Pneumococcal Vaccination Among Adults With Chronic Respiratory Diseases

A Historical Overview

Angel Vila-Corcoles; Olga Ochoa-Gondar

Disclosures

Expert Rev Vaccines. 2012;11(2):221-236. 

In This Article

Polysaccharide Pneumococcal Vaccines

The first suggestion of an antipneumococcal vaccine appeared in 1911, when it was suggested that the inoculation of killed whole pneumococci might induce a protective effect against pneumococcal infections.[34] However, the key finding for an effective vaccination strategy was the isolation of pneumococcal capsular polysaccharides in 1926.[35] Five years later, an earlier polysaccharide-based pneumococcal vaccine (PPV) proved its effectiveness by successfully terminating a hospital outbreak of pneumonia in Massachusetts (USA).[36]

The first large trial assessing the efficacy of a PPV was published in 1947 by Kaufman et al., who reported a significant protective effect of a trivalent vaccine in preventing pneumonia among institutionalized older adults in New York (USA).[37] During the next decades, the interest for the vaccine decreased owing to the development of successful antibiotic therapy against pneumococcus.[38] However, the appearance of antibiotic resistance and the persistence of fatal invasive pneumococcal infections renewed interest in vaccine strategies and 6- and 12-valent PPV were synthesized and evaluated among novice gold miners in South Africa during the 1970s.[39] New efforts resulted in the production of a 14-valent PPV by Austrian and coworkers in 1976.[40] The currently available 23-valent PPV was licensed in 1983.[31]

The 23-valent vaccine includes 25 mg purified capsular polysaccharide antigens from each of the 23 serotypes (serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F and 33F), which represent 90% of all serotypes that cause invasive pneumococcal disease.[31] The vaccine is usually recommended for all elderly people and some at-risk groups, including those with chronic respiratory diseases.[29,31] The PPV induces a T-cell-independent immune response, eliciting serotype-specific antibodies that opsonize pneumococci of corresponding serotypes and promote the phagocytic activity of macrophages and polymorphonuclear leukocytes.[29,31] In general, among immunocompetent adults, the PPV induces a twofold or greater increase in serotype-specific antibody titers within 2–3 weeks of vaccination, although certain high-risk individuals (including COPD patients) may respond poorly.[29,31,41] Given that polysaccharide antigens do not induce a T-cell-dependent immune response, memory B cells are absent and this limits the period of vaccine protection. Prevaccination levels of antibody titers are generally reached within 5–10 years of the primary dose and an anamnestic response does not occur at revaccination, although there is a significant increase in antibody levels.[29,31,34,35]

Revaccination is recommended for those persons who received PPV23 below 65 years of age,[29,31] but its clinical effectiveness has not been clearly proven.[42] Unfortunately, the immunologic correlates of protection against both invasive and noninvasive pneumococcal disease are unknown.

Recently, Musher et al. reported that a new dose of PPV23 administered 10 years after a first or a second dose in older adults was generally well tolerated and immunogenic, inducing a similar postvaccination antibody level to the primary dose. The study concluded that immunogenicity is preserved after multiple PPV23 doses without evidence of a lower-than-expected immune response (i.e., without hyporesponsiveness).[43]

The nature of immune responses after PPV among patients with chronic respiratory diseases is uncertain. Several studies have reported that there is a similar antibody response in COPD patients as compared with the general population.[44] Others have observed a trend towards a poorer response,[45] and some have reported that many subjects with COPD respond poorly to some serotypes than younger healthy adults.[46,47] Some studies have also reported that the decrease in antibody titers appears to be more rapid in COPD patients.[45,48] Importantly, some studies have reported higher prevaccination antibody levels in COPD patients than in the general population,[45,49] probably due to frequent exposure of this population to pneumococcal infections during exacerbations, which could explain observations of a higher proportion of nonresponders in this population.[45] It seems that local or systemic corticosteroid therapy have no impact on antibody levels induced by vaccination.[47,49,50] Recently, a study has reported that working-age adults with asthma are also at increased risk of IPD[51] and, similar to COPD, greater prevaccination antibody levels in asthma patients than in control subjects have been observed.[52] This heterogeneity may be extremely important in explaining the sometimes very different results observed in different studies.

PPV has the potential to prevent disease and death from pneumococcal infections, but conflicting results have been reported and the degree of protection afforded against various clinical end points and within different populations remain controversial. More than ten meta-analyses on the efficacy of PPV in adults have been published during the past two decades,[53–64] including two specifically focused on COPD patients.[63,64] The large number of meta-analyses reflects the difficulties in reaching a clear conclusion, especially for at-risk populations. Generally, the meta-analyses differed by quality level qualification for the distinct trials, selection criteria used for including or excluding studies, statistical methods, grouping of subpopulations according to the presence of risk factors, or the location of the studies (developed or low-income countries). According to most of the meta-analyses, PPV is effective in preventing IPD, but its effectiveness in preventing noninvasive pneumococcal infections and other clinically relevant outcomes is not clear.

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