ipv use & challenges · source: gvmm, ipv supply update, 2016, bmgf analysis, october 2016...

© 2015 Bill & Melinda Gates Foundation

IPV USE & CHALLENGES

October 26, 2016

Child receiving IPV with tOPV during NID in Kano City, March 2015

Shanda Boyle, MSc, MPH

Bill and Melinda Gates Foundation

Polio program, Global Development

RATIONALE FOR OPV CESSATION

© Bill & Melinda Gates Foundation | 2

3

DRAMATIC PROGRESS:

ANNUAL GLOBAL POLIO CASE BURDEN

Source: WHO/Polio database

0

100

200

300

400

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

*

2010

2011

2012

2013

2014

2015

Num

ber (

thou

sand

s)

Americas certified

polio free

Last case in China

Last cases in Pacific &

Euro regions

Last case of Type 2

mOPV vaccine

bOPV vaccine

WHA Resolution

to eradicate polio

99% REDUCTION in number

of cases

Last case of Type 3 74 cases

globally

India certified

polio-free

© Bill & Melinda Gates Foundation |

4

NUMBER OF CASES RELATED TO VACCINE-DERIVED POLIOVIRUSES IN COMPARISON TO WILD POLIOVIRUS

Patel, et al. Expert Rev. Vaccines 2015 .1.online

Since 1999, indigenous transmission of type 2 wild poliovirus has not

been detected

The type 2 component of tOPV:

• Causes more than 90% of vaccine-derived polio viruses (VDPVs)

• Causes approx. 40% of vaccine-associated paralytic polio (VAPP) cases

• Interferes with immune response to types 1 and types 3

IPV introduction will help to boost immunity to all three types, prior to

the switch

RATIONALE FOR SWITCHING FROM TRIVALENT OPV TO BIVALENT OPV

Currently, the risk associated with the type 2

component of tOPV outweigh the benefits

Global Polio Eradication


Oral poliovirus vaccine (OPV) • Utilized to achieve eradication

• Generally safe

• Low Cost

• Easy delivery

• Reduction of efficacy

• In rare cases OPV has been

associated with vaccine-

associated polio (VAPP) and

circulating vaccine-derived

polioviruses (cVDPVs)

OPV AND IPV HAVE THEIR OWN ADVANTAGES AND CHALLENGES

Inactivated poliovirus vaccine (IPV)

• Safe (inactivated virus: non-

infectious and genetic stable)

• Efficacious vaccine

• Has been sufficient to “maintain”

eradication in regions with good

sanitation and high vaccine coverage

• Intestinal immunity modest in

comparison with OPV

• Protects individual but WT virus shed

• Less easy to deliver

• Expensive in comparison to OPV

VACCINE CHOICE IN THE ERADICATION ENDGAME

2013 2014 2017 2018 2020 2019 2016 2015 2012

tOPV-

bOPV

switch

Use of IPV, bOPV & tOPV

Last use

of bOPV

Global

Certification

Last wild

polio

case

bOPV + 1 dose IPV in routine

immunization ≥ 1 IPV doses

Introduce 1

dose IPV in RI

“complete the eradication and containment of all wild, vaccine-related, and Sabin polioviruses such that no child ever again suffers paralytic poliomyelitis.”

LATEST GPEI

STRATEGIC PLAN

OBJECTIVE


Current WHO IPV Recommendation

• For IPV only -using countries: 3 doses of IPV

• For OPV-using countries: at least 1 dose of IPV at 14 weeks

CURRENT IPV USE – ROUTINE IMMUNIZATION AND CAMPAIGN


POLIO ERADICATION STRATEGY

Routine Immunization

National Immunization Days (NIDs)

• Vaccinating all children <5 years of

age regardless of vaccination status

‒ Also known as Mass Campaigns or

Supplemental Immunization Activities

(SIAs)

Careful surveillance

Mop-up campaigns

From “Introduction to Poliomyelitis”. Training of STOP Team 34, Atlanta, May 2010

