Comparison of an opsonophagocytic assay and IgG ELISA to assess responses to pneumococcal polysaccharide and pneumococcal conjugate vaccines in children and young adults with sickle cell disease

Children with sickle cell disease were immunized with either 2 doses of 7-valent pneumococcal conjugate vaccine followed by 1 dose of 23-valent pneumococcal polysaccharide vaccine or a single dose of 23-valent vaccine. Functional antibodies to 7 vaccine serotypes were measured by a flow cytometric opsonophagocytic assay (OPA) and compared with IgG anticapsular polysaccharide antibody concentrations measured by ELISA. Moderate correlations were found between OPA and ELISA antibody titers for all 7 serotypes (r values, 0.41-0.70; P<.001 for all serotypes). After immunization with 23-valent vaccine, geometric mean antibody titers by OPA were significantly higher in the combined schedule group for 5 of 7 vaccine serotypes but were significantly higher for only 2 of 7 serotypes as measured by ELISA. The ability of OPA to show a greater differential response to the 2 immunization schedules used in this study suggests that it may be useful in the evaluation of immunization regimens involving pneumococcal conjugate vaccines.     

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 (0.5 ml) of PCV7. In addition, 149 RA patients receiving corresponding treatments and 47 healthy controls were vaccinated with a single dose (0.5 ml) of PPV23. Serotype-specific IgG to 23F and 6B were measured at vaccination and 4–6 weeks 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.     

A randomized, double-blind trial of pneumococcal vaccination in adult allogeneic stem cell transplant donors and recipients.

BACKGROUND: Adult allogeneic hematopoietic stem cell transplant (HSCT) recipients are at high risk of invasive pneumococcal disease but have suboptimal responses to the recommended pneumococcal polysaccharide vaccine (PPV23). Pneumococcal conjugate vaccine (PCV7) may improve immunogenicity in this population, and a donor vaccination strategy may benefit patients undergoing HSCT. METHODS: Sixty-four pairs of donors and recipients scheduled to undergo HSCT were randomized to receive either PPV23 or PCV7. Vaccinations were administered to donors before transplantation and to recipients at 6 months after transplantation. Serotype-specific antipneumococcal titers were measured in donors at the time of harvest and in recipients before transplantation and 6 and 12 months after transplantation. RESULTS: Overall, immunogenicity was poor with both strategies. However, at 6 months, response to at least 1 serotype was seen in 0 (0%) of 19 and 8 (38.6%) of 21 evaluable recipients whose donors had received PPV23 and PCV7, respectively (P=.003). At 12 months, response was seen in 10 (55.6%) of 18 and 20 (90.9%) of 22 HSCT recipients who had received PPV23 and PCV7, respectively (P=.02). Multivariate logistic regression revealed that, at 12 months after transplantation, the type of vaccine given was the only significant factor affecting response, with an odds ratio of 8.85 (95% confidence interval, 1.62-47.6; P=.012) favoring PCV7. CONCLUSION: A donor and recipient paired vaccination strategy with PCV7 demonstrated safety and greater immunogenicity than did a similar strategy with PPV23.     

Donor immunization with pneumococcal conjugate vaccine and early protective antibody responses following allogeneic hematopoietic cell transplantation

Patients undergoing hematopoietic cell transplantation (HCT) are at increased risk for infections with Streptococcus pneumoniae and have long-lasting, impaired antibody responses to pneumococcal polysaccharide vaccines. We examined whether donor immunization with a heptavalent pneumococcal conjugate vaccine (PCV7) would elicit protective antibody responses to additional doses of vaccine administered early after transplantation. Ninety-six patients scheduled to receive an allogeneic hematopoietic cell transplant were randomized with their donors to receive either a dose of PCV7 vaccine or no vaccine before transplantation. All patients received PCV7 at 3 months, 6 months, and 12 months following transplantation, and serotype-specific antibody concentrations were determined after each dose. Following HCT, geometric mean antibody concentrations of patients in the immunized donor group were significantly higher for 5 of the 7 vaccine serotypes after one dose (P <.05) and for 4 of the 7 serotypes after 2 doses of vaccine (P <.03). Sixty-seven percent of patients in the immunized donor group had presumed protective IgG concentrations more than or equal to 0.50 microg/mL to all 7 serotypes following the first dose of vaccine compared to 36% in the unimmunized donor group (P =.05). After the third dose of vaccine, both groups had more than 60% of patients with concentrations at least 0.50 microg/mL to all vaccine serotypes. Donor immunization enhances early antibody responses of patients undergoing HCT to pneumococcal conjugate vaccine. A 3-dose schedule of PCV7 vaccine at 3, 6, and 12 months is immunogenic in these patients regardless of donor immunization.     

