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Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.Considerations for the Potential Use of Novel Type 2 Oral
Poliovirus Vaccine (nOPV2) as an Outbreak Control
Measure in the United States
Sarah Kidd, MD, MPH
ACIP Meeting
February 28, 2024
▪ACIP voting members
–Oliver Brooks (Chair)
–Lynn Bahta
–Sybil Cineas
▪Liaisons
–Lynn Fisher, American Academy of Family Physicians
–Chandy C. John, American Academy of Pediatrics
–Sandra Fryhofer , American Medical Association
–Kathy Kudish, Association of Immunization Managers
–Marcus Plescia , Association of State and Territorial Health Officials
–Paul R. Cieslak , Council of State and Territorial Epidemiologists
–Christine Hahn, Council of State and Territorial Epidemiologists
–Tina Q. Tan, Infectious Diseases Society of America
–Adenike Shoyinka , Infectious Diseases Society of America
–Mary Wilson, International Society of Travel Medicine
–Jaqueline Lawler, National Association of County and City Health Officials
–Kathy Edwards, Pediatric Infectious Diseases Society
–Joseline Zafack , Public Health Agency of Canada*Polio Work Group Members
*In the event of a Work Group poll, CDC, FDA, and Public Health Agency of Canada members are not included.▪Consultants
–Edwin Asturias
–Doug E Campos -Outcalt *
–Emily Lutterloh
–Jennifer Rosen
–Eli Rosenberg
▪FDA*
–Robin Levis
▪CDC*
–Cara Burns
–Thomas Clark
–Miranda Delahoy
–Brian Edlin
–Concepcion Estivariz
–Halle Getachew
–Sarah Kidd
–Janelle King
–Adriana Lopez
–M. Steve Oberste
▪Poliovirus infection can cause
poliomyelitis and lifelong paralysis
–Paralytic disease occurs in <1% of
infections (varies by serotype)
–Non -paralytic clinical illness occurs in
~25%, including 1% –5% with aseptic
meningitis
–Approximately 75% of infections are
asymptomaticPublic Health Problem
▪Three poliovirus serotypes: type 1, type 2, and type 3
▪Immunity to one serotype does not result in significant
immunity to other serotypes
▪Ratio of paralytic cases to infections varies by serotype
–Type 1: approximately 1/190
–Type 2: approximately 1/1900
–Type 3: approximately 1/1100Poliovirus Serotypes
Nathanson N, Kew OM. Am J Epidemiol 2010;172:1213 –29.
▪Person -to-person spread of poliovirus occurs via the fecal -oral or oral-oral routes
–Fecal -oral is the most important transmission pathway in settings with suboptimal
hygiene and sanitation
▪Patients are most infectious during days immediately before and after onset of
symptoms, but virus may remain present in stool for up to 6 weeks , sometimes
longer
–Individuals with minor symptoms or no illness can shed virusPoliovirus is highly infectious
▪Only polio vaccine used in the US
▪Contains inactivated polioviruses types 1, 2, and 3 polioviruses
▪Induces effective humoral immunity → prevents paralysis
▪Induces some nasopharyngeal mucosal immunity, butlimited
intestinal immunityInactivated Polio Vaccine (IPV)
▪Live attenuated vaccine (Sabin)
–Trivalent OPV ( tOPV ): contains types 1, 2, and 3
–Bivalent OPV ( bOPV ): contains types 1 and 3
–Monovalent OPV ( mOPV #): contains single type (#=1, 2, or 3)
▪Replicates in gut, is shed in stool
▪Induces humoral and mucosal immunity
–Prevents paralysis and transmission ofpoliovirus
▪Historical vaccine of choice for countries with outbreaks
▪Attenuated virus can revert to a neurovirulent form
that causes paralysisOral Polio Vaccine (OPV)
▪Novel, next -generation version of monovalent type 2 oral polio vaccine (nOPV2)
▪Designed to be more genetically stable, less likely to revert to neurovirulent form
▪March 2021 –December 2023:
–Almost 1 billion doses administered in 35 countries under WHO Emergency Use
Listing (EUL) approval
▪December 2023: Earned WHO prequalificationNovel Type 2 Oral Polio Vaccine (nOPV2)
