Pneumococcal Vaccine In Patients Research Articles

Heptavalent pneumococcal conjugate vaccine elicits similar antibody response as standard 23-valent polysaccharide vaccine in adult patients with RA treated with immunomodulating drugs

The objectives of the study were to compare antibody response in immunosuppressed patients with rheumatoid arthritis (RA) after vaccination with heptavalent pneumococcal conjugate vaccine (PCV7) to that of RA patients and healthy controls vaccinated with 23-valent polysaccharide vaccine (PPV23) and to study the impact of disease and/or treatment characteristics and type of vaccine on antibody response following pneumococcal vaccination in patients with RA. In total, 253 RA patients treated with methotrexate (MTX), anti-TNF blockers as monotherapy or anti-TNF + MTX were vaccinated with a single dose (0.5ml) of PCV7. In addition, 149 RA patients receiving corresponding treatments and 47 healthy controls were vaccinated with a single dose (0.5ml) of PPV23. Serotype-specific IgG to 23F and 6B were measured at vaccination and 4-6weeks after vaccination using ELISA. Antibody response ratio (ARR), i.e. ratio between post-/prevaccination antibody levels, was compared between corresponding treatment groups. Differences in ARR were analysed using analysis of variance. Positive antibody response (posAR) was defined as equal to or greater than twofold increase in prevaccination antibody levels. Possible predictors of posAR were analysed using logistic regression model. Corresponding RA treatment groups showed similar ARR and posAR for both serotypes regardless of vaccine type. Higher age at vaccination and concomitant MTX were identified as predictors of impaired posAR for both serotypes tested, whereas type of vaccine did not influence posAR significantly. PCV7 elicits similar antibody response as PPV23 in patients with RA receiving immunosuppressive treatment. In RA patients, higher age and MTX treatment but not type of vaccine predicted impaired posAR.

Effects of immunosuppression on immune response to pneumococcal vaccine in inflammatory bowel disease: A prospective study*

Since immunomodulators and antitumor necrosis factor (TNF) agents are increasingly used to treat inflammatory bowel disease (IBD), it is recommended to administer antipneumococcal vaccination to prevent opportunistic pneumonia. There is some evidence that concomitant immunosuppression may impair the immune response to vaccination. We aimed to evaluate the response rates to pneumococcal vaccination in four different treatment groups (mesalamine, azathioprine, infliximab, infliximab plus azathioprine). In all, 96 patients with IBD (54 with Crohn's disease; 42 with ulcerative colitis) were administered a 23-valent polysaccharide pneumococcal vaccine (PSV-23). The levels of antipneumococcal antibodies were measured prior to and at least 3 weeks after vaccination. Response rates and risk factors for impaired immunosuppression were investigated. Patients on mesalamine were used as a control group. Patients administered infliximab or the combination immunosuppressive therapy had significantly lower response rates to vaccination (57.6% and 62.5%, respectively) compared with the group on mesalamine (88.6%; P < 0.05 for both comparisons). Azathioprine alone did not influence the response rate to vaccination (78.9%; P = 0.43 vs. mesalamine group). Mean antibody titers after vaccination were significantly lower in patients under infliximab or combined immunosuppression than controls (P < 0.05). Immunosuppression with infliximab or combination therapy significantly decreased the likelihood of responding to vaccination (odds ratio [OR] = 0.17, 95% confidence interval [CI] 0.04-0.64, P = 0.009, and OR = 0.21, 95% CI 0.05-0.91, P = 0.038, respectively). Pneumococcal vaccination was generally safe and well tolerated. Anti-TNF therapy alone or in combination with azathioprine impairs the response to pneumococcal vaccination in patients with IBD. All patients with IBD should therefore be vaccinated before starting anti-TNF therapy.

Comparison of clinical features, antimicrobial susceptibility, serotype distribution and outcomes of patients with hospital- and community-associated invasive pneumococcal disease

