nOPV2 Polio Vaccine Clinical Trials, Efficacy, Dosage, Side Effects
The type 2 novel oral polio (nOPV2) vaccine was produced by Indonesia-based PT Biofarma and is derived from the live, infectious virus. It has been 'triple-locked' using genetic engineering to prevent it from becoming harmful and producing a mutation. As a result, nOPV2 is reported to be more genetically stable than previous oral polio vaccines (OPV), with a lower risk of reversion to neurovirulence and less likely to mutate and cause paralysis. The nOPV2 vaccine development began in 2011 and was developed as attenuated serotype two polioviruses derived from a modified Sabin 2 infectious cDNA clone. OPV2 Candidate 1 (S2/cre5/S15domV/rec1/hifi3) and nOPV2 Candidate 2 (S2/S15domV/CpG40) were generated by modifying the Sabin-2 RNA sequence to improve phenotypic stability and make the strains less prone to reversion to virulence.
On November 13, 2020, the nOPV2 vaccine was deployed under the World Health Organization (WHO) Emergency Use Listing procedure (EUL) to enable rapid field availability in countries affected by Circulating vaccine-derived poliovirus type 2 (cVDPV2) outbreaks. The nOPV2 vaccine was WHO-Prequalified in December 2023. The Global Polio Eradication Initiative (GPEI) published nOPV2 Frequently Asked Questions, Fact Sheetsheet, and Global cVDPV outbreak country list. The Global OPV Stockpile Strategy for the period 2022-2026 was published. Using nOPV2 for outbreak response must meet specific requirements under the EUL.
The GPEI has published nOPV2 Safety Monitoring, Management, and Stockpile Strategy guidance manuals. As of October 18, 2024, the nOPV2 vaccine is not U.S. FDA-approved.
nOPV2 Polio Vaccine Breakthrough Cases
The U.S. CDC reported that, from January 2023 to June 2024, cVDPV2 outbreaks were linked to nOPV2 use in 19 countries. These findings highlight that cVDPVs can develop with nOPV2 use when the timing and quality of vaccination responses are suboptimal,
nOPV2 Polio Vaccine Availability 2024
Since the WHO granted emergency use listing in May 2021, approximately 1 billion nOPV2 doses have been administered in more than 35 countries worldwide. The WHO granted prequalification to PT Bio Farma and Biological E. Limited. In 2024, Angola, Kenya, Liberia, the Republic of Sudan, and Uganda launched a nOPV2 vaccination campaign.
nOPV2 Polio Vaccine U.S. CDC
The U.S. CDC Advisory Committee on Immunization Practices (ACIP) presentations on February 28, 2024, included an Introduction and Considerations for the Potential Use of nOPV2 as an Outbreak Control Measure in the U.S. ACIP presentation on October 19, 2022, confirmed the nOPV2 is more genetically stable and less likely to be associated with the emergence of cVDPV2 and can provide mucosal immunity to limit the virus's spreading among IPV-vaccinated people. On September 22, 2023, the CDC reported a preliminary estimate suggesting that cVDPV2 emergencies occur after mOPV2 use at a rate of one emergence per 10 million mOPV2 doses administered; for nOPV2, this rate is approximately ten times lower at one emergence per 100 million doses.
nOPV2 Polio Vaccine Development
The nOPV2 vaccine's development began in 2011 through a consortium of experts led by the Bill & Melinda Gates Foundation, the U.K. National Institute for Biological Standards and Controls (NIBSC), the U.S. Centers for Disease Control and Prevention (CDC), PATH.org, and the University of California at San Francisco as an essential new tool in the fight against vaccine-derived poliovirus type 2 (cVDPV2). Since 2015, PATH has served as the convener of the nOPV2 product development consortium. On June 4, 2019, The Lancet published the findings of the initial phase 1 clinical trial conducted in 2017 at the University of Antwerp, which found nOPV2 safe and efficacious. In April 2022, the WHO's Strategic Advisory Group of Experts on Immunization (SAGE) noted the safety and genetic stability data on nOPV2, confirming the genetic stability of the vaccine and the non-inferior immunogenicity compared with monovalent oral polio vaccine type 2 (mOPV2). And nOPV2 is comparable with mOPV2 in terms of viral fecal shedding parameters. On March 28, 2023, the SAGE recommended that it be the preferred polio vaccine for response to cVDPV2 outbreaks wherever possible. In December 2023, the WHO issued nOPV2 prequalification approval under its EUL regulatory pathway. nOPV2 is the first vaccine to be WHO-prequalified after EUL.
