pneumococcal vaccine.

1. Dr HAFSA M
1st year DTCD resident
PNEUMOCOCCAL VACCINATION

2. INTRODUCTION
 Important preventive health care measure that
reduces the burden of pneumococcal disease in
vaccinated individuals and in the population.
 Pneumococcal vaccination is indicated for adults
with risk factors for pneumococcal disease or for
severe adverse outcomes should disease occur.
 Pneumococcal vaccination is also a routine part
of infant and childhood immunization schedules
worldwide.

3. VACCINE TYPES
 Two types:
 Pneumococcal polysaccharide vaccine (PPSV)
 Pneumococcal conjugate vaccine (PCV)
 The active components of both kinds of vaccine
are capsular polysaccharides from pneumococcal
serotypes that commonly cause invasive disease.

4. Polysaccharide vaccines
 PPSV is composed of partially purified
pneumococcal capsular polysaccharides.
 The only available formulation contains 23
pneumococcal polysaccharides (PPSV23;
Pneumovax or Pnu-Immune)

5. Conjugate vaccines
 PCVs consist of pneumococcal capsular
polysaccharides covalently linked (conjugated) to a
protein.
 Different carrier proteins have been used for
conjugation, the most common being CRM197, a
nontoxic, genetically altered variant of diphtheria
toxin.
 10-valent PCV (PCV10; Synflorix), the 13-valent PCV
(PCV13; Prevnar 13), the 15-valent PCV (PCV15;
Vaxneuvance), and the 20-valent PCV (PCV20;
Prevnar 20), with the numbers indicating the number
of pneumococcal capsule types included in the
vaccine.
 The 7-valent PCV (PCV7; Prevnar 7) is an older
formulation that is no longer produced.

6.  PCV stimulates mucosal immunity, thereby preventing
nasal colonization of Streptococcus pneumoniae.
 Mucosal immunity leads to two population-level effects: (1)
indirect (herd) immunity and (2) emergence of replacement
strains.
 With widespread use of PCV in infants and children,
pneumococcal transmission decreases and thus lends
protection to unvaccinated individuals (including adults).
 As a result, with the exception of serotypes against which
the vaccines are not effective, serotypes present in PCV7
and then in PCV13 have nearly disappeared from the
pediatric and adult populations.
 However, as these serotypes disappear, new
pneumococcal serotypes emerge to occupy the vacant
ecologic niche; these are called “replacement strains.

7. Comparison of properties of the pneumococcal
polysaccharide and conjugate vaccines
Polysaccharide
vaccine
Conjugate
polysaccharide
vaccine
Stimulates antibodies
in infants and toddlers
No Yes
Stimulates antibodies
in healthy adults
Yes Yes
Stimulates antibodies
in
immunocompromised
adults
+/- +/-
Antibodies are long-
lasting
+/- +/-
Primes
immunologically for
enhanced responses
No Possibly
Stimulates mucosal
immunity, resulting in
decreased
colonization
No Yes
Exhibits herd effect
(secondary protection
of unvaccinated
No Yes

8. Indications for vaccination
The goal of vaccination in adults is to prevent
invasive pneumococcal disease (IPD; eg,
bacteremic pneumonia, meningitis) and
nonbacteremic pneumonia.
 All adults ≥65 years of age
 Adults aged 19 to 64 years with:
 Predisposing chronic medical conditions (eg,
chronic lung disease, chronic liver disease,
diabetes mellitus)
 Increased risk of meningitis (eg, cochlear implant,
cerebrospinal fluid [CSF] leak)

9.  Immunocompromising conditions (eg, human
immunodeficiency virus [HIV] infection,
hematologic malignancies) and other conditions
associated with altered immunocompetence
(functional or anatomic asplenia, chronic renal
disease, and nephrotic syndrome)
 Functional or anatomic asplenia

10.  These populations are at increased risk of
developing IPD and/or are at higher risk of
morbidity and mortality from IPD.
 While there is evidence that many patients with
immunocompromising conditions such as
lymphoma or multiple myeloma are unlikely to
develop antibody following vaccination with
pneumococcal conjugate vaccines (PCV)
or pneumococcal polysaccharide vaccine (PPSV).

