Delving into the Latest Updates on S2/cre5/S15domV/rec1/hifi3(PATH) with Synapse

Overview

Basic Info

Drug Type

Prophylactic vaccine

Synonyms-

Target-

Mechanism

Immunostimulants

Therapeutic Areas

Infectious DiseasesNervous System DiseasesOther Diseases

Active Indication-

Inactive Indication

Poliomyelitis

Originator Organization

Program for Appropriate Technology in Health

Active Organization-

Inactive Organization

Program for Appropriate Technology in Health

Celerion, Inc.

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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A Phase 2, Partial Blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Safety and Immunogenicity of Two Novel Live Attenuated Serotype 2 Oral Poliovirus Vaccines Candidates, in Healthy Adults Previously Vaccinated With Oral Polio Vaccine (OPV) or Inactivated Polio Vaccine (IPV), Compared With Historical Controls Given Sabin OPV2 or Placebo

This study is designed to evaluate the safety and immunogenicity of two novel type 2 oral poliovirus vaccine (nOPV2) candidates (nOPV2 candidate 1 and nOPV2 candidate 2) in adults. The primary objectives of the study include the general safety and immunogenicity of the two candidate vaccines in healthy volunteers previously vaccinated with Sabin monovalent OPV or inactivated polio vaccine (IPV) only.

Start Date22 Oct 2018

Sponsor / Collaborator

University of Antwerp

[+4]

NCT03430349 / CompletedPhase 1

A Phase 1, Blinded, Single Center Study to Evaluate the Safety and Immunogenicity of Two Novel Live Attenuated Serotype 2 Oral Poliovirus Vaccines, Derived From a Modified Sabin 2 Infectious cDNA Clone, in Healthy Adults Previously Primed With Inactivated Polio Vaccine (IPV)

This first-in-human (FIH) phase 1 study is designed to evaluate in contained conditions the safety, immunogenicity, shedding, and genetic stability of two novel oral polio vaccine type 2 (nOPV2) vaccine candidates in IPV-primed adults before testing in a larger adult and adolescent (> 15 y of age) population, and then in young children and infants.

Start Date16 May 2017

Sponsor / Collaborator

University of Antwerp

[+4]

100 Clinical Results associated with S2/cre5/S15domV/rec1/hifi3(PATH)

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100 Translational Medicine associated with S2/cre5/S15domV/rec1/hifi3(PATH)

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100 Patents (Medical) associated with S2/cre5/S15domV/rec1/hifi3(PATH)

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2

Literatures (Medical) associated with S2/cre5/S15domV/rec1/hifi3(PATH)

24 Aug 2022·The Journal of Infectious Diseases

Intestinal Antibody Responses to 2 Novel Live Attenuated Type 2 Oral Poliovirus Vaccines in Healthy Adults in Belgium

Article

Author: Brickley, Elizabeth B ; Arita, Minetaro ; Wieland-Alter, Wendy ; Wright, Peter F ; De Coster, Ilse ; Connor, Ruth I ; Gast, Chris ; Bandyopadhyay, Ananda S ; Ackerman, Margaret E ; Van Damme, Pierre ; Weiner, Joshua A

AbstractIn a blinded phase 1 trial (EudraCT 2017-0000908-21; NCT03430349) in Belgium, healthy adults (aged 18–50 years) previously immunized exclusively with inactivated poliovirus vaccine were administered a single dose of 1 of 2 novel type 2 oral poliovirus vaccines (nOPV2-c1: S2/cre5/S15domV/rec1/hifi3 (n = 15); nOPV2-c2: S2/S15domV/CpG40 (n = 15)) and isolated for 28 days in a purpose-built containment facility. Using stool samples collected near days 0, 14, 21, and 28, we evaluated intestinal neutralization and immunoglobulin A responses to the nOPV2s and found that nOPV2-c1 and nOPV2-c2 induced detectable poliovirus type 2–specific intestinal neutralizing responses in 40.0% and 46.7% of participants, respectively.

01 Jul 2019·The LancetQ1 · MEDICINE

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

Q1 · MEDICINE

Article

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

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.

100 Deals associated with S2/cre5/S15domV/rec1/hifi3(PATH)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Poliomyelitis	Phase 2	BE	Program for Appropriate Technology in Health	22 Oct 2018
Poliomyelitis	Phase 2	BE	Celerion, Inc.	22 Oct 2018

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Clinical Result

Indication

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03430349 (nOPV2M4a, CTgov)	Phase 1	Poliomyelitis	30	Novel OPV2 candidate 1 (Novel OPV2 Candidate 1)	wfuhljeqgn(cadqcfawaj) = fdzitmdpuj zhjyqazzrs (opshoubkva, yvkfpabzpp - uentjmdwak) View more	-	04 Feb 2021
				Novel OPV2 candidate 2 (Novel OPV2 Candidate 2)	wfuhljeqgn(cadqcfawaj) = rgygkkafiz zhjyqazzrs (opshoubkva, gvnxxhfklr - bsjjtlxtwp) View more