Functional Testing of Humoral Immunity in the Prevnar 20 Era

Humoral immune disorders such as common variable immunodeficiency and specific antibody deficiency are prevalent in clinical practice and require accurate functional testing of humoral immunity for diagnosis and to guide treatment approach. Traditionally, the 23-valent pneumococcal polysaccharide vaccine (PPSV23) has been used to assess polysaccharide antibody responses by measuring pre- and post-vaccination pneumococcal titers. However, the recent introduction of pneumococcal conjugate vaccines (PCVs), such as PCV13, PCV15, and PCV20, into the childhood and adult vaccine schedules has significantly reduced the number of unique serotypes available for testing and in turn has complicated the evaluation process. We retrospectively analyzed serotype-specific antibody responses in patients aged 2 to 65 years who received PPSV23 at the University of Virginia Health System to compare diagnostic outcomes using all 23 serotypes vs the limited number of unique serotypes not included in previous PCVs-11 serotypes for PCV13 recipients and 4 for PCV20 recipients. Our findings reveal that although previous PCVs mean that there is a reduced number of serotypes available for interpretation, PPSV23 testing maintains diagnostic accuracy between 81% and 84%. Despite limitations, the use of PPSV23 remains a valuable tool for identifying patients with clinically significant humoral immune deficiencies. In the future, alternative diagnostic approaches such as Salmonella typhi polysaccharide vaccine response and opsonophagocytosis assays may become more frequently used as part of the evaluation of humoral immune disorders.