This study has shown that a substantial proportion of patients with a diagnosis of CVID are able to generate serum bactericidal antibodies following vaccination with plain meningococcal polysaccharide vaccine and that protective bactericidal antibody titers will persist for at least 1 year in the majority of responding patients.
In the study by Goldacker et al., a positive vaccination response was detected with 23% of CVID patients against polypeptide vaccines and with 18% against polysaccharide antigens (18
). The study by Ko et al. also suggested that some CVID patients could also respond to certain polysaccharide vaccines (21
). While almost all previous reports evaluated the quantity of antibody responses to certain vaccines, particularly pneumococcal polysaccharide vaccine, we used the SBA assay, an antibody-mediated complement-dependent method, to evaluate the function of antibody responses to meningococcal polysaccharide vaccine (7
). The presence of bactericidal activity by SBA assay indicates production of specific antibodies, and the rise in SBA titer is correlated with protection (23
). The patients were subclassified into three groups based on short and long-lasting responses to meningococcal polysaccharide vaccine.
Considering the results of this study and also other recent reports (18
), it is apparent that some patients with CVID can generate antibodies against protein or polysaccharide antigens. This observation is of practical importance for two reasons. First, it may help us to define clinical subgroups within this heterogeneous disease (18
). Second, it shows us that vaccination against encapsulated bacteria, such as Streptococcus pneumoniae
, Haemophilus influenzae
, and Neisseria meningitidis
, is worthwhile for some CVID patients and probably should be recommended for routine care.
The plain meningococcal polysaccharide vaccine induces a T-cell-independent immune response, which stimulates B cells to produce specific antibodies against the capsular polysaccharides. These antibodies have an important role in defense against bacterial infections by opsonization of bacteria for phagocytosis by macrophages and for classical complement-mediated killing (10
). However, as the polysaccharide cannot induce antibody avidity maturation or isotype switching, this polysaccharide vaccine generates relatively poor immunological memory for long-term protection (8
). This is reflected in the significant fold decreases of SBAs that we observed with both groups of CVID patients and controls. Thus, while responses could decay over time in some cases, repeat vaccination could have some benefits, especially in the transient responder group. However, the immunological basis of long-term protection is still poorly understood (7
) and further studies are needed to evaluate how CVID patients respond to repeat vaccination.
Comparison of some characteristics among the groups showed that bronchiectasis was significantly more common in groups I and II with poor vaccine response either 3 weeks after or 1 year after vaccination, while splenomegaly was a prominent finding for group I. It should be noted that discriminating between the complications that are part of the underlying immune dysregulation (such as splenomegaly) and those that are due to infections (such as bronchiectasis) is important (11
). Recurrent respiratory infections can lead to long-term complications such as bronchiectasis, which was detected with half of our patients. Poor antibody response to polysaccharide antigens could explain the development of bronchiectasis in the nonresponder group, while normal antibody responses to polysaccharide antigens could protect patients from recurrent severe pneumonia and consequently bronchiectasis (31
). A high rate of bronchiectasis in CVID patients with a paucity of switched memory B cells and poor antibody responses to polysaccharide vaccine have previously been shown (9
). Although low numbers of IgM memory B cells and an absence of IgM antibodies against polysaccharide antigens could underlie the recurrent pneumonia in this group of CVID patients (9
), it has not been confirmed in a pediatric population (31
). Splenomegaly also seems to be more common in the group of patients with low numbers of switched memory B cells (27
Although the study was performed on a group of patients who were under immunoglobulin replacement therapy, the fact that all patients who had a <4-fold rise in SBA titer from prevaccination to 3 weeks after vaccination remained nonresponders 1 year after vaccination implies that immunoglobulin infusions did not confound the measurements of SBA. There are also some complexities regarding antibody responses in CVID, which warrant discussion. Although quantitative and qualitative assessment of a panel of antibodies could be done, it is not clear how many antigens should be tested and which conclusion could be drawn in the case of normal response to some antigens and defective response to others (31
). The strength of our study is that it has used the widely accepted functional parameter of bactericidal activity and clinically relevant protective response.
In conclusion, this study has shown that some CVID patients can produce protective bactericidal antibody titers even 1 year after vaccination, similar to those of the normal population. Therefore, vaccination of CVID patients with certain vaccines should be strongly considered by clinical teams, while evaluation of antibody response could also show the T-cell-independent immune response of these patients. The responder patients, either transient or long term, may have a better prognosis than nonresponders.