Hospital-associated invasive pneumococcal disease (HA-IPD) is infrequently reported. A retrospective surveillance of IPD in a medical centre in Taiwan was conducted from 2000 to 2008 to compare the clinical and microbiological characteristics of HA-IPD and community-associated IPD (CA-IPD). HA-IPD was identified in 37 patients, comprising 12.3% of the 302 hospitalised patients with IPD. Patients with HA-IPD were more likely to have solid-organ cancer (40.5% vs. 16.6%; P = 0.001) or to have received immunosuppressive therapy (56.8% vs. 26.8%; P < 0.001). The 30-day mortality rate of HA-IPD was significantly higher than that of CA-IPD (40.5% vs. 16.2%; P = 0.001). Age ≥65 years [odds ratio (OR) = 2.10; P = 0.033], HA-IPD (OR = 2.90; P = 0.009) and liver cirrhosis (OR = 3.19; P = 0.009) were independent predictors of 30-day mortality. No significant differences in serotype distribution or in susceptible rates to penicillin (18.2% vs. 32.6%; P = 0.14) and cefotaxime (60.6% vs. 67.8%; P = 0.53) were found between HA-IPD and CA-IPD isolates. Similar prevalences of the serotypes included in the pneumococcal vaccines were found in isolates from patients with HA-IPD and CA-IPD. Among patients with HA-IPD and CA-IPD, 26 (78.8%) and 172 (73.2%) ( P = 0.45) had isolates of serotypes included in the 7-valent pneumococcal conjugate vaccine, and 30 (90.9%) and 224 (95.3%) ( P = 0.96) had isolates of serotypes included in the 23-valent pneumococcal polysaccharide vaccine, respectively. In summary, this study found that HA-IPD and CA-IPD were not significantly different with regard to serotype distribution and antimicrobial susceptibility in Taiwan. Patients with HA-IPD have a higher mortality rate, and pneumococcal vaccination for patients at increased risk for HA-IPD should be encouraged.

Safety and immunogenicity of pneumococcal vaccination in patients with rheumatoid arthritis during the treatments using biological agents

Safety and immunogenicity of pneumococcal vaccination in patients with rheumatoid arthritis during the treatments using biological agents

Immunosuppression Impairs Response to Pneumococcal Polysaccharide Vaccination in Patients With Inflammatory Bowel Disease

The treatment of inflammatory bowel disease (IBD) often includes immunosuppressive medications, which may increase the risk of vaccine-preventable illnesses. We aimed to assess the impact of immunosuppression on immune responses to pneumococcal vaccination in patients with IBD. The study design consists of a prospective controlled clinical trial. This study was carried out at a tertiary-care IBD clinic. The subjects for the study belonged to one of the following three groups: adult patients with IBD on combination TNF-blockers and immunomodulators (Group A), those without immunosuppressive therapy (Group B), and age-matched healthy controls (Group C). The treatment consisted of immunization with 23-valent pneumococcal polysaccharide vaccines (PSVs). The main outcome was immune response for five serotypes defined as a twofold or greater increase from pre-vaccination titers and > or =1 microg post-vaccination titer. Sixty-four subjects participated in the study: 20 in Group A, 25 in Group B, and 19 in Group C. Pre-vaccination titers were similar among the three groups. Vaccine responses were lower in Group A than in Group B (P< or =0.01 for four out of five antigens) and Group C (P<0.01 for all five antigens). Overall vaccine response was seen in 45, 80, and 85% of Groups A, B, and C (P=0.01), respectively. Immune response to PSV-23 is impaired in Crohn's disease (CD) patients on combination immunosuppressive therapy but is normal among non-immunosuppressed patients. Given the unpredictable likelihood for immunosuppressive therapy, newly diagnosed patients with IBD should undergo vaccination before the initiation of immunosuppressive therapy.

Vacunación frente al Streptococcus pneumoniae en sujetos portadores de un trasplante de órgano sólido

The risk of developing invasive pneumococcal disease in transplant patients is estimated at 28 to 36 per 1000 patients/year according to the type of organ transplanted. This rate is much higher than the estimated incidence in the general population. This study reviews the current experience regarding the different types of vaccinations against Streptococcus pneumoniae in transplant patients, the immunogenic response to pneumococcal vaccine in these patients, the clinical experience to date with the use of pneumococcal vaccines, and the utility of a sequential vaccination regime including the heptavalent vaccine and vaccine for the 23 serogroups. The immunogenicity produced by pneumococcal vaccines in transplant patients is lower and not as long-lasting as in immunocompetent individuals, and the revaccination regimen inducing the most favorable immunological response is unknown. Nonetheless, pneumococcal vaccination provides clear benefits to transplant recipients and should be given before transplantation whenever possible.

