barril ◽  
Leonardo J. Ferreyra ◽  
Miguel O. Giordano ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Oral Polio Vaccine ◽  
Polio Vaccine

Comparison of Injected and Oral Polio Vaccine for Booster Immunization During the 1979 Polio Outbreak in Lancaster County, Pennsylvania

1981 ◽  
Vol 2 (5) ◽  
pp. 377-379
Author(s):  
Robert G. Doe ◽  
Bruce Kleger ◽  
John L. Randall
Keyword(s):  
Booster Vaccination ◽  
Oral Polio Vaccine ◽  
Neutralizing Antibody ◽  
Igg Antibody ◽  
Booster Immunization ◽  
Lancaster County ◽  
Polio Vaccine ◽  
Before And After ◽  
Antibody Titers ◽  
Better Than

AbstractDuring a 1979 outbreak of poliomyelitis in Lancaster County, Pennsylvania, we investigated the neccessity for and the response to booster vaccination of hospital personnel. The immune response of hospital employees who received booster injections of Salk vaccine (n=38) was compared with that of residents in the surrounding community who received Sabin trivalent OPV boosters (n=43). Serum neutralizing antibody titers to the three polio serotypes were measured before and after booster immunization. Results indicated that 38% of the subjects in both groups had low initial antibody titers. Salk vaccine was in all circumstances as effective or better than Sabin vaccine in increasing neutralizing IgG antibody titers [Infect Control 1981; 2(5):377-379.]

scholarly journals Structural basis for antibody binding to adenylate cyclase toxin reveals RTX linkers as neutralization-sensitive epitopes

2021 ◽  
Vol 17 (9) ◽  
pp. e1009920
Author(s):  
Jory A. Goldsmith ◽  
Andrea M. DiVenere ◽  
Jennifer A. Maynard ◽  
Jason S. McLellan
Keyword(s):  
Adenylate Cyclase ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Structural Data ◽  
Antibody Binding ◽  
Structural Basis ◽  
Antibody Titers ◽  
Adenylate Cyclase Toxin ◽  
Blocking Antibodies

RTX leukotoxins are a diverse family of prokaryotic virulence factors that are secreted by the type 1 secretion system (T1SS) and target leukocytes to subvert host defenses. T1SS substrates all contain a C-terminal RTX domain that mediates recruitment to the T1SS and drives secretion via a Brownian ratchet mechanism. Neutralizing antibodies against the Bordetella pertussis adenylate cyclase toxin, an RTX leukotoxin essential for B. pertussis colonization, have been shown to target the RTX domain and prevent binding to the αMβ2 integrin receptor. Knowledge of the mechanisms by which antibodies bind and neutralize RTX leukotoxins is required to inform structure-based design of bacterial vaccines, however, no structural data are available for antibody binding to any T1SS substrate. Here, we determine the crystal structure of an engineered RTX domain fragment containing the αMβ2-binding site bound to two neutralizing antibodies. Notably, the receptor-blocking antibodies bind to the linker regions of RTX blocks I–III, suggesting they are key neutralization-sensitive sites within the RTX domain and are likely involved in binding the αMβ2 receptor. As the engineered RTX fragment contained these key epitopes, we assessed its immunogenicity in mice and showed that it elicits similar neutralizing antibody titers to the full RTX domain. The results from these studies will support the development of bacterial vaccines targeting RTX leukotoxins, as well as next-generation B. pertussis vaccines.

scholarly journals Intestinal antibody responses to a live oral poliovirus vaccine challenge among adults previously immunized with inactivated polio vaccine in Sweden

2019 ◽  
Vol 4 (4) ◽  
pp. e001613 ◽  
Author(s):  
Elizabeth B Brickley ◽  
Ruth I Connor ◽  
Wendy F Wieland-Alter ◽  
Marc S Collett ◽  
Marianne Hartford ◽  
...  
Keyword(s):  
Limit Of Detection ◽  
Oral Polio Vaccine ◽  
Antibody Responses ◽  
Controlled Clinical Trial ◽  
Inactivated Polio Vaccine ◽  
Poliovirus Type ◽  
Polio Vaccine ◽  
Faecal Samples ◽  
Vaccine Type

BackgroundOur understanding of the acquisition of intestinal mucosal immunity and the control of poliovirus replication and transmission in later life is still emerging.MethodsAs part of a 2011 randomised, blinded, placebo-controlled clinical trial of the experimental antiviral agent pocapavir (EudraCT 2011-004804-38), Swedish adults, aged 18–50 years, who had previously received four doses of inactivated polio vaccine (IPV) in childhood were challenged with a single dose of monovalent oral polio vaccine type 1 (mOPV1). Using faecal samples collected before and serially, over the course of 45 days, after mOPV1 challenge from a subset of placebo-arm participants who did not receive pocapavir (N=12), we investigated the kinetics of the intestinal antibody response to challenge virus by measuring poliovirus type 1-specific neutralising activity and IgA concentrations.ResultsIn faecal samples collected prior to mOPV1 challenge, we found no evidence of pre-existing intestinal neutralising antibodies to any of the three poliovirus serotypes. Despite persistent high-titered vaccine virus shedding and rising serum neutralisation responses after mOPV1 challenge, intestinal poliovirus type 1-specific neutralisation remained low with a titer of ≤18.4 across all time points and individuals. Poliovirus types 1-specific, 2-specific and 3-specific IgA remained below the limit of detection for all specimens collected postchallenge.InterpretationIn contrast to recent studies demonstrating brisk intestinal antibody responses to oral polio vaccine challenge in young children previously vaccinated with IPV, this investigation finds that adults previously vaccinated with IPV have only modest intestinal poliovirus type 1-specific neutralisation and no IgA responses that are measurable in stool samples following documented mOPV1 infection.

