Pneumococcal Capsular Polysaccharide Vaccine Research Articles

A Novel Pneumococcal Surface Protein K of Nonencapsulated Streptococcus pneumoniae Promotes Transmission among Littermates in an Infant Mouse Model with Influenza A Virus Coinfection.

We established an infant mouse model for colonization and transmission by nonencapsulated Streptococcus pneumoniae (NESp) strains to gain important information about its virulence among children. Invasive pneumococcal diseases have decreased dramatically since the worldwide introduction of pneumococcal capsular polysaccharide vaccines. Increasing prevalence of nonvaccine serotypes, including NESp, has been highlighted as a challenge in treatment strategy, but the virulence of NESp is not well understood. Protective strategies against NESp colonization and transmission between children require particularly urgent evaluation. NESp lacks capsules, a major virulence factor of pneumococci, but can cause a variety of infections in children and older people. PspK, a specific surface protein of NESp, is a key factor in establishing nasal colonization. In our infant mouse model for colonization and transmission by NESp strains, NESp could establish stable nasal colonization at the same level as encapsulated serotype 6A in infant mice and could be transmitted between littermates. Transmission was promoted by NESp surface virulence factor PspK and influenza virus coinfection. However, PspK deletion mutants lost the ability to colonize and transmit to new hosts. Promotion of NESp transmission by influenza was due to increased susceptibility of the new hosts. PspK was a key factor not only in establishment of nasal colonization but also in transmission to new hosts. PspK may be targeted as a new candidate vaccine for NESp infection in children.

Evaluation of effectiveness, safety and cost-benefit of the 23– valent pneumococcal capsular polysaccharide vaccine for HIV-Infected patients

IntroductionDue to the lack of understanding of the protective effects and safety of 23-valent pneumococcal polysaccharide vaccine (PPV23) in immune-deficient populations, the vaccination rate of PPV23 among HIV-infected patients is still very low in China. The main objectives of this study were to determine whether the efforts to assess measures for the prevention of pneumococcal pneumonia are still worthwhile, and provide designated vaccination program of HIV-infected persons for government policy based on. Methods60 HIV-infected adults in Lanshan county who had never been vaccinated with any pneumococcal vaccine were enrolled in this study, voluntary vaccination of PPV23 and One-year follow-up after vaccination can be completed. Result76.67% patients (46/60) had serologic response at 12 months after vaccine, CD4 count(≤500 cells/ul or > 500 cells/ul) and Month from diagnosis to first antiviral therapy (≤1 month or > 1 month) were related to antibody responses (p < 0.05).In this study, PPV23 was well tolerated, no adversereaction was reported.11 Streptococcus pneumoniae pneumonia (9.17%,11/120) occurred in the Unvaccinated group and 1 case(1.67%,1/60)in the vaccination group within one year after vaccination(Fisher's exact probability, P = 0.225). The VE was 81.79%. The per capita benefit was 39.32 dollars, thebenefit-costratio = 1.19. There are significant statistical differences between the vaccinated group and the non-vaccinated group in outpatient costs (p < 0.05, 95 %CI: 9.29–32.11), Medicine costs (p = 0.017, 95 %CI: 2.47–24.44), and disease related indirect costs (p = 0.038, 95 %CI: 0.93–33.63) within one year of vaccination. ConclusionOur study results showed that PPV23 can be safely and effectively administered to HIV-1 infected individuals and effectively preventing Streptococcal pneumonia. Considering the cost-benefit of vaccination among HIV-infected persons, as it has been reported in our study, it is necessary to promote the widespread use of the vaccine among HIV-infected persons in the future.

The level of naturally occurring anti-αGal antibody predicts antibody response to polysaccharide vaccination in HIV-infected adults.

In clinical practice, the capacity for producing anti-carbohydrate antibodies is regarded as an entity, but supportive evidence is lacking. We hypothesized that the outcome of the gold standard test for clinical assessment of this capacity, antibody response to polysaccharide vaccination, correlated with the level of the abundant naturally occurring anti-carbohydrate antibody, anti-αGal. To perform an exploratory study, 47 HIV-infected adults were recruited from a vaccine trial. Participants received a 23-valent pneumococcal capsular polysaccharide vaccine. Plasma samples obtained just before and median 4weeks after the vaccination were quantified for IgG anti-αGal antibody and IgG antibodies to polysaccharides present in the vaccine (serotypes 1, 7F and 19A) by solid-phase type immunoassays. The vaccination responses were assessed as a categorical variable (based on criteria defined by The American Academy of Allergy, Asthma & Immunology and the American College of Allergy, Asthma & Immunology) and as three different continuous variables (antibody increment, geometrical average and standard normal deviates of the achieved antibody concentrations). The baseline anti-αGal level predicted the vaccine response as a categorical variable (ROC-curve analysis, AUC=0.71; 95%CI: 0.55-0.86) and as the three continuous variables (eg slope of linear regression of geometrical average=0.37; 95%CI: 0.15-0.59). The correlation between the anti-αGal level and antibody responses to polysaccharide vaccination fits with a shared underlying capacity. Thus, the present study supports the notion of a measurable capacity for the production of anti-carbohydrate antibodies in each individual. Firm conclusions on the generalizability and clinical utility require further studies.