Effects of pneumococcal vaccine in patients with chronic respiratory disease

In developed countries, it is very difficult to demonstrate the effectiveness of pneumococcal vaccines because the incidence of pneumococcal pneumonia is very low.Vaccination against pneumococci infection was advised for 1378 outpatients, over 60 years of age, with chronic respiratory disease for more than one year. Of these patients, those who responded affirmatively to the advice were vaccinated against pneumococci between August and November 2002. The effectiveness of vaccination was evaluated by means of a 2-year cohort-study, comparing the vaccinated group (647) with the non-vaccinated group (731). The variables analyzed were the frequency of onset of bacterial respiratory infection, hospitalization due to bacterial respiratory infection and onset of pneumococcal respiratory infection.The incidence of bacterial respiratory infection and the incidence of pneumococcal respiratory infection to have decreased in the following 2 years (17.4%, 0.9%), as compared to the previous year (25.9%, 3.1%), in the vaccinated group. Conversely, the frequency was higher in the following 2 years (14.4%, 0.9%) as compared to the previous year (14.2%, 0.4%) in the non-vaccinated group. This inter-group difference was statistically significant. Simultaneous vaccination against pneumococci and influenza virus also resulted in a significant reduction in the incidence of bacterial respiratory infection. No decrease was observed in the frequency of hospitalization.These results indicate that pneumococcal vaccine is useful for elderly patients with chronic respiratory disease and that its efficacy may be enhanced by simultaneous vaccination against influenza.

Antibody response to 7-valent conjugated pneumococcal vaccine in patients with chronic lymphocytic leukaemia

Chronic lymphocytic leukaemia (CLL) is a common adulthood mature B-cell neoplasm. Infections are the most important cause of mortality in this condition, and Streptococcus pneumoniae has been considered the most important single pathogen. We investigated the immunogenicity of 7-valent pneumococcal conjugate vaccine in patients with CLL. The study material comprised 52 patients with CLL and 25 age- and sex-matched controls. The subjects were vaccinated with Prevenar pneumococcal conjugate vaccine. Serum samples were taken for antibody determinations before and four weeks after vaccination. Antibody response rates to vaccine antigens were lower in patients with CLL compared to controls. However, if the vaccine had been administered at an early stage of the disease, i.e. before commencement of chemotherapy and the development of hypogammaglobulinaemia, a significant vaccination response to at least six antigens was obtained in almost 40% of the CLL patients. Our results indicate that early administration of conjugate vaccine may be beneficial in CLL.

Determinants of influenza and pneumococcal vaccination in patients with chronic lung diseases

Despite strong recommendations, immunization rates for influenza and pneumococci are low. We aimed to analyse the vaccination status and its determinants in patients with chronic lung diseases. Information about actual influenza (IV) and pneumococcal (PV) vaccination status was obtained by a standardised questionnaire from 2491 patients presenting to a specialised centre of respiratory medicine in Rotenburg/Wuemme (Germany). Bivariate and multivariate analyses were used to identify potential determinants of IV and PV. Of 2131 patients with asthma and/or COPD, included into detailed analyses (52.0% male, mean age 56.6 years), 46.5% had received an IV and 14.6% a PV. Main reason for not being vaccinated was the lack of information, reaching 87.6% for PV (53.5% for IV); 37.0% saw no reason for an IV (PV 21.3%). Vaccination rates differed depending on the patients' age and education level. The results indicate a marked information deficit on immunization which is explicitly higher for PV. Target-group-specific strategies should increase the knowledge on vaccinations in order to avoid the development or aggravation of acute and chronic lung diseases.

Immune Response to Influenza Vaccine in Pediatric Patients With Inflammatory Bowel Disease

The aim of this study was to compare response to inactivated influenza vaccine in healthy children and pediatric patients with inflammatory bowel disease (IBD). A prospective, open-label, controlled clinical trial during influenza seasons of 2002-2004 was performed. Single-dose inactive trivalent influenza vaccine was administered. Immune response to vaccination was measured by pre-immunization and postimmunization hemagglutinin inhibition titers. A postimmunization hemagglutinin inhibition titer of 40 or higher was considered protective against influenza. IBD activity and adverse events were recorded. Eighty subjects were enrolled (29 healthy controls, 51 IBD patients). One patient did not complete the study. Patients were divided into 3 subgroups: infliximab and immunomodulatory (16), immunomodulatory (20), and anti-inflammatory therapy (14). Immunomodulatory therapy included corticosteroids, 6-mercaptopurine, or methotrexate. Overall, there was a statistically significant decrease in immune response in patients compared with healthy controls who received 1 influenza vaccine antigen (B/Hong Kong, P = .0125). Patients receiving infliximab and immunomodulatory therapy were less likely to respond to 2 influenza vaccine antigens (A/New Caledonia/20/99 and B/Hong Kong/330/2001, P = .018 and .0002, respectively). Fifteen subjects (19%) reported 19 mild adverse events: 11 (14%) reported soreness at the site, 4 (5%) reported having a cold, 3 (4%) reported flu-like symptoms, and 1 (1%) reported a headache. The clinical activity of IBD was not affected by vaccination. The serologic conversion rate to influenza vaccine in patients with IBD ranged from 33% to 85%. Patients on concomitant infliximab and immunomodulatory therapy are at risk of inadequate response to vaccination. The vaccine was safe and did not affect IBD activity.

