Navigating pneumococcal vaccination in adults

From Cleveland Clinical Journal of Medicine 2016 Jun;83(6):427-433.

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With two nonequivalent vaccines available and different recommendations for different patient populations, vaccination against Streptococcus pneumoniae can be confusing. Here we try to clarify the situation.


  • At highest risk of invasive pneumococcal disease are people who are immunocompromised, very young, or very old.
  • Pneumococcal polysaccharide vaccine-23 (PPSV23) covers more serotypes of S pneumoniae than pneumococcal conjugate vaccine-13 (PCV13), but the latter induces a stronger antibody response.
  • The combination of both vaccines in sequence produces a better antibody response than either vaccine alone.
  • The Advisory Committee on Immunization Practices now recommends that immunocompromised and asplenic adults who need pneumococcal vaccination receive both vaccines, preferably PCV13 first, followed by PPSV23 8 weeks later. Those who have already received PPSV23 can receive PCV13 after at least 1 year has passed.
  • People with asplenia or immunocompromising conditions should receive a second dose of PPSV23 at least 5 years after the first dose.
  • Vaccination schedules and information are available from the US Centers for Disease Control and Prevention at



STREPTOCOCCUS PNEUMONIAE (the “pneumococcus”) causes a variety of clinical syndromes that range from otitis media to bacteremia, meningitis, and pneumonia. Hardest hit are immunocompromised people and those at the extremes of age. Therefore, preventing disease through pneumococcal vaccination is very important in these groups.

This review summarizes the current guidelines from the Advisory Committee on Immunization Practices (ACIP) of the US Centers for Disease Control and Prevention (CDC) for pneumococcal immunization in adults.


Invasive pneumococcal disease is defined as infection in which S pneumoniae can be found in a normally sterile site such as the cerebrospinal fluid or blood, and it includes bacteremic pneumonia.1 By far the most common type of pneumococcal disease is pneumonia, followed by bacteremia and meningitis (Figure 1);2,3 about 25% of patients with pneumococcal pneumonia also have bacteremia.2

Invasive pneumococcal disease most often occurs in children age 2 and younger, adults age 65 and older, and people who are immunocompromised. In 2010, the incidence was 3.8 per 100,000 in people ages 18 to 34 but was 10 times higher in the elderly and those with compromised immunity.1

Even now that vaccines are available, invasive pneumococcal disease continues to cause 4,000 deaths per year in the United States.1


S pneumoniae is a gram-positive coccus with an outer capsule composed of polysaccharides that protect the bacterium from being ingested and killed by host phagocytic cells. Some 91 serotypes of this organism have been identified on the basis of genetic differences in capsular polysaccharide composition.

Currently, two inactivated vaccines are available that elicit antibody responses to the most common pneumococcal serotypes that infect humans.

  • PPSV23 (pneumococcal polysaccharide vaccine-23, or Pneumovax 23) contains purified capsular polysaccharides from 23 pneumococcal serotypes.
  • PCV13 (pneumococcal conjugate vaccine-13, or Prevnar 13) contains purified capsular polysaccharides from 13 serotypes that are covalently bound to (conjugated with) a carrier protein.


Apart from the number of serotypes covered, the two vaccines differ in important ways. Both of them elicit a B-cell-mediated immune response, but only PCV13 produces a T-cell-dependent response, which is essential for maturation of the B-cell response and development of immune memory.

FIGURE 1. Incidence of pneumococcal disease in adults age 50 and older in the United States.Information from references 2 and 3.

PPSV23 generally provides 3 to 5 years of immunity, and repeat doses do not offer additive or “boosted” protection. It is ineffective in children under 2 years of age.

Pneumococcal conjugate vaccine has been available since 2000 for children starting at 2 months of age. Since then it has directly reduced the incidence of invasive pneumococcal disease in children and indirectly in adults. The impact on pneumococcal disease rates in adults has probably been related to reduction in rates of pneumococcal nasopharyngeal carriage in children, another unique benefit of conjugated vaccines.3

In December 2011, the US Food and Drug Administration (FDA) approved PCV13 for adults on the basis of immunologic studies and anticipation that clinical efficacy would be similar to that observed in children.


The efficacy and safety of PPSV23 and PCV13 have been studied in a variety of patient populations. Though antibody responses to PCV13 were similar to or better than those with PPSV23, no studies of specific correlations between immunologic responses and disease outcomes are available.4,5

In large studies in healthy adults, both vaccines reduced the incidence of invasive pneumococcal disease. A study in more than 47,000 adults age 65 and older showed a significant reduction in pneumococcal bacteremia (hazard ratio 0.56, 95% confidence interval 0.33–0.93) in those who received PPSV23 compared with those who received placebo.6 However, PPSV23 was not effective in preventing nonbacteremic and noninvasive pneumococcal community-acquired pneumonia when all bacterial serotypes were considered.6

In a placebo-controlled trial in more than 84,000 people age 65 and older, PCV13 prevented both nonbacteremic and bacteremic community-acquired pneumococcal pneumonia due to serotypes included in the vaccine (relative risk reduction 45%, P < .007) and overall invasive pneumococcal disease due to serotypes included in the vaccine (relative risk reduction 70%, P < .001).7

Both vaccines have also demonstrated efficacy in immunocompromised adults. Several studies showed an equivalent or superior antibody response to a seven-valent pneumococcal conjugate vaccine (PCV7, which has been replaced by PCV13) compared with PPSV23 in adults with human immunodeficiency virus (HIV) infection.8,9 While specific clinical studies of the efficacy of PCV13 among immunocompromised people are not available, a study of vaccination with PCV7 in 496 people in Malawi, of whom 88% were infected with HIV, found that the vaccine was effective in preventing invasive pneumococcal disease (hazard ratio 26%, 95% confidence interval 0.10–0.70).10

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