Time Course of Antibody Response to Tetanus Toxoid and Pneumococcal Capsular Polysaccharides in Patients Infected With HIV

Abstract

The temporal course of the humoral immune response to T-cell-dependent and T-cell-independent type 2 antigens was evaluated in HIV-infected patients. In all, 26 seropositive patients were vaccinated with tetanus toxoid and 23-valent pneumococcal vaccines; total IgG and IgG1 antibodies to tetanus toxoid (Ttox) and total IgG and IgG2 antibodies against 23 Streptococcus pneumoniae capsular antigens (PPS) were measured at baseline, 2 months, and 12 months after vaccination. For the Ttox, baseline levels of IgG1 (Ttox-IgG1) increased from 11.0 to 19.5 mg/L at 2 months postimmunization. Overall only 6 patients (23%) showed a significant response. At 12 months postvaccination, Ttox-IgG and T-tox-IgG1 were significantly lower than baseline levels (Ttox IgG basal; 11.0 mg/L, 12 months; 0.8 mg/L, Ttox IgG1 baseline; 13.1 mg/L, Ttox IgG1 12 months; 2.4 mg/L) and in 10 patients, antibodies that fell below protective levels (0.6 mg/L). In contrast with PPS, a significant response was observed at 2 and 12 months (PPS-IgG basal; 35.9 U/ml, 2 months; 151.4 U/ml, 12 months; 59.7 U/ml; PPS-IgG2 baseline 20.3 U/ml, 2 months; 113.2 U/ml, 12 months; 51.9 U/ml). Overall, 19 patients (76%) showed an immune response to pneumococcal polysaccharides antigens. Immunization with the Ttox T-cell-dependent antigen fails to elicit a significant immune response and may induce inhibition of antibody production in HIV-infected patients. In contrast, immunization with a T-cell-independent type 2 antigen can cause the pneumococcal polysaccharides to induce significant immune response in a high proportion of HIV-infected patients.

Use and interpretation of diagnostic vaccination in primary immunodeficiency: A working group report of the Basic and Clinical Immunology Interest Section of the American Academy of Allergy, Asthma & Immunology

“…Current tetanus toxoid vaccines are immunogenic in all immunocompetent subjects, irrespective of age, with a protective humoral 5-year time span in 95% of the population, 160 whereas immunocompromised subjects, such as those who have undergone transplantation (solid organ or bone marrow), receive chemotherapy, or are infected with HIV, will demonstrate variable response to tetanus toxoid antigen, depending on the net state of immunosuppression. 161 In general, tetanus toxoid vaccines demonstrate no significant immunogenic variability because of the nature of the antigen and thus are good diagnostic tools for evaluation of immune competence to protein antigens. Thus an absent response should be considered abnormal until proved otherwise.…”

Vaccination in HIV-infected patients

“…Kroon et al [5] reported that only 83% of patients with CD4 count of less than 100 achieved a protective titer after tetanus immunization compared 100% of those with CD4 count of more than 100, and postvaccine geometric mean titer was correlated with CD4 count. Talesnik et al [35] found only 23% of patients from Chile mounted greater than a twofold rise in antibody titer after tetanus vaccination; at 12 months, geometric mean titer had fallen much lower than baseline. In contrast, Janoff et al [3] reported 80% to 100% of immunized HIV patients had tetanus-specific IgG above preimmunization levels at 6 months postvaccination.…”

“…Both tetanus and influenza vaccination have been associated with increased apoptosis in peripheral blood mononuclear cells [31,34]. This may explain the paradoxical results of an interesting Chilean study, in which predominantly asymptomatic HIV-infected adults not undergoing therapy showed initial short-term increases in antibody to tetanus after vaccination but had antibody levels well below baseline a year afterwards [35].…”

“…Studies of vaccine immunogenicity are difficult to compare and interpret because of the different serotypes tested in different studies and because early studies that did not preabsorb sera with cellwall polysaccharide may have inadvertently measured nonspecific cell-wall polysaccharide antibody instead of antibody to specific serotypes [8•]. Immunogenicity is not dependent on CD4 count [4,7,51], but recent HIV-seroconverters and patients with CD4 counts greater than 500 have essentially normal antibody responses [9,10], whereas those of most other HIV-infected patients are diminished [8•,35,52,53]. Antipneumococcal antibody wanes quickly, with levels falling to baseline within 1 year in both adult…”

Maternal and Neonatal Tetanus

“…With disease progression, immune response and serum tetanus antibody concentrations decrease. [105][106][107][108][109][110] This blunted response suggests that H IV-infected individuals might need more frequent booster doses. 106,107 Placental transfer of tetanus IgG was significantly lower in H IV-infected Brazilian mothers than in uninfected controls, 111 a finding that was not replicated in a subsequent study in Malawi.…”