Overcoming Barriers to Pneumococcal Vaccination in Patients With Pneumonia

Inpatient pneumococcal vaccination remains underutilized, and little data exist to guide hospital personnel in improving their performance. The authors report their experience with a stepwise program to improve vaccination assessment rates for hospitalized patients with community-acquired pneumonia. They assessed barriers to vaccination and applied a stepwise educational and intranet-based decision support implementation program for hospitalized patients with community-acquired pneumonia. Preintervention vaccination rates were 0%. Primary nursing and physician barriers were assessed. An educational intervention increased vaccination assessment rates to 35%, a nursing decision-support tool to 42%, and approval of a standing order policy to 96%. For patients older than 65 years, vaccination assessment rates increased 33%, 67%, and 100%, respectively. An educational program combined with a decision support tool and a standing order policy can improve vaccination assessment rates to high levels. This study suggests that a multidimensional intervention is required to improve compliance with inpatient vaccination best clinical practices.

Pneumokokken-Schutzimpfung bei obstruktiven Lungenerkrankungen - Was können wir erwarten?

Many countries' guidelines recommend pneumococcal vaccination for patients suffering from obstructive airway disease. This paper reviews the literature as to immunogenicity and safety of this immunization. There is no evidence for a negative effect of pneumococcal vaccination on these patients. Only a few data exist on the preventive impact of pneumococcal vaccination as to exacerbations of obstructive airway diseases. Existing studies mostly took up this question as a side aspect. The effect in children and adults appears limited. On the other hand, the pneumococcal conjugate vaccine prevents life-threatening invasive infections in children younger than 5 years, and pneumococcal polysaccharide vaccine protects healthy adults against bacteriaemic pneumonia. Thus, pneumococcal vaccination of patients suffering from obstructive airway disease is recommendable.

Pneumococcal vaccination of patients with systemic lupus erythematosus: Effects on generation of autoantibodies

Objectives: To assess the effect of vaccination against streptococcus pneumoniae on the generation of autoantibodies in patients with SLE.Materials and Methods: Twenty-four consecutive patients with SLE were vaccinated against streptococcus pneumoniae. Assessment was performed the day of vaccination and 2 months later and included evaluation of disease activity using the SLEDAI, serum levels of ESR, CRP, C3 and C4. The sera of the patients were tested by ELISA for anti-dsDNA, anticardiolipin (IgG and IgM), anti-Sm, anti-nRNP, anti-Ro/SSA, and anti-La/SSB.Results: The mean age at enrollment into the study was 39, mean disease duration 6.9 years. The SLEDAI score (mean ± SD) was 4.41 ± 2.92 at the time of vaccination and 4.47 ± 3.11, 2 months apart. At the time of vaccination, 10 patients had anti-dsDNA, 2 patients had anti-Sm, 5 had anti-nRNP, and 9 had anti-Ro/SSA, 4 had anti-La/SSB, 4 had anticardiolipin IgG and IgM. Two months after vaccination, no change was observed in the proportion of patients with anti-Sm, anti-dsDNA, anti-RNP, anti-Ro/SSA and anticardiolipin IgM. A single patient developed anticardiolipin IgG and another one turned anti-RNP negative.Conclusions: Vaccination against streptococcus pneumoniae did not trigger the generation of autoantibodies and confirms the clinical safety of this vaccine in SLE patients.