Global Polio Eradication Initiative

9 © Bill & Melinda Gates Foundation |

COUNTRIES USING IPV VACCINE TO DATE AND FORMAL DECISION TO INTRODUCE

Data source: WHO/IVB Database, as of 03 May 2016

Map production Immunization Vaccines and Biologicals (IVB),

World Health Organization

Date of slide: 3 May 2016

The boundaries and names shown and the designations used on this map do not imply the

expression of any opinion whatsoever on the part of the World Health Organization

concerning the legal status of any country, territory, city or area or of its authorities, or

concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent

approximate border lines for which there may not yet be full agreement. ©WHO 2016.

All rights reserved.

Introduced to date* (168 countries or 87%)

(20 countries or 10%)

Not available

Not applicable

Introduction delayed in 2017

Formal commitment to introduce in 2016 (6 countries or 3%)

* Including partial introduction in India

• 100/126 countries have introduced since 2013

• 6 more countries plan to introduce in 2016

• 20 countries will introduce in 2017 due to IPV supply shortages


Good immunogenicity with ≥ 2 doses of bOPV for type 1 and type 3 polioviruses

High rates of seroconversion to type 2 poliovirus have been seen

- with one dose of IPV at 14 weeks

- with two doses of IPV (seroconversion is near 100% depending on the age of

administration)

Evidence of a high rate of immune priming for type 2 antibody following one dose of

IPV

© Bill & Melinda Gates Foundation |

bOPV AND IPV IN EPI (6-10-14 WEEK) SCHEDULE

ROLE OF FRACTIONAL DOSE IPV


© Bill & Melinda Gates Foundation | 13 © Bill & Melinda Gates Foundation | 13

FRACTIONAL DOSING OF IPV

Due to IPV supply shortage, 40+ countries are not able to use IPV.

WHO has recommended, and SAGE recently endorsed, that countries consider

fractional dosing of IPV (fIPV) delivered intradermally (ID). • Recommendation is based on clinical data in comparison to 1 IM dose of IPV.

• Routine immunization: Two doses fIPV delivered ID at six and 14 weeks, along with bOPV.

• Campaign immunization: One dose fIPV delivered ID to be given along with mOPV or bOPV.

Routine immunization:

• fIPV is currently being implemented in all states in India.

• Under consideration for introduction in additional countries including Sri Lanka and possibly

Bangladesh.

Campaign immunization:

• fIPV campaign completed in Hyderabad, India area in July 2016 in response to VDPV2 detection

in sewage (~300,000 children).

Outstanding country uptake and operational questions remain

Adapted from a slide by PATH

IPV SUPPLY – CURRENT AND PROJECTED


Date of slide: 1 June 2015 15

• Challenges due to problems with scale-up and manufacturing

processes

• About 40% less IPV available than what was awarded through the

initial UNICEF tender in 2014

• Severely reduced supply available: approximately 45 Tier 3 and

Tier 4 countries negatively affected

• The IPV supply constraints are expected to remain dynamic until

at least 2018 and will continue to be closely monitored by UNICEF

and WHO

IPV SUPPLY CONSTRAINTS: BACKGROUND

Adapted from GPEI

M

50M

100M

150M

200M

250M

300M

350M

400M

450M

500M

2016 2017 2018 2019 2020 2021 2022 2023 2024

Low

Medium

High

PQ andApprovedChina

Two DoseDemand

One DoseDemand

ESTIMATED IPV DEMAND AND SUPPLY

Notes: Demand represents all 124 IPV introduced or introducing countries, including China and India; public market

and RI only (not outbreak or catch-up demand). Factors in wastage by presentation. Demand does not account for

fIPV usage, assumes a full dose vaccine

Source: GVMM, IPV supply update, 2016, BMGF analysis, October 2016

Under realistic supply assumptions, some countries may be able to introduce a 2nd dose of IPV in 2020, but there is

greater likelihood to meet total global demand for a 2-dose schedule from 2021.