A Japanese nationwide survey of 23-valent pneumococcal capsular polysaccharide vaccine (PPSV23) revaccination coverage rate among elderly adults aged 65 and older and physician’s attitude

ABSTRACT In July 2017, the Japanese Association for Infectious Diseases issued guidance for the administration of the PPSV23 revaccination. Despite increasing recognition of its protective benefits, levels of PPSV23 revaccination coverage rate in Japanese elderly population are unclear at present. Here, we report the results of a survey to know PPSV23 revaccination rates among elderly patients aged 65 and older. We asked an array of questions related to PPSV23 revaccination to Elderly adults and doctors across Japan via Web-based surveys in June 2018. The sampled population consisted of 5,085 men and women aged 65 and older. The PPSV23 revaccination coverage rate was estimated by survey questions regarded vaccination counts, intervals, and vaccine type. In addition, 400 internal medicine physicians were surveyed and asked about their reasons for recommending PPSV23 revaccination to elderly patients. In total, 1,648 elderly adults had received at least one PPSV23 dose; of these, 58 had received it at least twice (revaccination coverage rate: 3.5%). The most commonly cited justification for revaccination with PPSV23 among the surveyed physicians was that the benefits of revaccination exceed the risks of revaccination. In addition, multivariate analysis showed revaccinated status was most strongly associated with recommendations from peers (e.g. spouse, family, friends) among elderly subjects. This study reports PPSV23 revaccination coverage rate among Japanese adults aged 65 and older for the first time and concludes that the coverage rate is very low.

A Japanese nationwide survey of 23-valent pneumococcal capsular polysaccharide vaccine (PPSV23) coverage among patients with chronic medical condition aged 50 and older

ABSTRACT The 23-valent capsular polysaccharide pneumococcal vaccine (PPSV23) was introduced in Japan’s routine immunization schedule October 2014. It was recommended for adults aged 65 years (including those ≥65 during the transition period), and for adults 60–64 with cardiac, renal, or respiratory dysfunction equivalent to Level 1 physical disability. Several studies have shown that patients aged 50+ with chronic medical conditions (CMC) are at elevated risk of pneumococcal infection. Nonetheless, PPSV23 vaccination rates among this population remains low. In our study, we report the results of a survey investigation into PPSV23 vaccination rates among Japanese patients aged 50+ with CMC. Patients aged 50+ comprised the patient population (n = 5,078) and internal medicine physicians comprised the doctor population (n = 400) located all over Japan were asked an array of questions relevant to PPSV23 immunization in June 2018 via Web-based surveys. PPSV23 coverages among chronic patients aged 50–59, 60–64, and 65+ years were respectively 1.3%, 2.9%, and 37.8%. The high disease-specific PPSV23 rates seen in the 65+ group was 50.0% and 49.4%, for chronic liver disease and chronic lung disease, respectively. Doctors most frequently cited a lack of municipal subsidies as justification for recommending the vaccine to patients with CMC aged 50–64 years, and deference to patients’ wishes as justification for patients with CMC aged 65+. In conclusion, PPSV23 has poor coverage among Japanese adults aged 50–64 with CMC. Doctors and local authorities need to raise public awareness to improve the vaccination rate, given the high risk of pneumococcal infectious disease among patients with CMC.