Paralytic polio decreased rapidly in the US after
introduction of polio vaccine
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20201994: Americas
certified polio -free
YearNumber of poliomyelitis cases1955: Salk IPV
1961: Sabin OPV1979: Last indigenous
wild-type case in US
2000: IPV only1997 : Sequential enhanced -potency
IPV followed by OPV
Global Paralytic WPV1 and cVDPV Cases1, Previous 12 Months2
https://polioeradication.org/polio -today/polio -now/
WPV1 cases (latest onset)
Pakistan 5 24-Oct-23
Afghanistan 6 04-Sep-23
cVDPV1 cases (latest onset)
DR Congo 90 24-Nov-23
Mozambique 3 06-Nov-23
Madagascar 17 16-Sep-23
cVDPV2 cases (latest onset)
Niger 2 11-Dec-23
Indonesia 3 06-Dec-23
Nigeria 80 03-Dec-23
Zimbabwe 1 02-Dec-23
Guinea 46 28-Nov-23
Chad 49 26-Nov-23
Côte d'Ivoire 6 22-Nov-23
DR Congo 87 19-Nov-23
Yemen 4 17-Nov-23
Tanzania 3 16-Nov-23
Mali 12 06-Nov-23
South Sudan 2 04-Nov-23
Mauritania 1 17-Oct-23
CAR 10 07-Oct-23
Mozambique 1 28-Sep-23
Somalia 4 16-Sep-23
Kenya 8 21-Aug-23
Burundi 1 15-Jun-23
Burkina Faso 2 04-Jun-23
Zambia 1 03-Apr-23
Benin 2 15-Mar-23Data in WHO HQ as of 20 Feb. 20241Excludes viruses detected from environmental surveillance; 2Onset of paralysis: 21 Feb. 2023 to 20 Feb. 2024Endemic country (WPV1)
Paralytic Polio Case in New York State, July 2022
•A case of paralytic polio caused by vaccine -derived poliovirus type 2 (VDPV2) was
confirmed in an unvaccinated young adult from Rockland County, New York, on
July 21, 2022
•Genetic sequencing has indicated a linkage to polioviruses collected in
wastewater in Israel, United Kingdom, and Canada
•Rockland County has reported overall low vaccine coverage for over 20 years
•In summer 2022, 60% of children under 2 years of age had received 3 doses of
IPV (zip code level as low as 37%)
•No additional paralytic cases were identified
https://www.health.ny.gov/diseases/communicable/polio/docs/waste_water_surveillance_report.pdf ▪Poliovirus type 2 genetically linked to the case detected
in wastewater samples in New York (Rockland, Orange,
Sullivan, and Nassau counties and New York City)
▪Retrospective testing detected poliovirus as early as
April 2022
▪Only 2 positive samples since November 1, 2022 (most
recent February 22, 2023)
▪No detections in samples collected in last 11+ months
(since February 2023)Wastewater Testing for Poliovirus in New York
https://www.health.ny.gov/diseases/communicable/polio/docs/waste_water_surveillance_report.pdf
▪2022 New York Strategy: Identify unvaccinated and undervaccinated persons, provide
catch -up vaccination with IPV
▪WHO recommendations for poliovirus outbreaks in countries with exclusive IPV
vaccination and high sanitation and hygiene:
–Conduct a timely outbreak response with IPV only if poliovirus transmission is
confined in a well -defined population group or geographic area.
–If transmission persists, consider an OPV response.
▪Work Group asked to discuss considerations for potential use of nOPV2 as an
outbreak response measure in the USOutbreak Response Vaccination
▪Should nOPV2 be used in combination with a catch -up IPV campaign during a
future type 2 poliovirus outbreak in the US?
–Population: Persons living in area with circulating poliovirus
–Intervention: nOPV2 vaccination for all + catch -up IPV vaccination for un - or under -vaccinated
–Comparison: Catch -up IPV vaccination only
–Outcomes:
•Prevention of paralytic poliomyelitis
•Extent and duration of poliovirus circulation in the community
•Serious adverse effects, including vaccine -associated paralytic polio
•Possible introduction of new vaccine -derived poliovirus type 2Theoretical Policy Question for Work Group
▪Problem
–Is the problem of public health importance?