scholarly journals Live Respiratory Syncytial Virus Attenuated by M2-2 Deletion and Stabilized Temperature Sensitivity Mutation 1030s Is a Promising Vaccine Candidate in Children

2019 ◽  
Vol 221 (4) ◽  
pp. 534-543 ◽  
Author(s):  
Elizabeth J McFarland ◽  
Ruth A Karron ◽  
Petronella Muresan ◽  
Coleen K Cunningham ◽  
Jennifer Libous ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Temperature Sensitivity ◽  
Neutralizing Antibodies ◽  
Quantitative Polymerase Chain Reaction ◽  
Regulatory Protein ◽  
Serum Antibody ◽  
Respiratory Illness ◽  
Acid Synthesis ◽  
Antibody Titers ◽  
Syncytial Virus

Abstract Background The safety and immunogenicity of live respiratory syncytial virus (RSV) candidate vaccine, LID/ΔM2-2/1030s, with deletion of RSV ribonucleic acid synthesis regulatory protein M2-2 and genetically stabilized temperature-sensitivity mutation 1030s in the RSV polymerase protein was evaluated in RSV-seronegative children. Methods Respiratory syncytial virus-seronegative children ages 6–24 months received 1 intranasal dose of 105 plaque-forming units (PFU) of LID/ΔM2-2/1030s (n = 21) or placebo (n = 11). The RSV serum antibodies, vaccine shedding, and reactogenicity were assessed. During the following RSV season, medically attended acute respiratory illness (MAARI) and pre- and postsurveillance serum antibody titers were monitored. Results Eighty-five percent of vaccinees shed LID/ΔM2-2/1030s vaccine (median peak nasal wash titers: 3.1 log10 PFU/mL by immunoplaque assay; 5.1 log10 copies/mL by reverse-transcription quantitative polymerase chain reaction) and had ≥4-fold rise in serum-neutralizing antibodies. Respiratory symptoms and fever were common (60% vaccinees and 27% placebo recipients). One vaccinee had grade 2 wheezing with rhinovirus but without concurrent LID/ΔM2-2/1030s shedding. Five of 19 vaccinees had ≥4-fold increases in antibody titers postsurveillance without RSV-MAARI, indicating anamnestic responses without significant illness after infection with community-acquired RSV. Conclusions LID/ΔM2-2/1030s had excellent infectivity without evidence of genetic instability, induced durable immunity, and primed for anamnestic antibody responses, making it an attractive candidate for further evaluation.

scholarly journals Wild and vaccine-derived poliovirus circulation, and implications for polio eradication

2016 ◽  
Vol 145 (3) ◽  
pp. 413-419 ◽  
Author(s):  
P. L. LOPALCO
Keyword(s):  
Wild Strain ◽  
Oral Polio Vaccine ◽  
Polio Eradication ◽  
Poliovirus Type ◽  
Polio Vaccine ◽  
Vaccine Schedule ◽  
Long Time ◽  
High Level ◽  
Type 3

SUMMARYPolio cases due to wild virus are reported by only three countries in the world. Poliovirus type 2 has been globally eradicated and the last detection of poliovirus type 3 dates to November 2012. Poliovirus type 1 remains the only circulating wild strain; between January and September 2016 it caused 26 cases (nine in Afghanistan, 14 in Pakistan, three in Nigeria). The use of oral polio vaccine (OPV) has been the key to success in the eradication effort. However, paradoxically, moving towards global polio eradication, the burden caused by vaccine-derived polioviruses (VDPVs) becomes increasingly important. In this paper circulation of both wild virus and VDPVs is reviewed and implications for the polio eradication endgame are discussed. Between April and May 2016 OPV2 cessation has been implemented globally, in a coordinated switch from trivalent OPV to bivalent OPV. In order to decrease the risk for cVDPV2 re-emergence inactivated polio vaccine (IPV) has been introduced in the routine vaccine schedule of all countries. The likelihood of re-emergence of cVDPVs should markedly decrease with time after OPV cessation, but silent circulation of polioviruses cannot be ruled out even a long time after cessation. For this reason, immunity levels against polioviruses should be kept as high as possible in the population by the use of IPV, and both clinical and environmental surveillance should be maintained at a high level.

Sign in / Sign up

Export Citation Format

Share Document