Measles Virus Neutralizing Antibodies in Intravenous Immunoglobulins: Is an Increase by Revaccination of Plasma Donors Possible?

Abstract

We report a screen of plasma donors confirming that widespread use of childhood measles vaccination since 1963 resulted in a decrease in average measles virus antibody titers among plasma donors, which is reflected in intravenous immunoglobulins (IVIGs). The measles virus antibody titer, however, is a potency requirement for IVIGs, as defined in a Food and Drug Administration regulation. To mitigate the decline in measles virus antibody titers in IVIGs and to ensure consistent product release, revaccination of plasma donors was investigated as a means to boost titers. However, revaccination-induced titer increases were only about 2-fold and short-lived.

Longitudinal changes in measles antibody titers in plasma donors and minimum antibody levels of immunoglobulin products for treatment of primary immunodeficiency

“…Measles antibody titers in donated plasma were measured by ELISA in 1169 individual donor samples obtained from 23 collection centers in the United States during August and September of 2017. Consistent with previous studies, plasma measles antibody titers were substantially higher in donors born before the introduction of the measles vaccine in 1963, compared with donors born after 1963 (Fig. ).…”

“…The results in Fig. are consistent with results obtained during similar snapshot studies conducted in 2007 and 2011 . For the 2007 study, measles antibody titers were analyzed in samples from 3320 donors collected on June 20, 2007.…”

“…In addition, the measles neutralizing antibody level is used to indicate that the activity of all antibodies has been maintained during the manufacturing process. Consistent with previous studies, we have observed strong declines in measles neutralizing antibody titers in plasma from donors born after the introduction of the measles vaccine in 1963. The likely explanation for this decline is that measles vaccination induces lower titers of measles neutralizing antibody than does natural measles infection .…”

Immunoglobulins and virus antibody titers: of past needs, current requirements, and future options

“…To mitigate the concerns around decreasing measles virus antibody titers, and thus potentially failing Ig lot release, measles (re‐)vaccination of plasma donors to boost antibody levels has recently been evaluated. However, this resulted in only an approximately twofold increase in antibody titers that returned to baseline within a few months after vaccination—clearly not a long‐term sustainable solution …”

Measles antibody trough levels after treatment with immunoglobulin products and predicted levels assuming lower measles antibody specifications

“…However, the plasma donor population is changing over time from persons with immunity to disease to persons with predominantly vaccine‐induced measles immunity. Vaccination produces lower levels of measles virus neutralizing antibodies compared to wild‐type infection, resulting in a decline in the measles antibody levels of IG products over time . This decline in measles virus neutralizing antibody levels prompted thorough review in 2007 by stakeholders including the Food and Drug Administration, patient groups, IG manufacturers, the Blood Products Advisory Committee, and the Plasma Protein Therapeutics Association .…”