▪Benefits & Harms
–How substantial are the desirable anticipated effects?
–How substantial are the undesirable anticipated effects?
–Do the desirable effects outweigh the undesirable effects?
–What is the overall certainty of this evidence for the critical outcomes?
▪Values
–Does the target population feel that the desirable effects are large relative to the undesirable effects?
–Is there important uncertainty about or variability in how much people value the main outcome?
▪Acceptability
–Is the intervention acceptable to key stakeholders?
▪Resource Use
–Is the intervention a reasonable and efficient allocation of resources?
▪Equity
–What would be the impact on health equity?
▪Feasibility
–Is the intervention feasible to implement?ACIP Evidence to Recommendations ( EtR) Framework
Work group interpretation
Is paralytic poliomyelitis a problem of public health importance?EtR Domain: Public Health Problem
NoProbably
noProbably
yesYes VariesDon’t
know
▪Seroconversion among infants who had received 1 dose of IPV (Sáez -Llorens et al)
–86% 28 days after 1 dose
–98% 28 days after 2 doses
▪Seroconversion among vaccine -naïve infants (Zaman et al; Wilkinson et al)
–46% –64% 28 days after 1 dose
–86% –90% 28 days after 2 dosesEffectiveness:
High Rates of Seroconversion Following nOPV2
Sáez -Llorens et al. Lancet 2021;397:27 –38.
Zaman et al. Lancet 2023;401:131 –39.
Wilkinson et al. Lancet Infect Dis 2023;23:1062 –71.
▪Sabin OPV2 reduces odds of fecal shedding of type 2 virus after a challenge ( Hird and
Grassly )
▪In small Phase 1 study among adults previously vaccinated with IPV ( Brickley et al)
•33% had detectable stool neutralization titer against PV2 at 28 days after 1 dose of nOPV2
•15% had detectable PV2 -specific IgA in stool at 28 days after 1 dose of nOPV2Effectiveness: Mucosal Immunity
Hird and Grassly . PLoS Pathogens 2012;8(4):e1002599.
Brickley et al. J Infect Dis 2022;26:287 –91.
Fecal Shedding of nOPV2 Virus After 1st Dose of nOPV2
% of Infants* with Detectable nOPV2 Virus in Stool
Days after 1st dose of nOPV2 Measured by PCR Measured by Culture
7 days 85% 40%
14 days 52% 17%
28 days 40% - 57% 1% - 14%
Zaman et al. Lancet 2023;401:131 –39.
Gast et al. J Infect Dis 2022;226:852 –61.*Includes newborn vaccine -naïve infants and infants who had previously received 3 bOPV doses and 1 IPV dose
▪nOPV2 more genetically stable than Sabin OPV2, less likely to regain neurovirulence
▪Risk of VAPP in recipients
–nOPV2: estimated 0.07 cases per million recipients (1 per 14.3M recipients)
–Sabin OPV: 0.25 –4 cases per million recipients (1 per 0.25M –4M recipients)
–Risk highest in unimmunized children receiving 1st dose of OPV or in
immunocompromised persons
–Could be mitigated by limiting nOPV2 administration to persons who had
previously received ≥1 IPV doseRisk of Vaccine -Associated Paralytic Polio (VAPP) Following
nOPV2
Bandyopadhyay and Zipursky. Lancet ID 2023;23:e67 –71.
▪>700 million nOPV2 doses administered worldwide in 32 countries since March 2021
–At least 7 separate emergences of new cVDPV2 linked to nOPV2 (cVPDV2 -n)
–At least 61 detected paralytic cases associated with cVDPV2 -n
▪Estimates: nOPV2 is 80% less likely than mOPV2 to seed new cVDPV2
▪Risk of new cVDPV is highest when campaign coverage is low in a population with
low immunity against poliovirusesRisk of Introducing a New Circulating Vaccine -Derived
Poliovirus ( cVDPV ) Following nOPV2
Davlantes et al. MMWR 2023;72(38):1041 –1042.