nOPV2 Polio Vaccine For Children
A phase 3 clinical trial funded by the Bill & Melinda Gates Foundation concluded in February 2024 that the nOPV2 polio vaccine was immunogenic and safe in infants and young children in The Gambia. The data support the licensure and WHO prequalification of nOPV2.
nOPV2 Polio Vaccine Effectiveness
The Lancet Infectious Disease published results from an observational cohort study on January 15, 2024, that included 5,635 eligible children, of which 97.7% received at least one dose of nOPV2. Poliovirus type 2 seroconversion rates were 70% (95% CI 62 to 78; 87 of 124 children) following one dose of nOPV2 and 91% (85 to 95; 113 of 124 children) following two doses. Poliovirus excretion on day 7 was lower after the second round (162 of 459 samples; 35·3%, 95% CI 31·1 to 39·8) than after the first round (292 of 658 samples; 44·4%, 40·6 to 48·2) of the campaign (difference –9·1%; 95% CI –14·8 to –3·3), showing the induction of mucosal immunity. There was no axillary te to perature increase or baseline symptoms following either round of the campaigns. There were no adverse events of special interest or other safety signals of concern.
In January 2024, The Lancet Infectious Disease published a Comment by Martin Faye and Maria Dolores Fernandez-Garcia, concluding that continued research is necessary to understand the nOPV2 vaccine's real-world impact. This includes more field investigations and the long-term characterization of the genetic stability of nOPV2 through the sequencing of viral isolates. The Clinical Development and Evidence Summary was updated in April 2023.
nOPV2 Polio Vaccine Breakthrough Cases
According to the CDC's Morbidity and Mortality Weekly Report, from August 2021–July 2023, seven cVDPV2 emergences of nOPV2 origin from 61 paralytic cases and 39 environmental surveillance (sewage) samples were detected in six African countries. The isolates have limited divergence from the parental nOPV2 vaccine strain in the VP1 capsid protein-coding area (six to 16 nucleotide substitutions), indicating that surveillance detected emergence relatively early after vaccination.
The GPEI received notification on March 16, 2023, of the detection of cVDPV2 in seven children with acute flaccid paralysis (AFP) in Burundi and the Democratic Republic of the Congo (DRC) linked with the nOPV2 vaccine. The WHO reported on May 12, 2023, that nOPV2 retains its enhanced genetic stability compared to Sabin OPV2. Only 2% of all isolates reported so far have shown evidence of losing essential genetic modifications that reduce neurovirulence due to recombination, and these have only been detected in Africa versus the expected 75% for Sabin OPV2.
nOPV2 Polio Vaccine Indication
The WHO SAGE recommends offering nOPV2 and IPV vaccines during polio outbreaks. A research study published in npj Vaccines on February 11, 2022, confirms that nOPV2 is more stable against virulent mutations than licensed OPV2. This study directly assesses whether shedding nOPV2 virus against shed OPV2 virus in comparable groups. Furthermore, it shows that the attenuated nOPV2 vaccine is more resistant to reversion than OPV2. Therefore, on December 9, 2021, the WHO recommended that all travelers to polio-affected areas be fully vaccinated against polio. In addition, residents (and visitors for more than four weeks) from infected areas should receive an additional dose of oral polio vaccine or inactivated polio vaccine within 1 to 12 months of travel. On March 30, 2022, the GPEI released an updated version of the Standard Operating Procedures to guide any country's management that detects poliovirus outbreaks.
nOPV2 Vaccine Side Effects
A review of safety data on the first 65 million doses of nOPV2 used for outbreak response by the independent Global Advisory Committee on Vaccine Safety concluded that there were no apparent safety concerns. In April 2024, the U.S. CDC published - Novel Oral Poliovirus Vaccine 2 Safety Evaluation during Nationwide Supplemental Immunization Activity, Uganda, 2022, which concluded no safety signals were identified using a multipronged approach of passive and active surveillance.
nOPV2 Vaccine Virus Shedding
The Journal of Infectious Diseases, Volume 226, Issue 5, September 1, 2022, published results from clinical studies that found poliovirus shedding data were available from 621 initially reverse-transcription PCR–negative infants. Seven days after dose 1, 64.3% of mOPV2 recipients and 31.3%–48.5% of nOPV2 recipients across groups shed infectious type 2 virus. Respective rates seven days after dose 2 decreased to 33.3% and 12.9%–22.7%, showing induction of intestinal immunity. Shedding of both nOPV2 candidates ceased at similar or faster rates than mOPV2, and all vaccines showed indications that the vaccine virus was replicating sufficiently to induce primary intestinal mucosal immunity.
nOPV2 Vaccine Dosing
A paper published by Mejia and colleagues in 2023 provides promising findings in favor of a shorter nOPV2 vaccination schedule specifically for polio outbreak responses.
nOPV2 Polio Vaccine News
March 23, 2024 - A scientific paper reviewed the nOPV2 development through rollout and WHO prequalification, and it is being applied to combat global health emergencies.
