Curr Emerg Hosp Med Rep (2015) 3:121125

DOI 10.1007/s40138-015-0078-6

COPD (J. FANIKOS, SECTION EDITOR)

Review of Current Pneumococcal Vaccine Guidelines

Komal Bawa1 Megan Pintens2

Published online: 16 June 2015

 Springer Science+Business Media New York 2015

Abstract Pneumococcal vaccination has been associated

with a decline in the infectious disease burden caused by
Streptococcus pneumoniae since it was incorporated into
routine vaccination schedules for adults and children. In
2014, the Centers for Disease Control and Prevention
updated its recommendations to include a single dose of a
13-valent pneumococcal conjugate vaccine for adults
C65 years. The pediatric recommendations remain
unchanged. This paper reviews the current vaccine recommendations for adults and children.
Keywords Pneumococcal vaccine
Invasive
pneumococcal disease
Immunization
Pneumococcal
conjugate vaccine [PCV13]
Pneumococcal
polysaccharide vaccine-23 [PPSV23]

Introduction
Streptococcus pneumoniae (pneumococcus) is implicated
as a leading cause of infection including sinusitis, otitis
media, pneumonia, meningitis, and bacteremia. These
serious illnesses primarily affect young children
This article is part of the Topical Collection on COPD.
& Komal Bawa
Komal.bawa@gmail.com
Megan Pintens
mpintens@gmail.com
1

Medical Communications, Genentech, 1 DNA Way,

South San Francisco, CA 94080, USA
Pharmacy Department, University of California San
Francisco, Box 0622, 521 Parnassus Avenue, Room C-152,
San Francisco, CA 94122, USA

(\2 years), older adults (C65 years), and those with

immunocompromising conditions. In 2013, there was an
estimated 33,500 cases of invasive pneumococcal disease
(IPD), accounting for 3500 deaths in the United States [1].
A 14-valent pneumococcal polysaccharide vaccine was
first licensed in the United States in 1977 for use in children C2 years of age at increased risk for pneumococcal
disease [2]. The original vaccine was replaced by the
currently available 23-valent pneumococcal polysaccharide
vaccine (PPSV23) in 1983 [2]. Given that polysaccharide
vaccines have been shown to be poorly immunogenic in
children, the Food and Drug Administration (FDA)
licensed a 7-valent pneumococcal conjugate vaccine
(PCV7) in February 2000. Since this time the Centers for
Disease Control and Prevention (CDC) has recommended
routine vaccination against S. pneumoniae in infants and
young children [3]. The pneumococcal serotypes covered
by PCV7 included 4, 6B, 9V, 14, 18C, 19F, and 23F.
Routine use of PCV7 resulted in a decline in the incidence
of IPD both directly in children and indirectly in adults [4].
In 2010, a 13-valent pneumococcal conjugate vaccine
(PCV13) replaced the PCV7 used in childhood vaccination
schedules. As a result, the incidence of IPD in adults
C65 years caused by serotypes included in PCV13
decreased by about 50 % in 2013 compared with 2010 [5,
6]. PCV13 includes the serotypes found in PCV7 and 6
additional serotypes (1, 3, 5, 6A, 7F, and 19A).

Pneumococcal Vaccination in Adults

The FDA approved PCV13 for use in adults C50 years in
late 2011, but use in this patient population was not well
defined at the time. On June 20, 2012, the Advisory
Committee on Immunization Practices (ACIP) updated

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their recommendations on pneumococcal vaccination in