https://polioeradication.org/wp -content/uploads/2024/01/GPEI -nOPV2 -Factsheet -20240105.pdf
▪Most recipients will already be fully vaccinated with 3 –4 doses of IPV, already
protected against paralytic disease
▪Anticipated benefits of nOPV2 to recipient
–Higher anti -poliovirus type 2 antibody titer
–Increased odds of mucosal immunity to poliovirus type 2
–For undervaccinated persons: additional protection against paralytic disease
–For previously vaccinated persons: unlikely clinical benefit
▪Potential harms of nOPV2 to recipient
–Extremely low, but non -zero risk of VAPP (<1 case per 14.3 million doses administered)
–Risk of chronic infection if given to child with unrecognized immunocompromiseFor Individual nOPV2 Recipients
Potential effects of adding nOPV2 to the IPV outbreak response
▪Potential benefits to population
–Decreased transmission among nOPV2 recipients → outbreak ends earlier → fewer paralytic cases
–Passive vaccination of unvaccinated → decreased transmission and fewer paralytic cases
▪Potential harms to population
–Passive vaccination of unvaccinated → risk of VAPP among unvaccinated
–Possible ongoing transmission of nOPV2 virus → new cVDPV2 -n
–Possible chronic infection in immunocompromised
▪Magnitude of benefits and harms depends on nOPV2 coverage, extent of mixing
between nOPV2 recipients and unvaccinated (and immunocompromised)At the Population Level
Potential effects of adding nOPV2 to the IPV outbreak response
Modeling:
Expected Paralytic Cases Under Different Mixing Scenarios
for a cVDPV2 Outbreak Similar to 2022 New York Outbreak
Thompson et al. Vaccine 2024;42:819 –27.
Note: Model assumed the number of vaccine doses administered was same as number of IPV doses administered
during 2022 New York outbreak.Modeled cVDPV2 cases
Vaccine used for outbreak response IPV None mOPV2 nOPV2 best nOPV2 worst
Subpopulation isolation 0.88 1.89 0.64 0.55 0.67
No isolation 0.64 0.86 0.51 0.44 0.53
Partial isolation 0.35 0.39 0.30 0.27 0.31
Modeling:
Expected Paralytic Cases Under Different Mixing Scenarios
for cVDPV1 Outbreak and Hypothetical Novel Type 1 OPV
Thompson et al. Vaccine 2024;42:819 –27.
Modeled cVDPV1 cases
Vaccine used for outbreak response IPV None mOPV1 nOPV1 best nOPV1 worst
Subpopulation isolation 56 65 45 22 47
No isolation 130 179 91 26 97
Partial isolation 36 163 23 11 25
Note: Model assumed the number of vaccine doses administered was same as number of IPV doses administered
during 2022 New York outbreak.
Minimal Small Moderate Large VariesDon’t
knowEtR Domain: Benefits & Harms
Work group interpretation
How substantial are the desirable anticipated effects of nOPV2* on the
individual and population levels?
*during a VDPV2 outbreak, when nOPV2 given in addition to any IPV doses received as part of routine immunization
Minimal Small Moderate Large VariesDon’t
knowEtR Domain: Benefits & Harms
Work group interpretation
How substantial are the undesirable anticipated effects of nOPV2* on
the individual and population levels?
*during a VDPV2 outbreak, when nOPV2 given in addition to any IPV doses received as part of routine immunization
Yes, favors
nOPV2No, favors IPV
onlyFavors either
option equallyVaries Don’t knowEtR Domain: Benefits & Harms
Work group interpretation
Do the desirable effects of nOPV2* outweigh the undesirable effects on
the individual and population levels?
*during a VDPV2 outbreak, when nOPV2 given in addition to any IPV doses received as part of routine immunization
▪Expanded access investigational new drug application (EA -IND)
▪Requires application to FDA and FDA authorization
▪If implemented, nOPV2 EA -IND program must include
–Signed informed consent by vaccinees and/or guardians
–System for monitoring vaccine safety
–Enhanced surveillance for possible VAPP cases
–Environmental surveillance for new cVDPV2s
–System for tracking and accounting for every dose for containment purposesImplementing an nOPV2 Program in the US
NoProbably
noProbably
yesYes VariesDon’t
knowEtR Domain: Resource Use
Work group interpretation
Is an nOPV2 campaign* a reasonable and efficient allocation of
resources?