Global Certification

Doses/y

ear

16

Demand

Significant demand uncertainty still exists

around future IPV dosage recommendations

and duration of use post-certification

A SAGE 2-dose recommendation would likely

require at least 80M additional IPV doses to

meet demand from 2020.

Some countries included in the forecast may

choose to use combination vaccines and move

to a 3-dose schedule

Supply

The 2020+ IPV market will likely be competitive

Supply includes standalone IPV only (not

combination vaccines or fractional intradermal).

High, Medium, and Low refers to confidence in

that supply capacity being NRA approved or

PQed, available, and affordable for public

markets.

Date of slide: 1 June 2015

17

The Polio Oversight Board, which is made up of the heads of agencies

of GPEI partners agreed to the following:

1. Ensure adequate IPV supply to meet current and future needs of

Afghanistan, Pakistan to ensure interruption of WPV transmission

2. Sustain use of IPV in routine immunization programme in highest risk

(tier 1 and Tier 2) countries

3. Ensure sufficient quantities are available for outbreak response post-

Switch.

4. Provide clarity to tier 3 and 4 countries regarding supply availability

so they can plan, avoiding ad-hoc delays

MANAGING THE CONSTRAINED IPV SUPPLY

Adapted from GPEI

© 2015 Bill & Melinda Gates Foundation | 18

BMGF SUPPLY PRIORITIES

A reliable supply of significant quantities of affordable OPV is essential to achieving polio eradication

bOPV and mOPV have roles in SIAs including use as outbreak control and vaccine stockpiling

1. Ensure

Reliable

Supply of

OPV

A reliable supply of significant quantities of affordable IPV is also essential to polio eradication

Standalone full-dose Salk IPV will enabled the tOPV to bOPV switch and will enable bOPV cessation

Use of IPV in SIA campaigns and outbreak control demonstrates additional value of IPV to interrupt

transmission

2. Introduce

and Maintain

IPV in RI

Long-term needs may include larger commercial-scaled Salk or Sabin-based IPVs, potential dose-sparing

IPVs, IPV-containing combinations, microarray patches and other novel presentations

Potential for new adjuvants (e.g. DMLT) may have enhanced mucosal immunity impact

More genetically stable OPVs to lower VAPP or VDPV risk

3. Investigate

Novel

Products

Combo (IPV + Penta)

Improved Intestinal

Immunity Antiviral Program

Drive Coverage of IPV Low Cost Ease of Delivery LMIC Manufacturing

Mitigate Post-Eradication VDPV Risk

Sabin IPV

Enabling Activities

EPI Schedule

IPV Clinical Trials

Fractional Dosing

Intradermal Delivery

Intestinal Immunity

Sequential IPV-OPV

Novel Delivery Technologies

Environmental

Surveillance

EIA Antibody Assay

Modeling

Intestinal Immunity Assay

D-Antigen Standardization

Category Solution Tech Approach

Transmission

Antigen Sparing /

Improved Yield

© Bill & Melinda Gates Foundation | 19 © Bill & Melinda Gates Foundation | 19

THE FOUNDATION’S EFFORTS TO SUPPORT DEVELOPMENT OF BETTER VACCINES

IPV POST OPV CESSATION


SUMMARY AND LOOKING AHEAD


• Remarkable progress in 2016: o Lowest number of cases in lowest number of geographies

o Risks remain primarily due to inaccessibility / civil unrest in both

Afghanistan/Pakistan and Nigeria

• Strategic Priorities: o Surveillance

o Vaccine Supply

o Response Capacity (i.e. Outbreak response)

• Impact of future vaccine policy

• Innovations around vaccination schedules and delivery systems and their

programmatic adaptation will be key in achieving and sustaining success in

the coming years

THANK YOU


ipv use & challenges · source: gvmm, ipv supply update, 2016, bmgf analysis, october 2016...

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