Use of 13-valent Pneumococcal
Conjugate Vaccine and 23-valent
Polysaccharide Vaccine in Adults with
Immunocompromising Conditions
Tamara Pilishvili, MPH
Respiratory Diseases Branch
National Center for Immunization & Respiratory Diseases,
CDC
5th Regional Pneumococcal Symposium
March 5-6, 2013
ACIP Recommendations for Use of Pneumococcal
Polysaccharide Vaccine (PPSV23) in Adults


All adults 65 yrs and older
Adults 19-64 years old with the following conditions
Advisory Committee on Immunization Practices (ACIP), MMWR 2010
Timeline for pneumococcal conjugate
vaccines in the U.S.
Recommendations
for PCV13
ACIP
Recommendations
for PCV7
ACIP
Feb 2000
Oct 2000
PCV7 licensed
for infants and
young children
FDA
Feb 2010
PCV13 licensed
(replaced PCV7)
FDA
FDA= Food and Drug Administration
ACIP=Advisory Committee on Immunization Practices
Recommendations
for PCV13 among
immunocompromised
adults
ACIP
Dec 2011
PCV13 licensed
for adults 50
years or older
FDA
Jun 2012
Jan 2013
PCV13 licensed for
children 6 through
17 years old
FDA
13-valent Pneumococcal Conjugate
Vaccine (PCV13) for Adults
•
•
•
•
Licensed for use among adults >50 years old on 12/30/11
FDA approved under the Accelerated Approval Pathway
Based on non-inferior immunogenicity compared to
PPSV23
Indications
• Prevention of pneumococcal disease (including pneumonia and
invasive disease) in adults 50 years of age and older
• Prevention of disease caused by Streptococcus pneumoniae
serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F
•
Post-approval condition of licensure: Randomized
controlled trial of PCV13 against pneumococcal pneumonia
among adults >65 years old in the Netherlands
Incidence of Invasive Pneumococcal Disease
among all adults, U.S., 2011
Cases per 100,000 persons
80
68
70
60
50
41
40
27
30
30
21
20
10
45
8
0
18-49
50-64
CDC, ABCs, unpublished, 2012
65-69
70-74
75-79
Age, years
80-84
85+
Estimated number of IPD cases and deaths in
the U.S., 2010
Cases
4,506
1,873
<5
5-17
18-49
50-64
65 or older
Deaths
57
43
666
15,296
10,342
2594
1474
11,847
Total cases=~44,000
Total deaths=~4,800
CDC unpublished data
ABCs 2010 incidence data; US 2009 post-census population estimates
6
Incidence of Invasive Pneumococcal Disease
Among Adults >65 Years by Serotype, 19982010
45
40
PCV7
introduced
35
30
25
20
15
10
5
0
ABCs unpublished data, continuous sites
PCV13
introduced
PCV7
PCV13/non-PCV7
Rank order of IPD serotypes among
Adults >65 years of age, 2010
Percent of invasive cases
14
Other types
PPV23 / NonPCV13 types
PCV13 types
12
10
8
6
4
2
0
19A
7F
3
22F
CDC, unpublished, 2010
6C
23A
9N
Serotype
35B
11A
16F
15A
8
PCV13 age-based recommendations:
U.S. ACIP Decision
At this time, the available evidence is insufficient to
recommend routine use of PCV13 among older adults
• Critical data elements for the ACIP recommendation
to be made are not available at this time
– the indirect effects of PCV13 use in children on
adult disease incidence
– results from the CAPITA trial
• Clinical relevance of immunogenicity data unclear
without defined correlate of protection
• Cost-effectiveness data relies heavily on assumptions
of efficacy against pneumonia and potential indirect
effects
Policy question considered by ACIP
Pneumococcal Working Group:
Should ACIP recommend PCV13 for
immunocompromised adults?
Incidence of IPD in adults aged 18--64 years with
selected underlying conditions, United States, 2009
200
186
20 fold increased risk
180
173
Cases per 100,000 persons
160
140
120
100
3-7 fold increased risk
80
52
60
59
41
40
20
26
28
32
8
0
HEALTHY
CVD
Kyaw, JID 2005;192:377-86
DIABETES PULMONARY
KIDNEY
LIVER
ALCOHOL
HIV/AIDS HEMATOLGICAL
CANCER
Trends in IPD rates among adults 18-64 yrs old
with & without HIV-infection,
before and after PCV7 introduction, 1998-2007
Adults with HIV
infection
Adults without HIV infection
6-8/ 100K
64 / 100K
Cohen, AIDS 2010;24(14):2253-62
Efficacy against Invasive Pneumococcal Disease
(IPD)
• IPD = isolation of pneumococcus from a normally sterile
site
• Double-blind, randomized, placebo-controlled
• Efficacy trial among HIV-Infected Adults in Malawi (N=496)
• All enrolled subjects had recovered from documented IPD
• 2 doses of PCV7 given 4 weeks apart
Endpoint
Vaccine Efficacy (95%
CI)
PCV7-serotype IPD
74% (30%, 90%)
French N, et.al. N Engl J Med 2010;362:812-22.
Summary: Immunogenicity of PCV in
immunocompromised adults