Antibody Production Deficiency With Normal IgG Levels in Bronchiectasis of Unknown Etiology

No defined cause of bronchiectasis is currently found in approximately 50% of cases. Bronchiectasis is a common long-term complication in patients with primary hypogammaglobulinemia. To ascertain whether antibody production deficiency with normal total serum IgG levels is associated with bronchiectasis. Antibody response to a pneumococcal unconjugate vaccine and an Haemophilus influenzae type b conjugate vaccine was prospectively studied in all consecutive adult patients with bronchiectasis of unknown etiology who were assessed in our chest outpatient clinic from January 1994 to October 2001. Serum-specific antibodies were measured by enzyme-linked immunosorbent assay, and the results were compared with those obtained in a healthy adult control group. Antibody production deficiency was defined as a failure to respond to either vaccine. One hundred seven patients were included in the study (mean age, 46.3 years). Antibody production deficiency was diagnosed in 12 patients (11%). A significantly higher incidence of otitis media, lower serum IgG2 subclass levels, and lower preimmunization antibody levels to Streptococcus pneumoniae and H influenzae type b were observed in patients with antibody production deficiency. The probability of antibody production deficiency in patients with a history of otitis media was 20%, 26% in those with low IgG2 subclass levels, and 58% in those with both a history of otitis media and low IgG2 subclass levels. Antibody production deficiency with normal IgG levels may be associated with bronchiectasis, making it advisable to evaluate the antibody response to both the H influenzae and pneumococcal vaccines in patients with bronchiectasis of unknown etiology, particularly in those with a history of otitis media, low IgG2 subclass levels, and low levels of baseline specific antibodies.

The Effect of tumor necrosis factor blockade on the response to pneumococcal vaccination in patients with rheumatoid arthritis and ankylosing spondylitis

Objective To assess the effect of anti-tumor necrosis factor (TNF) α therapies on the immunogenicity of pneumococcal vaccination in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Methods A group of 16 consecutive patients (11 with RA and 5 with AS) treated either with infliximab or etanercept, and a control group of 17 age-matched RA patients treated with disease-modifying medications other than anti-TNF-α, received intradeltoid injection with 0.5 mL of pneumococcal vaccine. Pneumococcal polysaccharide (PPS)-specific IgG to 7 vaccine PPS (representing high- and low-prevalence serotypes) was measured by enzyme-linked immunosorbent assay in sera obtained before and 1 month after pneumococcal immunization. Results One month after vaccination, both groups had significant increases in the geometric mean concentration of capsule PPS-specific antibody and in the mean fold increase in antibody levels to all 7 serotypes, compared with prevaccination levels. However, compared with the control group, the TNF-α blockade-treated patients tended to have lower antibody increases for all the serotypes tested except serotype 14. In addition, lower proportions of TNF-α blockade-treated patients responded to pneumococcal vaccination compared with patients on other therapies. Similarly, more TNF-α blockade-treated patients were poor responders compared with patients not on anti-TNF-α treatment. Conclusion Treatment of groups of patients with etanercept or infliximab does not impair their mean antibody responses to pneumococcal vaccination. However, a larger proportion of RA patients may not respond adequately to pneumococcal vaccination once on TNF-α blockade therapies. Consequently, pneumococcal vaccination before starting TNF-α blockade therapy is recommended.

Immunogenicity and safety of pneumococcal vaccination in patients with rheumatoid arthritis or systemic lupus erythematosus.

Prevention of bacterial infection, which is a leading cause of morbidity in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), is a priority. However, the safety and immunogenicity of the pneumococcal vaccine in such patients remain controversial. We evaluated the currently available pneumococcal vaccine in patients with RA or SLE. Pneumococcal vaccination was not associated with an appreciable deterioration in any clinical or laboratory measure of disease activity in either group. One month after vaccination, patients in both groups had significant increases in geometric mean concentrations of pneumococcal polysaccharide-specific IgG to all 7 serotypes tested, as did control subjects. However, 14 (33.3%) of 42 patients with RA and 5 (20.8%) of 24 patients with SLE responded either to none or to only 1 of the 7 polysaccharides. Pneumococcal vaccination is generally safe and immunogenic in patients with RA or SLE, but a subset of patients may remain unprotected by the currently available vaccine.

Specific Antibody Response Against the 23-Valent Pneumococcal Vaccine in Patients With α1-Antitrypsin Deficiency With and Without Bronchiectasis

