Antibodies to vaccine antigens in pooled polyclonal human IgG products

Abstract

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.

Assuring immune globulin potency in a world of changing pathogen challenges

“…It was generally agreed that an opsonophagocytosis assay or a multiplex version of the opsonophagocytosis assay were most attractive, as they provide antibody functionality, are reproducible, and may be relatively stable over time. H. influenzae titers (by ELISA) were also stable across IG products in one study …”

“…Workshop participants identified potential candidates based on ability to cause disease in patients with PI. These were mostly respiratory pathogens, and included Streptococcus pneumoniae , Haemophilus influenzae , Moraxella catarrhalis , respiratory syncytial virus, parainfluenza, influenza, adenovirus, mycoplasma, and rhinovirus . Nonrespiratory pathogens discussed included cytomegalovirus, herpes simplex virus, enteroviruses, and meningococcus.…”

“…These were mostly respiratory pathogens, and included Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, respiratory syncytial virus, parainfluenza, influenza, adenovirus, mycoplasma, and rhinovirus. 14,28,29 Nonrespiratory pathogens discussed included cytomegalovirus, herpes simplex virus, enteroviruses, and meningococcus. Relatively limited data are available on the viral respiratory infection epidemiology of patients with PI in part because diagnostic cultures are not routinely performed.…”

“…H. influenzae titers (by ELISA) were also stable across IG products in one study. 28 Preliminary studies of neutralizing antibodies in IG to viral pathogens were also discussed. Titers against human adenovirus 5, respiratory syncytial virus, and parainfluenza 3 across IG lots in the United States showed relatively low lot-to-lot variation.…”

Antimicrobials

“…This may be specific for an organism, for example, V-ZIg (varicella-zoster immunoglobulin antibodies), or be pooled antibodies from a large number of people, in which case it will provide antibodies against a large number of organisms, but at a lower level. It is important to note that as with antimicrobial prophylaxis and unlike active immunisation this does not provide long-term protection (Berger 2018).…”