adults aged C1964 with immunocompromising conditions, cerebrospinal fluid (CSF) leaks, functional or anatomic asplenia, or cochlear implants to include PCV13 [7].
Patients with these conditions who are pneumococcal
vaccine-nave should receive PCV13 for one dose, followed by PPSV23 at least 8 weeks later [7]. Patients with
immunocompromising conditions, CSF leaks, asplenia, or
cochlear implants who were previously vaccinated with
PPSV23 should receive PCV13 for one dose C1 year after
the most recent dose of PPSV23 [7]. Individuals requiring
an additional dose of PPSV23 should receive the follow-up
dose no sooner than 8 weeks after PCV13 and C5 years
after the previous PPSV23 dose [7].
In order to comply with the accelerated approval
requirements through the FDA, Pfizer conducted a randomized, placebo-controlled trial (CAPiTA) to determine
the clinical benefit of PCV13 for the prevention of vaccinetype (VT) pneumococcal community-acquired pneumonia
(CAP) [8]. The study was conducted in the Netherlands
from 2008 to 2013 in approximately 85,000 adults aged
C65 years who were previously unvaccinated for pneumococcal disease [8]. The results from the CAPiTA trial
became available in June 2014 and demonstrated vaccine
efficacy of 45.6 % for the prevention of VT-CAP, 45 %
efficacy for the prevention of VT nonbacteremic pneumococcal pneumonia, and 75 % efficacy for the prevention of
VT-IPD [8].
Two randomized, modified double-blind immunogenicity studies have been conducted in adults 6064 years of age
and C70 years of age to assess the effectiveness of PCV13
versus PPSV23 [9, 10]. Adults aged 6064 who were
pneumococcal vaccine-nave were randomized to receive
either the PCV13 or PPSV23 [9]. Opsonophagocytic activity
(OPA) titers were assessed at 1-month post-vaccination [9].
OPA geometric mean titers (GMTs) were comparable
between PCV13 and PPSV23 for the 12 serotypes common
to both vaccines and statistically significantly greater for 8 of
the 12 common serotypes [9]. In adults C70 years of age
who were previously vaccinated with PPSV23 at least
5 years prior, a dose of either PCV13 or PPSV23 was
administered, with an additional dose of PCV13 administered to all subjects 1 year after the initial dose at enrollment
[10]. One month after the initial dose of either PCV13 or
PPSV23, OPA GMTs of the 12 common serotypes were
again comparable between groups and statistically significantly greater for 10 of 12 common serotypes in the PCV13
group [10]. One month after the follow-up dose of PCV13,
OPA GMTs were statistically significantly lower for all 13
serotypes in subjects who received PPSV23 initially compared to those who received PCV13 [10].
An immunogenicity study evaluating the immune
response to pneumococcal vaccine found that OPA titers

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1 month after PPSV23 administration which was given

1 year after an initial PCV13 dose were statistically significantly higher for 6 of the 12 common serotypes than
OPA titers achieved following only the initial PPSV23
dose [11]. Additionally, OPA titers were statistically significantly higher for 11 of the 12 common serotypes when
PCV13 was given initially followed by PPSV23 1 year
later compared with PPSV23 administration followed by
PCV13 at 1 year [11].
Given the results from the CAPiTA trial and the above
immunogenicity data, the ACIP updated its recommendations for pneumococcal vaccination in adults C65 years old
on August 13, 2014 [5]. The recommendations now
include the routine use of both PCV13 and PPSV23 in
adults C65 years. Adults C65 years who are pneumococcal
vaccine-nave should receive PCV13 followed by a dose of
PPSV23 in 612 months, with at least 8 weeks between
PCV13 and PPSV23 [5]. PCV13 and PPSV23 should not
be given concomitantly [5]. Adults C65 years who have
previously been vaccinated with at least one dose of
PPSV23 should receive a dose of PCV13 to be given
C1 year after the most recent PPSV23 dose [5]. In individuals who require an additional dose of PPSV23, it should
be administered 612 months after PCV13 and C5 years
after their previous dose of PPSV23 [5]. See Fig. 1.
PPSV23 (Pneumovax 23) and PCV13 (Prevnar 13)
are both available in the United States for intramuscular
injection as a 0.5 mL dose [2, 3]. PPSV23 can be
administered subcutaneously as well. PCV13 may be coadministered with trivalent inactivated influenza vaccine
(TIV), however, there are no data regarding administration
of PCV13 with any other available vaccines in adults [5].

Pneumococcal Vaccination in Pediatric

PCV7 was shown to be highly efficacious and safe at
preventing IPD and potentially decreasing otitis media
cases in children. One study showed 97.4 % efficacy
against IPD caused by PCV7 serotypes in fully vaccinated
infants [12].
Prior to routine vaccination, S. pneumoniae reportedly
led to about 17,000 cases of IPD each year among children
\5 years of age, including 700 cases of meningitis and 200
deaths [13]. Subsequent to this change in practice, IPD has
decreased by 6090 % in children \2 years. The active
bacterial core surveillance (ABCs) system has shown the
frequency of IPD in children\5 years has dropped from 99
cases/100,000 patients to 21 cases/100,000 patients from
1998 to 2008, respectively. The 2008 ABC data showed
approximately 61 % of IPD cases were caused by serotypes
that PCV13 covers, with serotype 19A causing 43 % of
these cases [3].