Removal of cell wall polysaccharide in pneumococcal capsular polysaccharides by selective degradation via deamination

Pneumococcal cell wall polysaccharide (C–PS), a contaminant in pneumococcal capsular polysaccharide (Pn-PS) vaccines is degraded by mild deamination of the 4-amino-2-acetamido-2,4,6-tri-deoxy-galactose (AAT) in C–PS, which was carried out by addition of 5% aqueous sodium nitrite to a solution of polysaccharide in 5% aqueous acetic acid. Glycosidic linkage and functional groups such as O-acetates, phosphodiesters, and pyruvates were preserved under the conditions. The small fragments from degraded C–PS were removed by ultrafiltration or dialysis to provide essentially C–PS free Pn-PS. Because of the presence of AAT in its structure the deamination is not suitable for the purification of type 1 Pn-PS. Meanwhile, the mass and NMR spectroscopic analysis on the deamination products suggests that both type 1 Pn-PS and C–PS degraded following a major pathway of 5,4-hydride shift, cleavage of AAT O5-C1 bond, C1 hemiacetal formation, and its hydrolysis to release neighboring GalA- in type 1 Pn-PS and GalNAc(6-O-PCho)- in C–PS.

Unveiling Unexpected Immune Activities Induced by Your Pneumococcal Vaccine.

ABSTRACTIn modern-day vaccine design, a good pneumococcal capsular polysaccharide vaccine is measured by its ability to induce opsonic antibodies. These antibodies label bacteria for phagocytosis by neutrophils and thereby overcome the capsule’s barrier function. Doyle and Pirofski have raised a serious challenge to the current paradigm by describing anti-capsular antibodies that are highly protective but nonopsonic [C.R. Doyle and L. Pirofski, mBio 7(1):e02260-15, 2016, doi:10.1128/mBio.02260-15]. In fact, some functions are not related to neutrophils or phagocytosis at all. An increased awareness of these activities is critical not only for accurate comparisons of vaccine candidates but also for improvements in vaccination outcomes in settings of neutropenia. When vaccine developers select a single gatekeeper assay (e.g., an opsonophagocytic assay for bacteria or a neutralization assay for viruses), promising vaccine candidates may be missed. Doyle and Pirofski stress that multiple functions, not just one, should be investigated to enhance discovery of antibody mechanisms and to best assess vaccine-induced correlates of immune protection.

Serological response following re-vaccination with Salmonella typhi Vi-capsular polysaccharide vaccines in healthy adult travellers

An injectable Vi-capsular polysaccharide vaccine against typhoid fever is available but vaccine-induced immunity tends to wane over time. The phenomenon of immunotolerance or hyporesponsiveness has earlier been described for polysaccharide vaccines such as pneumococcal capsular polysaccharide vaccine and some publications also suggest a possible immunotolerance after revaccination with Vi-capsular polysaccharide vaccines.In this study, post-immunisation antibody concentrations in adult travellers first vaccinated with a Salmonella typhi Vi-capsular polysaccharide vaccine (primary vaccination group) were compared with those having received one or more vaccinations previously (multiple vaccinations group). Vaccines administered were Typherix® (GlaxoSmithKline), Typhim Vi® (Sanofi Pasteur MSD) or Hepatyrix® (GlaxoSmithKline). Blood samples were obtained prior to vaccination (day 0) and on day 28 (−1/+14) after vaccination. Serum Vi-Antigen IgG concentrations were measured by ELISA.Of the 85 subjects included in the per protocol data set, 45 (53%) belonged to the multiple vaccinations group. In both groups, geometric mean antibody concentrations (GMCs) were significantly higher after vaccination than before vaccination. Pre-vaccination GMCs were lower in the primary vaccination group than in the multiple vaccinations group (3.40μg/ml versus 6.13μg/ml, P=0.005), while there was no significant difference in the post vaccination GMCs between groups (11.34μg/ml versus 14.58μg/ml, P=0.4). In the multiple vaccinations group, vaccination was performed 18 to 57 months after the last vaccination (median 38 months) and there was a negative correlation between time since last vaccination and antibody concentration on day 0.In conclusion, we were not able to demonstrate a relevant immunotolerance after multiple versus primary vaccination with S. typhi Vi-capsular polysaccharide vaccines.

Response to pneumococcal vaccination in mannose-binding lectin-deficient adults with recurrent respiratory tract infections