Long-term Comparative Immunogenicity of Protein Conjugate and Free Polysaccharide Pneumococcal Vaccines in Chronic Obstructive Pulmonary Disease

Background.?Although the 23-valent pneumococcal polysaccharide vaccine (PPSV23) protects against invasive disease in young healthy persons, randomized controlled trials in chronic obstructive pulmonary disease (COPD) have demonstrated no benefit in the intention-to-treat population. We previously reported that the 7-valent diphtheria-conjugated pneumococcal polysaccharide vaccine (PCV7) is safe and induced greater serotype-specific immunoglobulin G (IgG) and functional antibody than did PPSV23 1 month after vaccination. We hypothesized that these advantages would persist at 1 and 2 years. Methods.?One hundred eighty-one patients with moderate to severe COPD were randomized to receive PPSV23 (n?=?90) or PCV7 (1.0?mL; n?=?91). We measured IgG by enzyme-linked immunosorbent assay and assessed functional antibody activity by a standardized opsonophagocytosis assay, reported as a killing index (OPK). We determined differences in IgG and OPK between vaccine groups at 1 and 2 years. Results.?Relative to PPSV23, PCV7 induced greater OPK at both 1 and 2 years for 6 of 7 serotypes (not 19F). This response was statistically greater for 5 of 7 serotypes at 1 year and 4 of 7 at 2 years. Comparable differences in IgG were observed but were less often statistically significant. Despite meeting Centers for Disease Control and Prevention criteria for PPSV23 administration, almost 50% of individuals had never been vaccinated. No differences in the frequency of acute exacerbations, pneumonia, or hospitalization were observed. Conclusions.?PCV7 induces a greater functional antibody response than PPSV23 in patients with COPD that persists for 2 years after vaccination. This superior functional response supports testing of conjugate vaccination in studies examining clinical end points. Clinical Trials Registration: NCT00457977.     

Kinetics of antibody concentration and avidity for the assessment of immune response to pneumococcal vaccine among children with bone marrow transplants

The kinetics of the immune response to the 23-valent pneumococcal polysaccharide vaccine (PPV) were studied in 38 children who received bone marrow transplants (BMTs). Anti-pneumococcal antibody concentrations increased 1 and 3 months after vaccination for all 5 serotypes tested, but, in 21 children, the vaccine was not adequately immunogenic. Children vaccinated <18 months after receiving a BMT had a 4.2-fold increased odds of poor response (P=. 06). Antibody concentrations returned close to baseline levels 9 months after vaccination. Avidity declined significantly as early as 1 month after vaccination and remained low thereafter. Antibody concentration responses to PPV were superior among 9 healthy control children (P=.001); 37 of 38 children with a BMT elicited adequate, persistent immune responses to Haemophilus influenzae conjugate vaccine. Immune responses to PPV in children with a BMT are suboptimal, short lived, and associated with declining avidity. The different kinetics of antibody concentration and avidity indicate that both markers should be used for evaluating pneumococcal vaccines in this high-risk population.     

Incidence of invasive pneumococcal disease among elderly people in Southern Catalonia, Spain, 2002-2009: an increase in serotypes not contained in the heptavalent conjugate vaccine

Population-based surveillance study conducted among persons ≥ 65 years old in Southern Catalonia, Spain during 2002-2009. All cases with isolation of pneumococcus from normally sterile bodily fluids were included. Incidence rates of invasive pneumococcal disease (IPD) as well as rates of infections caused by serotypes included in the heptavalent pneumococcal conjugate vaccine (PCV7) and the 23-valent polysaccharide pneumococcal vaccine (PPV23) were compared for early (2002-2005) and contemporary (2006-2009) periods. Mean incidence rate (per 100,000 population-year) of IPD across study period was 48.0 [95% CI (confidence interval): 30.1-72.5]. Incidence rates for PCV7 serotypes slightly decreased by 21% between 2002-2005 and 2006-2009 (from 9.2 to 7.3; p = 0.511) whereas rates of IPD due to nonPCV7 serotypes largely increased by 172% (from 15.6 to 42.4; p < 0.001) during the same period. For PPV23 but nonPCV7 types, incidence rates increased by 146% (from 10.9 to 26.9; p < 0.001) whereas rates for nonPPV23 serotypes increased by 237% (from 4.6 to 15.5; p = 0.001). As an overall effect of these changes, the incidence of all IPD increased by a significant 69% (95% CI: 29%-110%). Specific incidence rates of serotypes 6A (from 1.7 to 4.1; p = 0.182), 7F (from 1.7 to 5.7; p = 0.052) and 19A (from 0.6 to 6.2; p = 0.004) substantially increased between both periods. According to these findings, Southern Catalonia region can be classified as a mesoendemic area of pneumococcal infections among elderly people, with a recent increase incidence of some nonPCV7 serotypes (especially 19A).     