To assess the specific antibody response against polyvalent pneumococcal vaccine in patients with alpha(1)-antitrypsin deficiency (AATD) and respiratory infections. We investigated specific IgG, IgG1, and IgG2 antibody responses against the 23-valent antipneumococcal vaccine in 18 patients with AATD phenotype PiZZ, 9 of whom had bronchiectasis and 4 a history of recurrent pneumonia, and compared them with a control group of 40 healthy volunteers. Blood samples were drawn just prior to and 3 weeks after immunization. Quantification of specific IgG and its subclasses was performed by an enzyme-linked immunosorbent assay. For patients with AATD, mean increases in specific antipneumococcal titers were 4.7-fold (25 to 75% quartiles, 2.5- to 6.8-fold) for total IgG, 3.2-fold (1.2- to 4.9-fold) for IgG1, and 2.1-fold (1.8- to 3.7-fold) for IgG2. For the control group, the values were 3.3-fold (1.8- to 5.8-fold) for total IgG, 2. 5-fold (1.9- to 3.4-fold) for IgG1, and 3.1-fold (1.9- to 4.5-fold) for IgG2; differences were not significant. Patients with bronchiectasis showed a tendency toward higher levels of IgG subclasses than both control subjects and patients without bronchiectasis; however, there was a tendency toward lower postvaccination serum levels of specific antipneumococcal IgG, IgG1, and IgG2 in patients with bronchiectasis compared with patients without bronchiectasis, but this trend did not reach statistical significance. Three of the four patients with recurrent pneumonia did not show an appropriate IgG2 response. These results suggest that, as a group, patients with AATD have a preserved antibody response against pneumococcal polysaccharides. Patients with bronchiectasis show a tendency toward a decreased antibody response, even with increased serum levels of most Ig types. Individuals with an impaired IgG2 response seem to be at increased risk of recurrent pneumonia. Considering the pernicious effect of pulmonary infections on these patients and the preserved antibody response in a majority of them, pneumococcal vaccination should be recommended to patients with AATD.

Severe exacerbation of systemic lupus erythematosus after hepatitis B vaccination and importance of pneumococcal vaccination in patients with autosplenectomy: Comment on the article by Battafarano et al

Severe exacerbation of systemic lupus erythematosus after hepatitis B vaccination and importance of pneumococcal vaccination in patients with autosplenectomy: Comment on the article by Battafarano et al

Rapid loss of specific antibodies after pneumococcal vaccination in patients with human immunodeficiency virus-1 infection.

Pneumococcal infections are frequently observed in patients with human immunodeficiency virus (HIV) infection and active immunization has been recommended as prophylaxis in this patient group. We studied 103 out-patients with asymptomatic or mildly symptomatic HIV infection with respect to specific IgG and IgG2 pneumococcal antibodies before and after vaccination with a 23-valent pneumococcal polysaccharide vaccine. A significant increase ( > 2-fold) in IgG and IgG2 antibody levels was observed after 1 month in 69/103 patients (67%) with no correlation with the CD4 cell count at the time of vaccination. The response rate was not influenced by concurrent treatment with anti-retroviral monotherapy, or by age or gender. After immunization a strong correlation between IgG and IgG2 anti-pneumococcal antibodies was demonstrated. Nevertheless, 12 months after vaccination the specific antibody titres were not significantly different from pre-vaccination values. In conclusion, antibodies induced by pneumococcal vaccination in patients with HIV infection have a short duration. This raises the question as to whether vaccination will have any impact on clinical end-point in this group of patients.

Immunoglobulin isotype-specific antibody responses to pneumococcal polysaccharide vaccine in patients with recurrent bacterial respiratory tract infections.

Anti-pneumococcal IgM, IgG1, IgG2, and IgA antibody titers were determined in 61 pediatric patients with recurrent bacterial respiratory tract infections. The patients were divided in those with normal serum Ig levels (group 1, n = 46) and patients with dysimmunoglobulinemia (group II, n = 15). antibody titers to five pneumococcal serotypes (3, 4, 6A, 9N, and 19F) of different immunogenicity were determined by ELISA, before and 14 d after immunization with pneumococcal polysaccharide vaccine. In the patients of group I, IgM responses did not vary between the various serotypes. IgG1 antibodies reached high levels for pneumococcal types 3, 4, and 9N compared with an adult reference hyperimmune plasma pool, but remained low for the weak immunogenic types 6A and 19F. IgG2 antibody titers remained low and were nearly absent in 20/46 patients. The fold increase in IgA was high, but the ultimate IgA antibody levels remained low. IgA levels remained low to absent in 10/46 patients. Two patients (4%) of group I failed to show antipneumococcal antibodies of all Ig isotypes. In group II, 6/15 patients (40%) made no anti-pneumococcal antibodies of any isotype, whereas the remaining patients made no IgG2 and/or IgA anti-pneumococcal antibodies. We conclude that the frequency of nonresponders to pneumococcal vaccination in patients with normal serum Ig is low (4%). However, low IgG2 anti-pneumococcal levels are found in approximately 50% of the patients. In patients with dysimmunoglobulinemia, IgA and IgG2 responses were absent in virtually all patients, whereas 40% made no anti-pneumococcal antibodies of any isotype.