COMMENTARY

Pneumococcal Immunization Strategies for Adults

Thomas M. File, Jr., MD

Disclosures

December 17, 2010

Determining the Optimal Pneumococcal Vaccination Strategy for Adults: Is There a Role for the Pneumococcal Conjugate Vaccine?

Metersky ML, Dransfield MT, Jackson LA
Chest. 2010;138:486-490

Background

Since the introduction of the 7-valent conjugate pneumococcal vaccine (PCV7) for children, invasive pneumococcal disease now affects adults disproportionately in the United States. This has occurred despite current vaccination recommendations that everyone 65 years of age and older as well as younger adults at high risk receive the 23-valent pneumococcal polysaccharide vaccine (PPV23).

Metersky and colleagues indicate that the recent approval of the 13-valent pneumococcal conjugate vaccine (PCV13) to replace PCV7 for children creates a unique situation, in that it is unusual to have a new pediatric vaccine for a disease that is also important in adults. They review preliminary evidence on the possible benefits of PCV13 in adults and address the questions this situation raises about how physicians and other practitioners might approach vaccination decisions to provide optimum protection for adults.

Study Summary

Evidence on the use of PCV13 in adults is limited, and the vaccine is not currently approved for use in this population. However, according to Metersky and colleagues, on the basis of what is known about PCV7 and PPV23, PCV13 may be a viable option for adults. In healthy adults, PPV23 is effective in preventing invasive pneumococcal disease, although it affords less robust protection in immunosuppressed persons. PPV23 does not seem to affect the risk for pneumonia in adults, whereas PCV7 seems to protect against pneumococcal pneumonia in children. Several studies that used surrogate markers for vaccine efficacy -- enzyme-linked immunosorbent assay and opsonophagocytic killing -- suggest that PCV7 elicits a superior immune response in adults compared with PPV23, especially when given at twice the usual pediatric dose. The investigators also note several lines of evidence suggesting that previous receipt of PPV23 may lead to a diminished antibody response to PCV7 (eg, immune hyporesponsiveness). In contrast, PCVs do not seem to inhibit subsequent responses to either conjugated or unconjugated vaccines.

A placebo-controlled trial of PCV13 (0.5 mL) in patients ≥65 years of age is currently being performed in the Netherlands. This study is likely to provide critical information about the protective effect of PCV13 against the outcome of vaccine-type pneumococcal pneumonia in adults, but the results are not anticipated to be available until 2012.

In the meantime, Metersky and colleagues acknowledge that some providers, if they are aware of the available yet limited data, may choose a different pneumococcal immunization strategy for at-risk adults than the currently recommended single dose of PPSV23 vaccination. Providers may decide to administer PCV13 to adults, followed by PPV23. Or, given that PPV23 may impair the response to PCV13, providers may decide to delay vaccination until PCV13 is approved for use in adults. The decision could depend on the patient's life expectancy, comorbidities, and risk for pneumococcal disease.

Another factor to consider is that whereas PCV13 incorporates the 7 serotypes of Streptococcus pneumoniae found in PCV7, as well as 6 additional strains known to cause disease, it covers 10 fewer serotypes than PPV23. The most recent data from the United States demonstrate that about 15% of invasive pneumococcal disease is caused by the 10 strains included in PCV23 but not PCV13. Thus, providers must balance the broader coverage offered by PPV23 against possible improved protection against a smaller number of strains with PCV13.

The investigators conclude that physicians and patients should be made aware of the information presented in this article to assist them in making decisions. At the same time, they suggest that advisory groups should not delay in analyzing available evidence and possibly formulating new policy for pneumococcal vaccination.

Viewpoint

Metersky and colleagues expertly review the issues underlying various strategies of pneumococcal vaccination for adults, particularly now that PCV13 is available for children and is anticipated to be approved for adults next year. This is of particular interest for clinicians who care for patients who are elderly or immunocompromised. Although PPV23 has been available for several decades, studies indicate that it is not as effective as we would like for elderly or immunocompromised patients, and even in immunocompetent adults, it does not necessarily prevent nonbacteremic pneumonia. This in part has led many clinicians to believe that PPV23 lacks efficacy and may be a reason why it is underutilized. However, there is general agreement that PPV23 does prevent invasive disease, such as bacteremia, and certainly reduces mortality in immunocompetent adults. Thus, we need to still promote this vaccine.

As Metersky and associates observed, PVC13 was recently introduced for use in children. The expanded coverage of serotypes is expected to further improve immunity in the pediatric population and especially target serotypes that have emerged as replacement types associated with use of the previous PCV7. Routine use of PCV7 in children since 2000 has led to waning disease incidence in this population, as well as reductions in invasive pneumococcal disease cases among older adults as a result of "herd immunity." It is perhaps ironic that PCV7 administered to children has been more beneficial in reducing invasive pneumococcal disease in adults than has direct vaccination of adults with PPV23. It is hoped that the use of PCV13 will increase this effect. However, we also know that the burden of disease is high in adults, and we need to increase appropriate vaccine use in adults at risk.

Metersky and colleagues raise the questions of whether PCV13 provides better effectiveness than PPV23 in older and immunocompromised adults, and if sequential administration is used, whether PCV13 should be administered before PPV23. The possible advantages of PCVs in immunocompromised and elderly adults may include greater protection against vaccine serotypes, longer duration of protection, and possible better protection against noninvasive pneumococcal disease.

Some of my colleagues are administering PCV off-label to their immunocompromised adult patients (especially those who have had transplant), with the rationale that it may provide better immune response and subsequently better effectiveness. Metersky and associates cite evidence suggesting a greater immunologic response if PCV is administered before PPV. We know that the conjugate vaccines activate B and T cells and generate immunologic memory, whereas polysaccharide vaccines activate only B cells and may not induce T-cell responses, and there is concern about "hyporesponsiveness." Whereas repeated doses of PCV usually result in a booster effect in which antibody levels are higher after subsequent dosing, repeated doses of PPV usually result in lower antibody levels compared with those associated with the initial dose. Therefore, administration of a first dose of PPV may blunt the immune response to subsequent doses ("immunologic hyporesponsiveness.") A recently published economic model suggested that PCV13 will be more cost effective in adults; however, the assumptions of this model can be questioned.[1]

Should PCV or PPV be considered for those approaching the age of indication (65 years) who do not have comorbid conditions? The large placebo-controlled study currently under way in The Netherlands will hopefully begin to answer this and other questions about the effectiveness of PCV13 in adults; its primary endpoint is prevention of pneumonia requiring admission to the hospital (not limited to invasive disease, as defined by presence of bacteremia).

I am personally interested because I, too, will soon reach the age of indication. Would it be better for me to receive PCV13 or PPV23 as my initial pneumococcal vaccine? The Netherlands study will give us some information to help with this decision, but until then, we can only rely on the immunogenicity studies and a few studies performed in special populations (such as HIV-infected individuals). It is possible that an initial dose of PCV13 followed by PPV23 (to enhance the number of serotypes covered) may provide better immunity and, more important, better effectiveness in disease reduction. For this reason, I am leaning toward this strategy rather than the use of PPV23 followed by PCV13.

Abstract

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