11. Vaccine selection
 Approach to healthy older adults and those
with predisposing medical conditions —
 The ACIP recommends the 20-valent PCV
(PCV20) alone or the 15-valent PCV (PCV15)
followed by the 23-valent PPSV (PPSV23) for all
adults with indications for vaccination .
 For most adults, including healthy older adults,
those with predisposing medical conditions, and
those with a history of IPD, its prefer to administer
PCV20, when available, due to the simplicity and
lower cost of a single-dose vaccine. Comparative
efficacy of these two approaches is unknown.

12.  If PCV20 is not available, PCV15 followed by
PPSV23 is a recommended alternative.
 If PCV15 is administered, PPSV23 should be
administered one year after PCV15 to provide
immunity against an increased number of
pneumococcal serotypes.
 When the series PCV15 followed by PPSV23 is
completed, protection is offered to an additional
three serotypes compared with the single PCV20
approach.
 Although it is hypothesized that the
immunogenicity of PPSV is boosted by prior
administration of PCV, this booster effect has not
been convincingly demonstrated.

13. Approach to individuals at highest
risk of pneumococcal disease
 For immunocompromised individuals and those at
increased risk for meningitis, the authors prefer to
administer PCV20 followed by PPSV23 ≥8 weeks
later.
 This recommendation differs from the ACIP and other
experts’ recommendations to administer PCV20 alone
(or PCV15 followed by PPSV23) in these populations.
 The authors administer the PPSV23 in addition to
PCV20 in these individuals to provide protection
against serotypes present in PPSV23 that are absent
from PCV20.
 Although PCV20 covers the majority of the serotypes
implicated in IPD, there are three relatively common
serotypes (9N, 20, 17F) included in PPSV23 that are
not included in PCV20

14. Approach to recipients of prior
pneumococcal vaccines
 The approach to complete the pneumococcal
vaccination series for individuals who have
already received pneumococcal vaccination
depends on the specific vaccine they received
 PPSV23 only − Adults who have only received
the PPSV23 vaccine should receive PCV20 (or
PCV15 if PCV20 is not available) at least a year
after PPSV23.
 PCV13 only − Adults who have only received
PCV13 should receive PCV20 (or PPSV23 if
PCV20 is not available) at least one year after
receipt of PCV13 . A shorter interval for PPSV23
of ≥8 weeks is recommended for those at highest
risk for pneumococcal disease.

15.  Both PCV13 and PPSV23
 Adults ≥65 years of age:
 Those who received both the PCV13 and PPSV23
prior to age 65 years should receive PCV20 or
PPSV23 (if PCV20 is not available) ≥5 years after
their last pneumococcal vaccine dose.
 Those who received PCV13 at any age and PPSV23
at ≥65 years of age, the ACIP advises shared
decision-making between clinician and patient
regarding whether to administer PCV20 ≥5 years after
their last pneumococcal vaccine.
 The authors of this topic prefer to administer PCV20
(or PPSV23 if PCV20 is not available) ≥5 years after
the patient’s last pneumococcal vaccine since the
benefits generally outweigh the minimal risks of an
adverse vaccine reaction.

16.  Adults aged 19 to 64 who have already received
both PCV13 and PPSV23 should receive PCV20
(or PPSV23 if PCV20 is not available) five years
after their last pneumococcal vaccination.
 Although the ACIP does not recommend a
second dose of PPSV23 to those with increased
risk for meningitis the authors of this topic believe
the benefits of a second PPSV23 dose (when
PCV20 is not available) outweigh the minimal
risks of an adverse vaccine reaction.
 Those who have received PCV13 and two doses
of PPSV23 should receive PCV20 five years after
their last pneumococcal vaccination, if available.

17. General approach to
revaccination
 The approach to revaccination varies among
experts and clinical practice guidelines.
 The ACIP does not recommend additional doses
of pneumococcal vaccines beyond those
discussed above.
 In contrast, the authors offer repeat vaccination
with PPSV23 every 5 to 10 years to all adults who
received an older formulation of PCV (eg,
PCV13) and PPSV23.
 For patients who have received PCV20 alone,
PCV20 in series with PPSV23, or PCV15 in
series with PPSV23, no revaccinations are
necessary .