February 9, 2024 - PLOS One published: One billion doses and WHO prequalification of nOPV2: Implications for the global polio situation and beyond
January 9, 2024—John Konz, Ph.D., nOPV project director and global head of Polio at PATH, stated in a press release, "I would like to commend the Bio Farma team for their dedication to parallel efforts to meet demand under the EUL while completing critical activities needed to achieve full licensure and WHO prequalification."
September 22, 2023 - The U.S. CDC published Notes from Vaccine-Derived Poliovirus Type 2 Emergences Linked to Novel Oral Poliovirus Vaccine Type 2 Use — Six African Countries, 2021–2023
May 12, 2023—The WHO committee noted that in the African Region, which uses nOPV2, two new cVDPV2 patients were detected in DRC, emerging from novel OPV2 use.
May 10, 2023 - The Lancet published: Immunogenicity of novel oral poliovirus vaccine type 2 administered concomitantly with bivalent oral poliovirus vaccine: an open-label, non-inferiority, randomized, controlled trial. Conclusion: Co-administration of nOPV2 and bOPV interfered with immunogenicity for poliovirus type 2 but not for types 1 and 3.
November 25, 2022 - The WHO released nOPV2 vaccines for use by Indonesia for approximately 95,000 children.
October 16, 2022 - The Gates Foundation announced it would commit $1.2 billion to support polio vaccinations.
October 11, 2022 - Since the 68th session of the Regional Committee, vaccination campaigns have resumed in Afghanistan, and the Region has implemented outbreak response campaigns using the nOPV2 vaccine.
September 23, 2022 - The Lancet published: A novel tool to eradicate an ancient scourge: the novel oral polio vaccine type 2 story. Monitoring the use of nOPV2 has confirmed it is more genetically stable and less likely to result in VDPV than the Sabin strain, suggesting that the target of the global eradication of poliomyelitis might be a little more attainable than previously believed.
June 17, 2022 - The U.S. CDC published Genetic Characterization of Novel Oral Polio Vaccine Type 2 Viruses During Initial Use Phase Under Emergency Use Listing — Worldwide, March–October 2021. nOPV2 is used to respond to poliovirus outbreaks with a comparatively low risk of generating new circulating strains.
April 28, 2022 - The polio outbreak in Tajikistan marked the first detection of cVDPV2 in the WHO European Region and is the first cVDPV2 outbreak in the world to be declared officially closed following supplemental immunization using the nOPV2 vaccine.
April 7, 2022 - The WHO's Strategic Advisory Group of Experts on immunization is convening in Geneva and will review updated data on novel oral polio vaccine type 2 (nOPV2) use and recommendations on initial planning for OPV cessation. The SAGE noted that a framework for a comprehensive analysis of nOPV2 performance is under development and requested periodic updates on the safety and genetic stability data of nOPV2.
February 11, 2022 - The journal NPJ Vaccines published a study that concluded: The available data from a key target age group for outbreak response confirm the superior genetic and phenotypic stability of shed nOPV2 strains compared to shed Sabin-2 and suggest that nOPV2 should be associated with less paralytic disease and potentially lower risk of seeding new outbreaks.
October 11, 2021 - Following a careful review of the safety and genetic stability data from mass immunization campaigns conducted with the novel oral polio vaccine type 2 (nOPV2), the Strategic Advisory Group of Experts on immunization (SAGE) today endorsed the transition to the following use phase for the vaccine.
March 13, 2021 - nOPV2 will be rolled out in Africa to fight vaccine-derived poliovirus type 2 outbreaks. Poor polio strains occur in under-immunized communities with limited access to safe water and sanitation.
July 29, 2021 - The journal Nature published the results of a study - Because of the safety, immunogenicity, and promising phenotypic stability of these viruses, nOPV2 use under Emergency Use Listing (EUL) features prominently in the Global Polio Eradication Initiatives' new strategy to stop further spread of cVDPV21. The EUL has recently been granted for nOPV2-c1. The methods described here are now being applied to shed virus from paired phase 4 and phase 2 clinical trials of mOPV2 and nOPV2 in children and infants, allowing a more direct comparison of the molecular evolution and virulence of shed nOPV2 viruses with shed Sabin 2 in the age groups that will be the focus of outbreak responses.
nOPV2 Clinical Studies
nOPV2 polio vaccine has been in several clinical studies and is in various stages. Clinical summaries for the nOPV2 vaccine.
