Streptococcus pneumoniae is a grampositive diplococcus, which asymptomatically colonizes the upper respiratory tract [1], but can also cause diseases like rhinosinusitis [2], pneumonia [3], otitis media [4] or meningitis [5]. In severe cases S. pneumoniae (or “Pneumococci” as they are also termed) can induce septic shock syndrome, a life-threatening event [6]. Thus, specific prophylaxis has been developed and vaccination against the most common strains of S. pneumoniae is recommended for children, patients over 51 years of age and populations at risk, e.g. patients receiving immunosuppression after organ transplantation or persons with immune defects [7, 8].
As more than 90 different serovars of S. pneumoniae could be identified so far [9], research aims at developing vaccines that deliver broad immunity. So far, four different vaccines have been licensed and are in clinical use: Prevnar® (Wyeth/Pfizer), Synflorix® (GlaxoSmithKline), Prevnar13® (Pfizer) and Pneumovax23® (Merck) [10, 11].
Prevnar® (or Prevenar®, as it is marketed in Austria) is a heptavalent conjugated polysaccharide vaccine consisting of polysaccharides from pneumococcal serotypes 4, 6B, 9 V, 14, 18C, 19F, and 23F, individually conjugated to CRM197, a non-toxic diphtheria toxin mutant [12]. Synflorix® covers the same serovars as Prevnar® plus serotypes 1, 5, and 7F. It is also a conjugated polysaccharide vaccine, using nonlipidated cell-surface liporotein (protein D) of Non-Typeable Haemophilus influenzae (NTHi) as well as tetanus and diphtheria toxoid as carriers [13]. Prevnar13® (Prevenar13® in Austria), also a conjugated polysaccharide vaccine (to CRM197), delivers immunity against serovars 1, 3, 4, 5, 6A, 7F, 9 V, 14, 18C, 19A, 19F, 23F [14].
Pneumovax23®, the non-conjugated, 23-valent vaccine, however, consists of polysaccharides from serovars 1, 2, 3, 4, 5, 6B, 7F, 8, 9 N, 9 V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F & 33F and covers theoretically 85–90% of all circulating strains [15].
In Austria, the recommended vaccination scheme for infants is a conjugated vaccine at months 3, 5 and 12. This early start of vaccination is advised as the peak of meningitis manifestations caused by S. pneumoniae is within the 2nd year of life. Moreover, people over 51 years of age are advised in Austria to undergo vaccination, too. This population is not primarily affected by invasive pneumococcal diseases (meningitis or sepsis), but at risk to develop severe pneumonia. Thus, the Austrian Ministry of Health recommends a two-step immunization procedure, starting with the conjugated polysaccharide vaccine Prevenar13® followed by Pneumovax23® after 8 weeks. This serial immunization regimen has been established due to the better initial response in antibody titres to Prevenar13®, which is effectively boostered by immunization with Pneumovax23®, but also extends immunity to the 11 serovars that are not covered by Prevenar13®. It is not fully clear yet, how long these protective effects last; therefore people in Austria are advised to refresh their immunization protection. Preliminary data suggest that the protection lasts at least 3.5 years [8].
In Austria, populations at extended risk, such as patients with immune defects, HIV-positive, organ-transplanted or splenectomized patients, but also persons with cochlea implants or liquor-fistulas are advised to receive vaccinations between the age of 18 and 50 as well, depending on their pre-immunization status with either a conjugated or the non-conjugated 23-valent vaccine [8]. When and to which extent booster injections are necessary is still under investigation.
However, even an optimal vaccination status cannot fully prevent pneumococcal disease as our case report demonstrates.