*during a VDPV2 outbreak, when nOPV2 given in addition to any IPV doses received as part of routine immunization
NoProbably
noProbably
yesYes VariesDon’t
knowEtR Domain: Feasibility
Work group interpretation
Is a nOPV2 campaign* feasible to implement?
*during a VDPV2 outbreak, when nOPV2 given in addition to any IPV doses received as part of routine immunization
▪Trivalent OPV ( tOPV ) was removed from vaccination schedule in 2000 and replaced with IPV because
any risk of VAPP was deemed unacceptable; this might be barrier to acceptance of a new OPV vaccine
▪The need for signed informed consent will likely be a deterrent
▪Unclear whether general public will accept an OPV if they are already protected from paralytic
infection by IPV
▪Unclear whether population most at risk (those with low childhood vaccination coverage and high
rates of vaccine skepticism) will accept an OPV vaccine
▪Perceptions of risk and vaccine acceptance might shift in outbreak setting, if there is >1 paralytic case
in a communityValues and Acceptability Considerations
NoProbably
noProbably
yesYes VariesDon’t
knowEtR Domain: Values of Target Population
Work group interpretation
Does the target population feel that the desirable effects of nOPV2* are
large relative to undesirable effects?
*during a VDPV2 outbreak, when nOPV2 given in addition to any IPV doses received as part of routine immunization
Important
uncertainty
or variabilityProbably
important
uncertainty
or variabilityProbably not
important
uncertainty
or variabilityNo
important
uncertainty
or variabilityNo known
undesirable
outcomesEtR Domain: Values of Target Population
Work group interpretation
Is there important uncertainty or variability in how much people value
the main outcomes?
NoProbably
noProbably
yesYes VariesDon’t
knowEtR Domain: Acceptability to Key Stakeholders
Work group interpretation
Is nOPV2* acceptable to key stakeholders?
*during a VDPV2 outbreak, when nOPV2 given in addition to any IPV doses received as part of routine immunization
Globally
▪Single manufacturer ( BioFarma , Indonesia)
▪Managed via a global stockpile
▪Supply shortages have occurred in the past
▪In US, IPV is readily available, provides protection against paralysis from cVDPV2
▪In many countries with cVDPV2 outbreaks, limited protection against cVDPV2 unless
there are nOPV2 or mOPV2 campaigns
In US
▪Preventing transmission protects unvaccinated/undervaccinated and
immunocompromisedEquity Considerations
Reduced
equityProbably
reduced
equityProbably
no impactProbably
increased
equityIncreased
equityVariesDon’t
knowEtR Domain: Equity
Work group interpretation
What would be the impact of an nOPV2 campaign* in the US on health
equity?
*during a VDPV2 outbreak, when nOPV2 given in addition to any IPV doses received as part of routine immunization
Undesirable
consequences
clearly
outweigh
desirable
consequences
in most settingsUndesirable
consequences
probably
outweigh
desirable
consequences
in most
settingsThe balance
between
desirable and
undesirable
consequences
is closely
balanced or
uncertainDesirable
consequences
probably
outweigh
undesirable
consequences
in most settingsDesirable
consequences
clearly
outweigh
undesirable
consequences
in most settingsThere is
insufficient
evidence to
determine the
balance of
consequencesWork Group Judgement: Balance of Consequences
Using nOPV2 as an outbreak control measure in the US*
*during a VDPV2 outbreak, when nOPV2 given in addition to any IPV doses received as part of routine immunization
▪At this time, the work group believes the undesirable consequences probably
outweigh OR are closely balanced with the desirable consequences.
▪Main considerations included
–IPV is readily available in the US and protects against paralytic disease
–Primary benefit of adding nOPV2 to an outbreak response would be to reduce transmission of outbreak virus,
reduce risk of paralytic disease in undervaccinated or immunocompromised persons
–Differences of opinion regarding the value of reducing asymptomatic transmission or ending asymptomatic
transmission earlier during outbreak
–Extremely low, but non -zero risk of VAPP (est. 1 per 14.3 million recipients) or new cVDPV2
–Uncertainty about public and stakeholder acceptance of nOPV2
▪Balance of undesirable consequences vs. desirable consequences might shift in the
future depending on size and scope of outbreakSummary
Use of nOPV2 During a cVDPV2 Outbreak in the US
Questions and Discussion