Primary and booster salivary antibody responses to a 7-valent pneumococcal conjugate vaccine in infants

Salivary anticapsular antibody responses to a 7-valent pneumococcal conjugate vaccine (7VPnC) were measured in healthy infants. Infants received diphtheria-tetanus-pertussis/Haemophilus influenzae type b (DTP/Hib; group 1), DTP/Hib and 7VPnC (group 2), or DTP and 7VPnC/Hib (group 3) at ages 2, 3 and 4 months. All children received 23-valent pneumococcal polysaccharide vaccine at age 13 months. Salivary IgA and IgG responses to primary immunizations were generally poor. IgA mean concentrations at age 5 months were higher in the treatment groups than in control subjects for serotype 14 only (P<.001). At age 13-14 months, there were marked increases in IgA (mean fold difference, 3.7-4.9) and IgG (mean fold difference, 4. 1-11.7) levels for serotypes 4, 9V, 14, and 19F and serotypes 4, 18C, 19F, and 23F, respectively, in the treatment groups. This contrasts with low IgA (1.2 and 1.4) and IgG (1.3 and 2.2) mean fold differences for non-7VPnC serotypes 1 and 5. The results suggest that 7VPnC primes for mucosal memory responses in infants.     

Functional antibodies elicited by an 11-valent diphtheria-tetanus toxoid-conjugated pneumococcal vaccine

The aluminium-adjuvanted 11-valent pneumococcal conjugate vaccine containing polysaccharides 1, 4, 5, 7F, 9V, 19F, and 23F (coupled to tetanus protein) and polysaccharides 3, 6B, 14, and 18C (coupled to diphtheria toxoid) elicits high antibody concentrations in Filipino infants when given at ages 6, 10, and 14 weeks and 9 months simultaneously with the national vaccination program. We evaluated functional activity of these antibodies by using a viable cell opsonophagocytic assay (OPA). The OPA titers correlated (r=0.53-0.74) with the respective antibody concentrations. The geometric mean OPA titers after 3 vaccine doses were 276.9 (serotype 4), 12.3 (serotype 6B), 46.0 (serotype 14), 119.3 (serotype 19F), and 206.3 (serotype 23F). The functionality of antibodies increased after the fourth dose of vaccine (i.e., the concentration required for in vitro killing of pneumococci decreased). Both the quantity and quality of antibodies are important in the evaluation of immunogenicity of pneumococcal vaccines.     

Routine Pneumococcal Vaccination of Children Provokes New Patterns of Serotypes Causing Invasive Pneumococcal Disease in Adults and Children

IntroductionRoutine vaccination of infants with protein-conjugated 7-valent pneumococcal vaccine (PCV7) begun in 2000 initiated a sea change of prevalent serotypes (STs) in invasive pneumococcal disease (IPD). The authors investigated in 1 community all STs causing IPD during 5 years before (PRE) and 2, 5-year periods after (POST1 and POST2) its initiation and found that PCV7 adversely affected ST coverage of 23-valent pneumococcal polysaccharide vaccine (PPV23) among adults.MethodsFrom 1996–2010, 620 consecutive Streptococcus pneumoniae IPD strains from adults (521) and children (99) hospitalized with IPD in Huntington, WV, were collected. Each strain was typed by Quellung reaction. The Marshall University Institutional Review Board approved this study.ResultsBy 6 to 10 years after the initiation of PCV7, IPD in children decreased significantly, whereas IPD in adults increased significantly. In both adults and children, IPD due to PCV7 STs decreased significantly. In adults with IPD, PCV7 STs were replaced by several non-PCV7 STs including STs contained in PPV23 but not in PCV7 and STs not contained in either vaccine. IPD due to 4 nonsusceptible STs included in PCV7 decreased from PRE to POST1 and POST2. IPD due to nonsusceptible STs not included in PCV7 increased from PRE to POST1 and POST2.ConclusionsRoutine PCV7 decreased IPD in children but not in adults. Predominant STs changed—children exhibited fewer PCV7 STs and adults exhibited fewer PCV7 and PPV23 STs—reducing vaccine coverage and increasing the risk of replacement STs causing IPD in adults.     