Curr Emerg Hosp Med Rep (2015) 3:121125

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serotypes which account for 23 % of IPD in immunocompromised children aged 618 years [16]. Routine
vaccination with polysaccharide vaccines are not recommended in children B2 years as they are poorly immunogenic [17].
Children C2 years with underlying immunocompromising diseases, CSF leaks, functional or anatomic asplenia, or chronic medical conditions are considered to be at
increased risk of IPD from serotypes contained in PPSV23
[3]. After completing the PCV13 series, PPSV23 should
be administered after a minimum of 8 weeks. Children
with immunocompromising conditions or functional or
anatomical asplenia should be revaccinated with PPSV23
5 years after the initial dose.

Safety

Fig. 1 Advisory Committee on Immunization Practices recommendations for PCV13 and PPSV23 for adults age C65 years. From:
Reference [5].

Children with a congenital or acquired immunodeficiency, HIV infection, an abnormal innate immune
response, or compromised splenic function are considered
to be at highest risk of IPD [13]. Those with cochlear
implants are at increased risk of pneumococcal meningitis
[14].
PCV13 has been safely administered in combination
with other routine childhood vaccinations. Concurrent
vaccinations include diphtheria, tetanus, acellular pertussis,
Haemophilus
influenzae,
rotavirus,
inactivated
poliomyelitis, hepatitis B, meningococcus, measles,
mumps, rubella, and varicella [15]. Table 1 summarizes the
ACIP recommendations for pneumococcal vaccination
based on age group. The minimum interval between vaccine doses is 8 weeks, unless the child is younger than
12 months. If younger than 12 months, the minimum
interval is 4 weeks between vaccinations. Routine vaccination of children C5 is not recommended [3].
Additionally, since 2000 ACIP has recommended children C2 years with certain medical conditions receive
PPSV23, in addition to PCV13 [13, 16]. PPSV23 contains
the serotypes found in PCV13 and an additional 11

The pneumococcal polysaccharide and conjugate vaccines

are generally well tolerated with few major safety issues
identified [5, 9, 18]. The following common adverse
reactions were noted for PPSV23: injection-site reactions,
headache, asthenia or fatigue, and myalgia. Injection-site
reactions were reported most frequently (60 %) [19]. One
study showed increased injection-site reactions after
revaccination (79.3 %) than after initial vaccination
(52.9 %) in adults [65 years [19]. More than 6000 adults
C50 years received a dose of PCV13 during the drug trials
evaluating the vaccine. These patients were both PPSV23
nave and experienced [20]. Local reactions including pain
at injection site, swelling, limitation of movement, and
redness were the most frequently occurring adverse reactions associated with PCV13 [5, 20].
The safety of PCV13 has been assessed across 13 clinical trials among 4729 children [3]. Common adverse
reactions seen within 7 days of vaccination included
injection-site reaction, fever, decreased appetite, changes
in sleep and irritability [15]. A small increase in hospitalizations secondary to reactive airway disease was observed
from clinical trials which a follow-up study failed to show
[12, 21]. Data obtained from the Vaccine Adverse Event
Reporting System (VAERS) showed that most adverse
events were described as minor. A surveillance study of
VAERS showed rates of serious adverse events (14.6 %)
were similar to other vaccines (14.2 %) [22].

Conclusion
Streptococcus pneumoniae is responsible for serious illnesses that affect young children, older adults, and those
with immunocompromising conditions. While the currently
available vaccines (PPSV23 and PCV13) do not include all

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Curr Emerg Hosp Med Rep (2015) 3:121125

Table 1 Advisory Committee on Immunization Practices recommendations for PCV13 and PPSV23 schedule in unvaccinated children
Age at first dose

PCV13 series

PCV13 booster

PPSV23

26 months*

3 Doses

1 dose at 1215 months

711 months

2 Doses

1 dose at 1215 months

1223 months

2 Doses

2459 months (healthy children)

1 Dose

2471 months (chronic illness or immunocompromised)

2 Doses

1 Dose

1 Dose

1 Dose

618 years (with high risk conditions)

a

No previous vaccination with PCV13

* Minimum age at first immunization is 6 weeks

Second dose 5 years after first dose in immunocompromised children

pneumococcal serotypes, they cover the most prevalent

serotypes that are responsible for causing upwards of 80 %
of disease [3]. ACIP recommends routine vaccination in
children, older adults, and those with immunocompromising conditions.
Compliance with Ethics Guidelines
Conflict of Interest
of interests

The authors declare that they have no conflicts

Human and Animal Rights and Informed Consent This article

contains no studies with human or animal subjects performed by the
author.

References
Papers of particular interest, published recently, have been
highlighted as:
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