PCV does elicit an immune response in HIV+ and cancer
patients 1,2,3,4,5,6
Response following a single dose of PCV is as good or
better than PPV23 (both in vaccine naive or previously
vaccinated) 1,2,3
Studies with sequential vaccination show similar or
improved immune response if PCV given first 1,2,3
Revaccination with PCV show similar immunogenicity
compared to the first dose 4
1. Feikin Diag Lab Immunology 2004,
2. Lesprit AIDS 2007,
3. Penaranda AIDS 2010
4. Miro JID, 2005
5. Chan JID, 1996
6. Crum JID, 2010
In adults with immunocompromising conditions,
should we use PCV13, PPSV23 or Both?
Proportion of IPD by vaccine serotype, 2010
 21% of disease due to
serotypes in PPSV23 not
covered by PCV13
Immunocompromised
29%
50%
 Opportunity for broader
serotype protection
through use of BOTH
vaccines
21%
PCV13
PPV23/NonPCV13
CDC, ABCs, unpublished, 2011
Other
Conclusions for PCV13 among
Immunocompromised Adults
Extremely high burden of disease among
immunocompromised adults
 Indirect effects of PCV13 use in children unlikely to
eliminate PCV13 serotypes from
immunocompromised adults
 Benefits of PCV13 use in this group outweigh the
harms
 PCV13 alone may not provide adequate coverage of
serotypes causing disease
 Combined regimen of PCV13 and PPSV23 likely
better than either vaccine alone
ACIP Decision: Benefits likely outweigh harms and both
PCV13 and PPSV23 should be recommended for adults with
immunocomromising conditions

PCV13 and PPSV23:
Vaccination Sequence

Data for PCV followed by PPSV
 3 studies in HIV+ show that antibodies non-inferior or superior
when PCV given prior to PPSV
 Phase III studies in immunocompetent show that
PCV13 + PPSV23 > PPSV23 + PCV for 11/12 serotypes

Data for PPSV followed by PCV
 In 1 study in HIV+ in Uganda, PPSV 5 yrs prior did not affect
response to PCV
 In 1 study in HIV+ in US, there was no difference in
immunogenicity between PCV and PPSV given 3-8 years after
PPSV
Data support use of PCV13 followed by PPSV23
PCV13 and PPSV23:
Interval between vaccines

What is the optimal interval between PCV and PPSV?
 HIV+ @ 1 & 2 month intervals
 Immunocompetent older adults
@ 6 and 12 month intervals

All intervals showed significant
increases in antibody as well
as non-inferior or superior
response compared to PPSV
alone
What is the optimal interval between PPSV and PCV?
 Studies in immunocompetent suggest blunting of immune
response <5 years after PPSV
 No evidence of reduced immunogenicity in HIV+ with
PCV 5 years after PPSV

No studies have been designed to evaluate the
optimal interval
Recommendation for PCV13 and PPSV23

Vaccine naïve adults:
 PCV13 dose is recommended to be given before PPSV23,
whenever possible
 PPSV23 should be given at least 8 weeks after a dose of
PCV13
 Recommendations for 2nd dose of PPSV and a dose at age
65 years or older remain unchanged

PPSV23-immunized adults
 A dose of PCV13 is recommended to be given to adults with
immunocompromising conditions who received 1 or more
doses of PPSV23 1 or more years after the last PPSV23
dose
 Total number and interval between PPSV23 doses
unchanged from current recommendations
19
Indications for PCV13 and PPSV23
Advisory Committee on Immunization Practices, MMWR 2012
Prevention of pneumococcal disease among adults with
immunocompromising conditions
Recommendation for PPSV23-naïve adults
PCV – PPSV – PPSV*
>8 weeks
+ PPSV (@ 65 years or later)
>5 years
Integrating new PCV13 recommendation for adults previously
vaccinated with PPSV23
>5 years
1)
PPSV – PCV – PPSV*
>1 year
2)
3)
PPSV (@ 65 years or later)
>8 weeks
PPSV – PPSV*- PCV
>5 years
+
>1 year
PPSV –PPSV*
+
+ PPSV (@ 65 years or later)
>1 year
PPSV (@ 65 +) – PCV
>5 years
*Second PPSV dose before age 65 years NOT recommended for adults with CSF leaks or those with
cochlear implants
21
Acknowledgements
ACIP members
CDC
Nancy Bennett (Chair)
Wendy Keitel
Jeffrey Duchin
Michael Marcy
Ex Officio members
Mark Grabowsky
Kristin Nichol
Lucia Lee
Tamara Pilishvili
Cynthia Whitney
Matt Moore
Kathleen Dooling
Tom Hennessy
Sandra Steiner
Gina Mootrey
William Atkinson
Jorge Arana
Maria Cano
Erin Kennedy
Carolyn Bridges
Charles LeBaron
Liaison representatives
Lorry Rubin
Rick Zimmerman
William Schaffner
Caroline Quach
Ken Gershman
Daniel Musher
Mary Glode
Jane Zucker
Lisa Jackson
Monica Farley
Kathy Neuzil
Julie Morita
Anthony Brenneman
Sandra Fryhofer
The findings and conclusions in this report are those of the authors and do not necessarily represent the official
position of the Centers for Disease Control and Prevention.
National Center for Immunization & Respiratory Diseases
Division of Bacterial Diseases