Emerging pneumococcal carriage serotypes in a high-risk population receiving universal 7-valent pneumococcal conjugate vaccine and 23-valent polysaccharide vaccine since 2001

Background  

In Australia in June 2001, a unique pneumococcal vaccine schedule commenced for Indigenous infants; seven-valent pneumococcal conjugate vaccine (7PCV) given at 2, 4, and 6 months of age and 23-valent pneumococcal polysaccharide vaccine (23PPV) at 18 months of age. This study presents carriage serotypes following this schedule.     

Emergence of invasive pneumococcal disease caused by nonvaccine serotypes in the era of 7-valent conjugate vaccine.

BACKGROUND: Little is known about the epidemiology of invasive pneumococcal disease (IPD) after the introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in Spain and other European countries. METHODS: We performed a 10-year prospective study including all children with culture-proven IPD admitted to Sant Joan de Deu Hospital, a children's center in the southern area of Barcelona, Catalonia, Spain. PCV7 was introduced in June 2001, and the current estimate of PCV7 coverage is 45%-50%. RESULTS: Comparing the prevaccine period (1997-2001) with the vaccine period (2002-2006), among children aged <2 years, the rate of IPD increased from 32.4 episodes per 100,000 population to 51.3 episodes per 100,000 population (an increase of 58%; 95% confidence interval, 2%-145%), and among children aged 2-4 years, the rate increased from 11.3 episodes per 100,000 population to 26.5 episodes per 100,000 population (an increase of 135%; 95% confidence interval, 31%-320%). At clinical presentation, the rate of pneumonia and/or empyema among children aged <5 years increased from 3.6 episodes per 100,000 population to 15.1 episodes per 100,000 population (an increase of 320%; 95% confidence interval, 98%-790%). These increased rates of IPD were caused by non-PCV7 serotypes, which represented 38% and 72% of infecting serotypes in the prevaccine and vaccine periods, respectively (P=.001). Penicillin resistance decreased from 48% in the prevaccine period to 27% in the vaccine period (P=.005). In the vaccine period, there was an emergence of previously established virulent clones of non-PCV7 serotypes 1 and 5. There was also an increase in the prevalence of serotypes 19A and 6A expressed with different clonal types, including Spain(23F)-1 and Spain(6B)-2. CONCLUSIONS: Since the introduction of PCV7 for children, there has been an emergence of IPD caused by virulent clones of non-PCV7 serotypes that has been associated with significant clinical changes and a decrease in antibiotic resistance.     

Immunogenicity of sequential pneumococcal vaccination in subjects splenectomised for hereditary spherocytosis

Splenectomy predisposes for invasive pneumococcal disease. We investigated the immune response of splenectomised hereditary spherocytosis (HS) patients upon sequential pneumococcal vaccination. Thirty-nine HS-patients (2- to 18-year-old) had undergone near-total or total splenectomy. All received one dose of 7-valent pneumococcal conjugate vaccine (PCV-7) and 23-valent-pneumococcal-polysaccharide vaccine (PPV-23) 2 months apart. Pneumococcal antibodies against serotypes 5/6B/7/14/18C/19F/23F and immunoglobulin serum concentrations were determined before PCV-7 and 4 weeks after PPV-23. Significant rises in antibody geometric mean concentrations were observed after PCV-7 except for serotypes 5 and 7, which increased after PPV-23. We found no impact of the mode of splenectomy.     

