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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.Clinical Considerations for Children who Received
Fractional Dose Inactivated Polio Vaccine ( fIPV ) in
Other Countries
Sarah Kidd, MD, MPH
ACIP Meeting
February 28, 2024
▪Wild poliovirus type 2 eradicated in 2015
▪Global switch and withdrawal of Sabin type 2 virus from OPV in April 2016:
–Replaced all trivalent OPV ( tOPV ; types 1, 2, and 3) with bivalent OPV ( bOPV ; types 1 and 3)
–≥1 dose IPV recommended as part of routine immunization in all countries using bOPV
▪Based on clinical trial data and limited IPV availability, WHO supports use of 2
fractional doses of IPV (1/5 full dose IPV) given intradermally in place of single full
IPV dose (intramuscular)Background
WHO. World Epidemiological Record 2016;91:561 –82.
WHO. World Epidemiological Record 2021;96:613 –32.
https://www.who.int/teams/immunization -vaccines -and-biologicals/diseases/poliomyelitis -(polio)
ONE fractional IPV ( fIPV ) dose is LESS immunogenic than
one full IPV dose
Meta -analysis of percent that seroconverted for poliovirus type 2 ( Mashunye 2021)
Mashunye et al. Lancet Infect Dis 2021;21:1161 –74.
TWO fractional IPV ( fIPV ) doses are MORE immunogenic
than one full IPV dose
Slide adapted from Concepcion Estivariz.
Data from Snider et al. Lancet 2019; 393:2624. 0102030405060708090
Type 1 Type 2 Type 3Percent with seroconversion at 18 weeks
2 fIPV 6 & 14 wk 1 IPV 6 wk 1 IPV 14 wk
* P< 0.01 versus 2 fIPV doses **
**
* *
▪6 countries (~20% of global birth cohort) use 2 fIPV doses + ≥3 bOPV doses in routine
childhood immunization schedule
–Bangladesh, Cuba, Ecuador, India, Nepal, Sri Lanka
Example polio vaccination schedule (India):Current Use of fIPV in Routine Immunization Globally
Birth 6 weeks 10 weeks 14 weeks 16–24
monthsTotal doses
bOPV X X X X X 5 bOPV
fIPV X X 2 fIPV
▪Recommended polio vaccination
–4 total IPV doses, administered at 2, 4, 6 –18 months, and 4 –6 years OR
–3 total IPV doses if 3rd dose administered after 4th birthday and ≥6 months after 2nd dose
▪For vaccines administered outside of US
–Only tOPV or IPV doses considered valid for US vaccination schedule
Example polio vaccination schedule (India):Current US Guidance
Birth 6 weeks 10 weeks 14 weeks 16–24
monthsTotal
doses
bOPV X X X X X 5 bOPV
fIPV X X 2 fIPVCurrent US guidance:
•None of these
doses considered
valid in US
•Needs 3 –4 full IPV
doses in US
Should 2 fractional IPV doses administered outside of the United States
be counted as either 1 or 2 doses towards the US vaccination schedule?Question for Work Group:
▪Previous meta -analysis published in 2021 ( Mashunye et al)
▪Literature review using same search terms; searched Medline, Embase, Cochrane
Library, Scopus, and ClinicalTrials.gov
–Randomized clinical trials
–Compared 2 fIPV doses to either 1 or 2 IPV doses
–Published between January 1, 2019 and June 30, 2023
▪Outcomes
–Seroconversion for poliovirus type 2
•Change from seronegative (titer <1:8) to seropositive (titer ≥1:8) OR
•≥4-fold increase in antibody titer over expected decline in maternal antibodies
–Changes in geometric mean titersMethods: Updated Meta -Analysis
Mashunye et al. Lancet Infect Dis 2021;21:1161 –74.
Seroconversion: 2 fIPV Doses vs. 1 IPV Dose
Seroconversion: 2 fIPV Doses vs. 2 IPV Doses
Seroconversion: 2 fIPV doses are less favorable vs. 2 IPV
doses when given at younger age
6 and 14 weeks
2 and 4 months
10 and 14 weeks
4 and 8 months
14 weeks and 36 weeks
3 and 11 –15 months14 weeks and 9 months4 and 8 months6 and 10 weeksAge
Median Antibody Titers Lower After 2 fIPV vs. 2 IPV Doses
Resik 2010 (3 doses at 6, 10, and 14 weeks)
Mohammed 2010 (3 doses at 2, 4, and 6 months)
Resik 2020 (2 doses at 4 and 8 months)
fIPVIPVfIPVIPV
Age fIPV IPV
Resik 2013 4 and 8 months 898 (713 -≥1448) ≥1448 (≥1448 -≥1448)
Aziz 2022 9-13 and 11 -15 months 455 (362 -724) ≥1448 (1152 -≥1448)Resik 2013 and Aziz 2022: Median titer (95% CI) after 2 doses
Resik et al, J Infect Dis 2010; Resik et al, J Infect Dis 2020; Mohammed et al, N Engl J Med 2010; Resik et al, N Engl J Med 201; Aziz et al, J Infect Dis 2022.
Geometric Mean Titers: 2 fIPV vs. 2 IPV Doses
Bandyopadhyay et al. Lancet Infect Dis 2021;21:559 –68.
(10-14-36 weeks)
(14-36 weeks)
(10-14-36 weeks)
(14-36 weeks)4 weeks after 2 doses
IPV vs. 2 doses fIPV
(given at 10 and 14
weeks)4 weeks after 2 doses
IPV vs. 2 doses fIPV
(given at 14 and 36
weeks)
Persistence of Poliovirus Type 2 Antibodies Following 2 fIPV
or 2 IPV Doses
Saleem et al. JID 2021; 223(7)1214
Slide adapted from Concepcion Estivariz.
•As immunization
series with fIPV
reach lower final
titers, seronegativity
expected to be
reached earlier 2 IPV doses
2 fIPV doses
▪WHO supports the use of 2 fIPV doses in place of 1 IPV dose as an IPV conservation
strategy
▪2 fIPV doses associated with higher rates of seroconversion vs. 1 IPV dose
▪2 fIPV doses associated with slightly lower rates of seroconversion vs. 2 IPV doses
–Especially when administered at 6 and 14 weeks; rates of seroconversion approach equivalency at older ages
of administration
▪Peak antibody titers are lower after 2 fIPV doses vs. 2 IPV dosesSummary
▪For persons who received fractional (1/5 full dose) IPV administered intradermally
outside of the United States, 2 fractional doses of IPV ( fIPV) should be considered
valid and counted as 1 full intramuscular dose of IPV towards the US vaccination
schedule.
▪If a person received only 1 dose of fIPV, this dose should not be considered valid or
counted towards the US vaccination schedule.Proposed CDC Clinical Considerations
Questions and Discussion
▪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