Pneumococcal conjugate vaccine for adults: a new paradigm

Abstract

A 13-valent pneumococcal conjugate vaccine has been studied in adults aged ≥ 50 years to compare the immune response to that induced by the 23-valent pneumococcal polysaccharide vaccine, which has been the standard of care over the past 30 years. The results demonstrate that adults, regardless of whether they are naive or previously vaccinated with the polysaccharide vaccine, have an overall superior antibody response when vaccinated with the conjugate vaccine compared with the pneumococcal polysaccharide vaccine. More importantly, the nature of the response is indicative of a T-cell-dependent response that elicits immunological memory and, therefore, primes the immune system for either natural exposure or subsequent booster vaccination with either conjugate or polysaccharide vaccine. The conjugate vaccine, which has been successful in reducing pneumococcal disease in children, now provides a new approach to preventing pneumococcal disease, including community-acquired pneumonia, in adults.

Figure 1.

Design of a phase 3, randomized, modified double-blind, active-controlled, multicenter trial (Study 004) conducted in the United States in subjects naive to 23-valent pneumococcal polysaccharide vaccine (PPSV23). Subjects aged 60–64 years were randomized to receive either 13-valent pneumococcal conjugate vaccine (PCV13) or PPSV23 as a first dose; subjects aged 50–59 years received PCV13 only as a first dose. All groups received a second vaccination with either PCV13 or PPSV23, 3–4 years after the first dose. Opsonophagocytic activity was measured at the time of the first dose, 1 and 12 months after the first dose, at the time of the second dose, and 1 month after the second dose. Abbreviations: PCV13, 13-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine.

Figure 2.

Design of a phase 3, randomized, modified double-blind, active-controlled multicenter trial (Study 3005) conducted in the United States and Sweden in healthy subjects aged at least 70 years who received a previous vaccination with 23-valent pneumococcal polysaccharide vaccine (PPSV23) at least 5 years before study enrollment. Subjects were randomized to receive either 13-valent pneumococcal conjugate vaccine (PCV13) or PPSV23 as a first dose, with both groups receiving a dose of PCV13 1 year after the first dose. Opsonophagocytic activity was measured at the time of each dose and 1 month after each dose. Abbreviations: PCV13, 13-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine.

Figure 3.

Functional immune responses for pneumococcal serotype 1 (geometric mean titer) in the pivotal noninferiority trial (Study 004) measured pre- and postvaccination using a functional opsonophagocytic activity assay. Antibodies were determined before first vaccination (pre-dose 1), 1 month after vaccination (1 month post), and 12 months after first vaccination (12 months post); and before the second vaccination 3–4 years later (pre-dose 2) and 1 month after the second vaccination (post-dose 2). Abbreviations: GMT, geometric mean titer; OPA, opsonophagocytic activity; PCV13, 13-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine.

Figure 4.

Functional immune responses for pneumococcal serotype 1 (geometric mean titer) in the pivotal noninferiority trial (Study 3005) measured pre- and postvaccination using a functional opsonophagocytic activity assay. Antibodies were determined before first vaccination (pre-dose 1), 1 month after vaccination (post-dose 1), before the second vaccination (pre-dose 2), and 1 month after the second vaccination (post-dose 2). Abbreviations: GMT, geometric mean titer; OPA, opsonophagocytic activity; PCV13, 13-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine.