Pneumococcal vaccination responses in adults with subnormal IgG subclass concentrations

Abstract

Background: We sought to compare Pneumovax®23 responses in adults with subnormal IgG subclass concentrations. We studied adults with normal total IgG, frequent/severe respiratory infection, and subnormal IgG1, IgG3, or IgG1 + IgG3 before and after Pneumovax®23. We defined response as serotype-specific IgG > 1.3 μg/mL and aggregate response as IgG > 1.3 μg/mL for ≥70% of all serotypes tested. We compared patients with and without serotype-specific responses and performed logistic regression on aggregate responses using: age; male sex; body mass index; autoimmune condition(s); atopy; other allergies; subnormal IgGSc immunophenotypes; IgA; and IgM. Results: There were 59 patients (mean age 44 ± 13 (SD) years; 83.1% women). Median days between pre-and post-Pneumovax®23 testing was 33 (range 19-158). The median post-vaccination summated concentration of serotypespecific IgG was higher in patients with subnormal IgG1 than subnormal IgG3 (responders and non-responders). All subnormal IgG1 + IgG3 non-responders responded to serotypes 8, 9 and 26, unlike other non-responders. Subnormal IgG3 responders had lower responses to serotypes 1, 4, 12, 23, 26, and 51. Subnormal IgG3 nonresponders had higher responses to serotypes 1, 3, 8, 9, 12, 14, 19, 51, and 56. Response rates decreased with increasing age. Aggregate responders were: subnormal IgG1, 54%; IgG3, 46%; and IgG1 + IgG3, 46%. Regression on aggregate response revealed lower response with male sex (odds ratio 0.09 [95% CI 0.01, 0.77]) and atopy (0.17 [0.03, 0.83]). Conclusions: Serotype-specific IgG responses to Pneumovax®23 were greater in patients with subnormal IgG1 than subnormal IgG3. Male sex and atopy were associated with lower aggregate responses.

Characterization of adult patients with IgG subclass deficiency and subnormal IgG2

“…pneumoniae serotypes before or after PPSV23 were common in adults with IgGSD and normal IgG2 levels [ 23 , 26 , 31 , 38 ]. In one study, serotype-specific IgG responses to Pneumovax®23 were greater in adults with IgGSD and subnormal IgG1 only than subnormal IgG3 only [ 40 ]. Some adults with frequent or severe respiratory tract infection due to encapsulated bacteria have suboptimal IgG2 responses to polysaccharide antigens [ 7 , 8 , 10 ].…”

“…We defined serotype-specific IgG levels as either protective (�1.3 mg/L) or non-protective (<1.3 mg/L) [39]. We defined aggregate pneumococcal polysaccharide response as S. pneumoniae serotype-specific IgG >1.3 μg/mL for �70% of serotypes in specimens obtained �28 d after PPSV23 [40].…”

“…We defined aggregate pneumococcal polysaccharide response as S . pneumoniae serotype-specific IgG >1.3 μg/mL for ≥70% of serotypes in specimens obtained ≥28 d after PPSV23 [ 40 ].…”

“…The fourth patient had 0/6 protective serotype-specific antibody levels pre-PPSV23 and 5/6 protective serotype-specific antibody levels post-PPSV23. Thus, three of these four patients with subnormal IgG2 had no aggregate IgG response to PPSV23 [40]. Data available for the remaining 14 patients were insufficient to determine aggregate PPSV23 response.…”

Specific Antibody Deficiency in Adult Patients With IgG or IgG Subclass Deficiency

“…Parker et al . 26 showed that in patients with subnormal IgG3 levels, non-responders had a reduced response to serotypes (1, 3, 8, 9, 12, 14, 19, 51 and 56). Furthermore, antibodies of the IgG3 subclass from several commercial intravenous IgG preparations had the most potent binding and opsonic activity for pneumococcal serotype 6B, which is associated with mortality in invasive pneumococcal diseases.…”