Characterization of Antibodies to Capsular Polysaccharide Antigens ofHaemophilus influenzaeType b andStreptococcus pneumoniaein Human Immune Globulin Intravenous Preparations

Abstract

The most common infections in primary immune deficiency disease (PIDD) patients involve encapsulated bacteria, mainly Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae (pneumococcus). Thus, it is important to know the titers of Hib-and pneumococcus-specific antibodies that are present in immune globulin (Ig) intravenous (IGIV) preparations used to treat PIDD. In this study, seven IGIV preparations were tested by enzyme-linked immunosorbent assay and opsonophagocytic activity for antibody titers to the capsular polysaccharides of Hib and five pneumococcal serotypes. Differences in Hib-and pneumococcus-specific antibody titer were observed among various IGIV preparations, with some products having higher-or lower-than-average titers. Opsonic activity also varied among preparations. As expected, IgG2 was the most active subclass of both binding and opsonic activity except against pneumococcal serotype 6B where IgG3 was the most active. This study determines antibody titers against capsular polysaccharides of Hib and pneumococcus in seven IGIV products that have been shown to be effective in reducing infections in PIDD patients. As donor antibody levels and manufacturing methods continue to change, it may prove useful from a regulatory point of view to reassess IGIV products periodically, to ensure that products maintain antibody levels that are important for the health of IGIV recipients.

Serotype-Specific and Age-Dependent Generation of Pneumococcal Polysaccharide-Specific Memory B-Cell and Antibody Responses to Immunization with a Pneumococcal Conjugate Vaccine

“…The responses of toddler B cells to the polysaccharides in the vaccine may be affected by the immunogenicity of the antigen. In immunized adults the polysaccharide of serotype 14 is more immunogenic than that of serotype 23F, and that of serotype 4 is poorly immunogenic (42). The data reported here show the opposite for toddlers, with the immunogenicity of serotype 4 followed by that of serotype 14 and then that of serotype 23F.…”

Streptococcus pneumoniae antibody titres in patients with primary antibody deficiency receiving intravenous immunoglobulin (IVIG) compared to subcutaneous immunoglobulin (SCIG)

“…In our study and in other reported studies, the most common Spn antibody levels noted to be decreased in the IVIG preparations were 4 and 9V, which are included among the serotypes causing the majority of disease in PIDD patients, along with serotypes 6B, 14 and 19F [14]. Clinically, we observed no serious bacterial infections in either IVIG-or SCIG-treated groups; however, despite the Spn antibody titre findings, patients treated with SCIG had significantly decreased infections compared to patients treated with IVIG, having similar Spn antibody concentrations.…”

“…Takahashi et al [13] compared five lots of four commercially available IVIG preparations in Japan and found comparatively low antibody titres to Spn serotypes 4, 7F and 9V, with none of the IVIG preparations containing the required Spn concentrations against serotypes 4 and 9V. Mikolajczyk et al [14] analysed five lots each of seven commercial IVIG preparations and found that antibody levels to Spn serotypes 14 and 19F were several-fold higher than those to types 4, 6B and 9V. The results of these various studies measuring antibody titres to Spn serotypes in patients receiving IgG replacement therapy, including ours, suggests that the variations in antibody concentrations may be due to different donor pools used in the preparation of IVIG products.…”

Selective subnormal IgG3 in 121 adult index patients with frequent or severe bacterial respiratory tract infections

“…Antibodies produced to the polysaccharide capsule are type-specific and protect against infections [23][24][25][26][27]. In one study, IgG1 in seven commercial intravenous IgG preparations contained nearly as much antipneumococcal antibody as IgG2 on a per-milligram-ofIgG-subclass basis [28]. Anti-pneumococcal polysaccharide antibodies of the IgG1 and IgG3 subclasses occur in persons who have IgA deficiency [29] or heavy chain constant region deletions of the 2 gene [30,31].…”