18.  The authors’ recommendation for revaccination every
5 to 10 years is based on in vitro studies that show
waning of antibody and field studies that show waning
effectiveness after vaccination with PPSV23.
 Although data on duration of antibody and
effectiveness after receipt of PCV are not available
beyond five years, any difference in
opsonophagocytic effect between PPSV23 and
PCV13 is no longer detectable after 12 months.
 The authors suspect that no pneumococcal vaccine
will provide lifetime protection and believe the
potential benefits of repeat revaccination with
PPSV23 every 5 to 10 years greatly outweigh the
risks.
 Since there are no data on revaccination with PCV,
the authors only revaccinate with PPSV23

19. VACCINE ADMINISTRATION
 Dose and route — Pneumococcal vaccines are
administered intramuscularly as a 0.5 mL dose.
 Administration with other vaccines —
Pneumococcal vaccines generally may be given
concomitantly with other nonpneumococcal
vaccines .
 When more than one vaccine is given, they
should be administered with different syringes
and at different injection sites.

20. SAFETY
 Adverse effects — The immune response to pneumococcal
vaccination can elicit a clinically apparent inflammatory response
at the injection site and systemically.
 While most adverse effects associated with vaccination are not
severe and are self-limited, all should be reported.
 Injection site reactions — Injection site reactions are the most
common adverse effects associated with pneumococcal
vaccination in adults.
 For PPSV23, pain and tenderness at the injection site occur in
over half of vaccines, swelling and/or induration in approximately
20 percent, and redness in approximately 15 percent. Rates are
similar for pneumococcal conjugate vaccines.
 In some, these symptoms limit arm movement.
 Injection site reactions usually resolve spontaneously over three
to four days. Nonsteroidal anti-inflammatory drugs and warm
compresses can help relieve pain.

21. Other adverse effects
 Systemic symptoms (eg, fever, chills, fatigue,
headache, myalgias, arthralgias) can also occur
following vaccination . While fever (temperature
≥38°C) occurs in less than 5 percent, other
systemic symptoms occur frequently but are
usually mild. Like injection site reactions,
systemic symptoms following vaccination are self-
limited.
 Contraindications — Vaccination is
contraindicated for patients who have a history of
severe allergic reactions (eg, anaphylaxis) to
either pneumococcal vaccine or any of its
components (eg, diphtheria toxoid for PCV).

22. RATIONALE FOR VACCINATION
 Burden of disease — S. pneumoniae is the
leading bacterial cause of pneumonia worldwide
. Other manifestations of pneumococcal infection
include meningitis, bacteremia of undetermined
source, acute purulent sinusitis, and otitis media.
These pneumococcal infections cause substantial
morbidity and mortality.

23. Immunogenicity
 Both the PPSV23 and PCV are immunogenic in
adults.
 Numerous studies have compared responses with
polysaccharide and conjugate vaccines and
demonstrated no consistent differences in
immunogenicity between the two vaccine types.
 The response to pneumococcal vaccine in adults is
measured by the rise in antibody levels and/or serum
opsonic (phagocytic) activity after vaccine
administration.
 Antibody responses may be reported as mean
immunoglobulin (Ig)G levels or opsonophagocytic
titers (the dilution at which serum shows an
opsonizing [phagocytic] effect).
 Opsonophagocytic titers are thought to be a better
indication of protective immunity because IgG
generated by older and more frail adults may be less

24. Vaccine efficacy
Polysaccharide vaccine — PPSV23 has been
shown to be effective in preventing IPD and
pneumococcal pneumonia .

25. COST EFFECTIVENESS
 Administration of PCV20 alone or the 15-valent PCV
in series with the PPSV23) to all adults ≥65 years
appears to be cost-effective when compared with the
prior recommendations.
 Although evaluated by different models, PCV20 alone
was more cost-effective than PCV15 followed by
PPSV23.
 Models included indirect effect and waning of
effectiveness. The expected decline in disease due to
PCV20 types in adults once this conjugate vaccine is
recommended for widespread use in infants and
toddlers will almost certainly render the use of PCV20
in adults less cost-efficient.