Incidence of pneumococcal disease due to non-pneumococcal conjugate vaccine (PCV7) serotypes in the United States during the era of widespread PCV7 vaccination, 1998-2004

BACKGROUND: Widespread use of pneumococcal conjugate vaccine (PCV7) resulted in decreases in invasive disease among children and elderly persons. The benefits may be offset by increases in disease due to serotypes not included in the vaccine (hereafter, "nonvaccine serotypes"). We evaluated the effect of PCV7 on incidence of disease due to nonvaccine serotypes. METHODS: Cases of invasive disease were identified in 8 geographic areas through the Centers for Disease Control and Prevention's Active Bacterial Core surveillance. Serotyping and susceptibility testing of isolates were performed. We calculated the incidence of disease for children aged <5 years and adults aged > or =65 years. We compared rates of serotype-specific disease before and after PCV7 was licensed for use. RESULTS: The annual incidence of disease due to nonvaccine serotypes increased from an average of 16.3 cases/100,000 population during prevaccine years (1998-1999) to 19.9 cases/100,000 population in 2004 for children aged <5 years (P=.01) and from 27.0 cases/100,000 population during prevaccine years to 29.8 cases/100,000 population in 2004 for adults aged > or =65 years (P=.05). Significant increases in the incidences of disease due to serotypes 3, 15, 19A, 22F, and 33F were observed among children during this period (P<.05 for each serotype); serotype 19A has become the predominant cause of invasive disease in children. The incidence of disease due to these serotypes also increased among elderly persons. CONCLUSIONS: The incidence of pneumococcal disease caused by nonvaccine serotypes is increasing. Ongoing surveillance is needed to monitor the magnitude of disease caused by nonvaccine serotypes, to ensure that future vaccines target the appropriate serotypes.     

Burden of invasive pneumococcal disease and serotype distribution among Streptococcus pneumoniae isolates in young children in Europe: impact of the 7-valent pneumococcal conjugate vaccine and considerations for future conjugate vaccines

ObjectivesThe overall reported burden of invasive pneumococcal disease (IPD) varies among countries in Europe. This review describes the epidemiology and serotype distribution of IPD in European children from studies published from 1990 to 2008.MethodsAverages were derived from all studies from all countries that had available data.ResultsBefore widespread immunization with 7-valent pneumococcal conjugate vaccine (PCV7), the overall mean annual incidence of IPD in children aged <2 years was 44.4/100 000. The mean case fatality rate for IPD was 3.5%, and resistant rates were approximately 23% for penicillin G (minimum inhibitory concentration ≥2 mg/l), 41% for erythromycin, and 9% (≤5 years) for third-generation cephalosporins. The most common serotypes causing IPD were 14, 6B, 19F, and 23F, all of which are included in PCV7. Vaccine serotype coverage ranged from 37% to 100% for PCV7, with mean increases in coverage of 7% and 16% for investigational 10- and 13-valent pneumococcal conjugate vaccines, respectively. The most common IPD isolates since PCV7 introduction in Belgium, France, Germany, Greece, Norway, Portugal, Spain, and the UK were serotypes 1, 19A, 3, 6A, and 7F.ConclusionsWith routine effective use of PCV7, a general decline in IPD, antibiotic non-susceptibility, and vaccine serotypes has been observed. The most common IPD isolates since PCV7 introduction are serotypes 1, 19A, 3, 6A, and 7F, highlighting the need for inclusion of these serotypes in future vaccine formulations.     

Immunogenicity of a combined schedule of 7‐valent pneumococcal conjugate vaccine followed by a 23‐valent polysaccharide vaccine in adult recipients of heart or lung transplants

R. Gattringer, H. Winkler, S. Roedler, P. Jaksch, H. Herkner, H. Burgmann. Immunogenicity of a combined schedule of 7‐valent pneumococcal conjugate vaccine followed by a 23‐valent polysaccharide vaccine in adult recipients of heart or lung transplants.
Transpl Infect Dis 2011: 13: 540–544. All rights reserved Abstract: A combined schedule of 7‐valent pneumococcal conjugate vaccine (PCV7) followed by 23‐valent pneumococcal polysaccharide vaccine (PPV23) was evaluated retrospectively in 26 adult recipients of heart or lung transplants. PCV7 was immunogenic in these patients but there appeared to be no benefit from the additional PPV23 dose.     

Pneumococcal polysaccharide revaccination: immunoglobulin g seroconversion,persistence, and safety in frail,chronically ill older subjects

