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

Streptococcus pneumoniae (S. pneumoniae) strains colonize the nasopharynx and can cause mucosal infections in the upper airway and middle ear, pneumonias, and invasive infections like bacteremia, sepsis, and meningitis. Over 90 serotypes, defined by the structure of their capsular polysaccharides, are known. Twenty‐three of these serotypes cause most infections and several of these serotypes can develop antibiotic resistance. Susceptibility factors that increase the susceptibility to S. pneumoniae mucosal and invasive infections include all forms of primary and secondary antibody deficiencies. Many patients affected by one of these deficiencies benefit from the regular administration of human gamma globulin (IgG) preparations. Donors of plasma units used to prepare human IgG have varying concentrations of IgG antibodies against relevant S. pneumoniae serotypes. These antibodies are developed in response to colonization and common subclinical infections and by routine vaccination with S. pneumoniae polysaccharide vaccines. The presence of an adequate concentration of these protective antibodies against all prevalent serotypes needs to be determined to assure the effectiveness of human IgG. All presently available methods to assess IgG antibodies against S. pneumoniae capsular polysaccharides have advantages and pitfalls that are analyzed in this review. In vitro testing does not provide a complete or necessarily accurate measurement of the effectiveness of antibodies in vivo. For regulatory purposes, caution needs to be used in the interpretation of currently available assays that measure pneumococcal antibody levels. Monitoring S. pneumoniae infections in patients treated with IgG and tracing information about IgG lots used to treat these patients should be encouraged.

Section: Pneumococcal Immunity In Human Gamma Globulinsupporting

confidence: 59%

Section: Pneumococcal Immunity In Human Gamma Globulinmentioning

confidence: 98%

Overview of antibody‐mediated immunity to S. pneumoniae: pneumococcal infections, pneumococcal immunity assessment, and recommendations for IG product evaluation

Sorensen

Edgar

2018

“…In general, there tends to be low lot‐to‐lot variability among lots of a product derived from an isolated geographic region . However, other studies have observed variability in antibody levels among lots of a manufacturer's product produced using the same methods but from different donor pools, and similar serotype‐specific trends in antibody levels among different manufacturers but from the same donor pool . Taken together, these findings suggest that the immune experience of a particular population influences the composition of the final product.…”

Section: Pneumococcal Antibodies In Immunoglobulin Productsmentioning

confidence: 99%

“…59,60 CONCLUSIONS Available evidence suggests that pneumococcal antibodies in immunoglobulin products can vary, largely due to different plasma donor pools or manufacturing processes, or both. 50,51,54 It is reasonable to measure pneumococcal antibodies as a means of monitoring such immunologic differences among products, since patients with PID often have pneumococcal infections, plasma donors have been vaccinated with pneumococcal vaccines, and pneumococcal antibody assays have been developed and extensively characterized during vaccine development. In addition, for the same reasons, measuring pneumococcal antibodies should be useful in the diagnosis and therapeutic monitoring of patients with PID.…”

Section: Studies Using Opamentioning

confidence: 99%

Measuring quantity and function of pneumococcal antibodies in immunoglobulin products

LaFon

Nahm

2018

BACKGROUND Immunoglobulin replacement therapy is a cornerstone of the treatment of primary immunodeficiencies. Preparations used for replacement therapy are processed by purifying immunoglobulins from large pools of plasma, which were obtained from healthy donors. The constituent antibodies in these products depend on the immune history of the donor pool as well as manufacturing processes that differ among manufacturers. For these reasons various methods have been proposed to examine the levels and function of antibodies to organisms such as Streptococcus pneumoniae, which frequently causes infections in patients with immunodeficiencies. Pneumococcal antibody levels or antibody function can be measured with enzyme‐linked immunosorbent assay (ELISA) or multiplexed opsonophagocytosis assay (MOPA). Although these assays were developed initially to assess the immunogenicity of pneumococcal vaccines, the techniques have been adapted to evaluate immunoglobulin products as well. STUDY DESIGN AND METHODS This article provides a concise review of the analytic techniques for measuring pneumococcal antibodies and prior studies of immunoglobulin products utilizing these methods. RESULTS Studies utilizing these assays have demonstrated that antibody levels of immunoglobulin products can vary with time, location, and manufacturer. CONCLUSIONS We highlight current issues and future considerations concerning measurement of pneumococcal antibodies in immunoglobulin products, and the assays used for this purpose.

“…Current immunization schedules include 12 vaccines, many of which contain antigens against multiple different viruses or serotypes of bacteria, 28 so that at least 40 different responses could be studied, but space allows review of selected examples only. Additional data on antibodies for which there are vaccines, including measles virus, 29 varicella-zoster virus, 30 tick-borne encephalitis virus, 31 and rabies lyssa virus 32 ; as well as data on titers in sera from immune-deficient patients receiving IgG replacement therapy, [33][34][35][36] and a comparison of antibody titers in IgG preparations and patient sera against bacteria for which vaccines are not available 37 are published elsewhere. Table 1 presents data on antibodies to bacterial antigens from several studies of multiple lots of products produced in the US, UK, and EU.…”

Section: Antibodies Against Common Bacterial Pathogens and Toxinsmentioning

confidence: 99%

Antibodies to vaccine antigens in pooled polyclonal human IgG products

Berger¹

2018

Immune‐deficient patients depend on the antibodies in pooled human immunoglobulin G (IgG) preparations to remain free from serious infections. The potency of IgG preparations is therefore an ongoing concern. The use of pooled IgG to prevent infection is based on the concept that healthy adults have recovered from infections earlier in life and maintain relatively high antibody titers. In general, vaccine‐induced immunity is less robust or long‐lasting than immunity after natural infection, and many infectious diseases which were formerly widely prevalent have become much less common due to improved hygiene and vaccines. This raises questions as to the adequacy of protective antibodies in current IgG preparations. This paper reviews available data on antibodies against selected bacterial and virus vaccine antigens in current IgG products. Most products contain sufficient antibody to yield levels above minimal protective concentrations to a broad range of pathogens and toxins. Illustrative examples of effects of vaccines on antibody content of IgG products are also discussed: antibody titers to hepatitis A virus in donor plasma pools in both the US and EU are dropping due to decreased natural infection, but they are still sufficient to provide robust protection. Increasing seroprevalence of hepatitis B virus as a result of immunization suggests that antibody titers against this virus may actually be increasing. Finally, serial studies suggest that pooled IgG provides protection against seasonal influenza viruses despite year‐to‐year antigenic drift, and is also likely to provide at least some protective antibody against potentially pandemic strains.