International Journal of Antimicrobial Agents 32 (2008) 199–206 Review Pneumococcal vaccines: mechanism of action, impact on epidemiology and adaption of the species Mathias W. Pletz a,∗ , Ulrich Maus a , Norbert Krug b , Tobias Welte a , Hartmut Lode c a Department of Pulmonary Medicine, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany b Division of Immunology, Allergology and Airway Research, Fraunhofer Institute of Toxicology and Experimental Medicine, Nikolai-Fuchs-Straße 1, 30625 Hannover, Germany c RCMS–Institute for Clinical Pharmacology, Charit´ e-University Medicine Berlin, Hohenzollerndamm 2, 10717 Berlin, Germany Abstract Pneumococcal infections elicited by Streptococcus pneumoniae (pneumococcus) (pneumonia, otitis media, sinusitis, meningitis) are fre- quently occurring diseases that are associated with considerable morbidity and mortality even in developed countries. Pneumococci colonise the nasopharynx of up to 50% of children, and up to 5% of adults are pneumococcal carriers. Two pneumococcal vaccines are currently in clinical use. One of them contains 23 capsular polysaccharides of the as yet known 91 different pneumococcal serotypes. Because polysaccha- ride vaccines primarily induce a B-cell-dependent immune response, this type of vaccine prevents bacteraemia but does not efficiently protect the host against pneumococcal infection. In 2000, a vaccination programme was launched in the USA making use of a novel pneumococcal conjugate vaccine containing capsular polysaccharides derived from the seven most frequent pneumococcal serotypes causing pneumococcal disease in children <2 years of age. Conjugation of capsular polysaccharides with a highly immunogenic protein, i.e. a non-toxic diphtheria toxoid, induces a B- and T-cell response resulting in mucosal immunity and thus effectively protects against vaccine serotypes that induce invasive pneumococcal disease, thereby at the same time reducing vaccine serotype carrier rates. Pronounced herd immunity resulted in a decrease in invasive pneumococcal diseases in vaccinees and non-vaccinees as well as reduced antibiotic resistance rates. However, recent studies report that serotypes eradicated by the vaccine are being replaced by non-vaccine pneumococcal serotypes. This so-called ‘replacement’ might soon threaten the success of vaccine use. © 2008 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. Keywords: Streptococcus pneumoniae; Vaccine; Conjugated; Antibiotics; Resistance; Epidemiology 1. Introduction Although pneumococcal diseases are frequent and vaccine development was started early, the development of an effica- cious vaccine was not successful for a long time. The main reason is the low immunogenicity of polysaccharides, which are the target of opsonising antibodies. Two types of vac- cines are currently in clinical use: polysaccharide vaccines; and pneumococcal conjugate vaccines. Polysaccharide vaccines have been available since the mid 1980s. These vaccines contain purified capsular polysaccha- rides from 23 pneumococcal serotypes (1, 2, 3, 4, 5, 6b, 7F, 8, ∗ Corresponding author. Tel.: +49 511 532 3661; fax: +49 511 532 3533. E-mail address: Pletz.Mathias@mh-hannover.de (M.W. Pletz). 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F and 33F). Polysaccharides primarily induce a B-cell- dependent immune response via release of immunoglobulin M (IgM) [1]. Such polysaccharide vaccines are not recom- mended for use in children <2 years of age, probably due to their immature immune system. Vaccination of adults with polysaccharide vaccines requires re-vaccination after 5–6 years [2]. However, non-responders to immunisation are especially frequent in older patients [3]. It has also been observed that antibodies against bacterial capsular polysac- charides are difficult to induce in response to non-conjugated polysaccharide vaccines for corresponding meningococcal and Haemophilus vaccines [4,5]. The heptavalent pneumococcal conjugated vaccine (PCV-7) contains capsular polysaccharides from those 0924-8579/$ – see front matter © 2008 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. doi:10.1016/j.ijantimicag.2008.01.021