OBJECTIVES: To determine the 1-month postpneumococcal polysaccharide-revaccination immunoglobulin G (IgG) antibody response, its persistence at 1 year, and tolerability of revaccination in frail, chronically ill older nursing facility residents. DESIGN: Prospective study conducted between December 1998 and July 2000. SETTING: Six skilled nursing facilities in the Minneapolis-St. Paul, Minnesota, metropolitan area. PARTICIPANTS: Sixty-seven subjects aged 65 and older having received primary vaccination with pneumococcal polysaccharide vaccine (PPV) at least 5 years before enrollment. INTERVENTION: Revaccination with one dose of 23-valent PPV. MEASUREMENTS: Adverse events and concentrations of seven individual pneumococcal polysaccharide type-specific IgG antibodies (against serotypes 4, 6B, 9V, 14, 18C, 19F, 23F) and their aggregate before and 1 and 12 months after revaccination. RESULTS: A significant increase in all individual and aggregate median antibody concentrations over baseline was observed 1 month after revaccination. However, after 1 year, the increase remained significant only for serotypes 6B and 18C and the aggregate parameter. One month after revaccination, the mean increase in antibody concentration over baseline was significantly greater than 1.4-fold for six of the seven serotypes and the aggregate. However, the increase was not significantly greater than 1.4 at 1 year for any of the serotypes or the aggregate. Minor, self-limited localized adverse reactions and systemic reactions occurred in 11.3% of the subjects. CONCLUSIONS: In frail, chronically ill older nursing facility residents, revaccination with 23-valent PPV at least 5 years after primary vaccination (whether primary vaccination occurred before or after age 65) is associated with a significant, albeit brief, immunological response for most of the serotypes tested. Revaccination was well tolerated.     

A case-control study to investigate serological correlates of clinical failure of 23-valent pneumococcal polysaccharide vaccine in HIV-1-infected Ugandan adults

We have investigated the association between the concentration of anti-polysaccharide pneumococcal capsule-specific (anti-PS) immunoglobulin G and the killing activity, in serum, in invasive pneumococcal disease (IPD) events and response to 23-valent polysaccharide vaccine in human immunodeficiency virus (HIV)-infected Ugandans. Case patients with IPD had lower concentrations of anti-PS IgG before and after vaccination and before the IPD event (P<.01 for 5 [i.e., 4, 9V, 14, 18C, and 19F] of 6 serotypes assessed). After vaccination, case patients were less likely than were control subjects to develop detectable serum killing activity against the 2 serotypes tested--for 19F, this activity was detected in 16% of case patients versus 37% of control subjects (P=.08); for 23F, it was detected in 11% of case patients versus 40% of control subjects (P=.02). Thus, absolute concentration of anti-PS IgG and an attenuated response to polysaccharide are associated with risk of IPD in HIV-infected adults.     

Immunity to cross-reactive serotypes induced by pneumococcal conjugate vaccines in infants.

Infants were immunized with 1 of the 3 experimental pneumococcal conjugate vaccines that contain 6B and 19F but not 6A or 19A serotypes. Their sera were studied for the capacity to opsonize Streptococcus pneumoniae 6A, 6B, 19A, and 19F serotypes and the level of IgG antibody to the 4 serotypes. Significant increases were observed in the number of infants with detectable opsonophagocytic titers with 3 conjugate vaccines for 6B (vaccine) serotype but with only 2 vaccines for 6A (cross-reactive) serotype. Significant increases were observed with 2 conjugate vaccines for 19F serotype but with only 1 vaccine for 19A serotype. Thus, some conjugate vaccines may elicit cross-protection better than others. In addition, correlations between opsonophagocytic titers and IgG antibody levels by ELISA were high for 6B and 19F serotypes but low for 6A and 19A serotypes. Thus, ELISA may be an inadequate surrogate assay of vaccine response for cross-reactive serotypes.     

Reduction in functional antibody activity against Streptococcus pneumoniae in vaccinated elderly individuals highly correlates with decreased IgG antibody avidity.

The pneumococcal polysaccharide vaccine is recommended as a means of preventing invasive disease in the elderly. We compared responses to the 23-valent polysaccharide vaccine in 46 previously unvaccinated, healthy, institutionalized elderly persons (mean age, 85.5 years) with those in 12 healthy younger adults (mean age, 37 years) by measuring prevaccination and postvaccination serum IgG antibody concentrations (by ELISA), functional antibody activity (by opsonophagocytosis), IgG antibody avidity, and passive protection in mice. Postvaccination IgG antibody concentrations for two serotypes (6B and 19F) of the five studied (4, 6B, 14, 19F, and 23F) were significantly lower in elderly than in younger adults; however, opsonophagocytic activity was significantly reduced for all serotypes in the elderly. Sera with reduced opsonophagocytic activity (titer, <64) correlated with low IgG antibody avidity and protected mice poorly against pneumococcal challenge. In elderly persons receiving polysaccharide vaccination, there was a significant reduction in the functionality of postvaccination antibodies, and this appeared to increase with advanced age.