Mannose-binding lectin (MBL)-deficiency is associated with an increased susceptibility to pneumococcal infections and other forms of disease. Pneumococcal vaccination is recommended in MBL-deficient patients with recurrent respiratory tract infections (RRTI). The response to pneumococcal vaccination in MBL-deficient individuals has not yet been studied in detail. An impaired response to pneumococcal polysaccharides in MBL-deficient patients might explain the association between MBL deficiency and pneumococcal infections. This study investigates the antibody response to pneumococcal vaccination in MBL-deficient adult patients with RRTI. Furthermore, we investigated whether there was a difference in clinical presentation between MBL-deficient and -sufficient patients with RRTI. Eighteen MBL-deficient and 63 MBL-sufficient adult patients with RRTI were all vaccinated with the 23-valent pneumococcal polysaccharide vaccine and antibodies to 14 pneumococcal serotypes were measured on a Luminex platform. There were no differences observed in the response to pneumococcal vaccination between MBL-sufficient and -deficient patients. Forty-three MBL-sufficient patients could be classified as responders to pneumococcal vaccination and 20 as low responders, compared to 15 responders and three low responders in the MBL-deficient patients. We found no clear difference in clinical, radiological, lung function and medication parameters between MBL-sufficient and -deficient patients. In conclusion, our study suggests that MBL-deficient adults with RRTI have a response to a pneumococcal capsular polysaccharide vaccine comparable with MBL-sufficient patients. Moreover, we did not find a clear clinical role of MBL deficiency in adults with RRTI. As MBL deficiency is associated with an increased susceptibility to pneumococcal infections, pneumococcal vaccination might be protective in MBL-deficient patients with RRTI.

Immunogenicity and safety of 23-valent pneumococcal polysaccharide vaccine as a booster dose in 12- to 18-month-old children primed with 3 doses of 7-valent pneumococcal conjugate vaccine

The current study examined the safety and immunogenicity of 23-valent pneumococcal capsular polysaccharide vaccine (Pneumo23® [PPV23], Sanofi Pasteur) as a booster dose in 12- to 18-month-old children primed with heptavalent pneumococcal vaccine (PCV7; Prevnar®, Pfizer). This was a randomized, observer-blinded, 2-arm, controlled, multicenter phase III study performed in Thailand to assess and describe the immunogenicity and safety of PPV23 as a booster dose in children who had received the 3 primary doses of PCV7, the pneumococcal vaccine available during the study period. Children primed with 3 doses of PCV7 were randomized 1:1 to receive a booster immunization with PPV23 or PCV7. Pneumococcal antibody concentrations were measured by enzyme-linked immunosorbent assay and functional antibody levels by multiplex opsonophagocytosis assay on day 30. A total of 339 children were enrolled. Geometric mean serum antibody concentrations against serotypes common to PCV7 and PPV23 (4, 6B, 9V, 14, 18C, 19F, and 23F) increased in both groups but they were higher for serotypes 4, 9V, 18C, and 19F in the PPV23 group. Opsonization indices increased in both groups for all measured serotypes (1, 6B, 14, 19A, and 23F) and were higher for serotypes 6B, 14, and 23F in the PCV7 group and for serotypes 1 and 19A in PPV23 group. Solicited reactions and unsolicited adverse events were similar in the 2 groups and generally mild and transient. No treatment-related serious adverse events were reported. These results confirm that boosting with PPV23 is immunogenic and well tolerated in healthy toddlers primed with PCV7.

Evaluation of humoral immune function in patients with chronic idiopathic thrombocytopenic purpura.

Coincidence of autoimmune diseases such as immune thrombocytopenic purpura (ITP) with immunodeficiencies has been reported previously in patients who suffered from primary antibody deficiency (PAD). But there is no original study on immunological profiles of ITP patients to find out their probable immune deficiency. In this case-control study, ITP patients' humoral immunity was investigated for diagnosis of PAD in comparison with normal population. To evaluate the humoral immune system against polysaccharide antigens, patients' serum immunoglobulin levels were measured and a 23-valent pneumococcal capsular polysaccharide vaccine (PPV23) was administrated to evaluate the antibody response to vaccination. In this study, 14 out of 36 patients (39%) were diagnosed with antibody mediated immune deficiency including 2 patients (5.5%) with immunoglobulin class deficiency and 4 (11%) with IgG subclass deficiency. The remaining patients suffered from specific antibody deficiency. The most frequent deficiency in ITP patients was specific antibody deficiency.Therefore, immunological survey on ITP patients may be important especially for those who have undergone splenectomy.

102 Maintenance of Antibody Response to Pneumococcal Capsular Polysaccharide Vaccination in Adult Patients after Heart Transplantation

Purpose: The aim of this study was to evaluate the maintenance of antibody response to unconjugated pneumococcal capsular polysaccharide vaccine (PPV23) in adult heart recipients. Methods and Materials: 37 heart recipients (mean age 52 10) that were vaccinated with PPV23 at the time of inclusion in the waiting list, and 29 unvaccinated healthy controls (mean age 46 9 years) were analysed. Blood samples were taken pre-HT before vaccination (n 16) and after vaccination (n 17, mean time from vaccination: 143 days). Study points after HT: 7days (n 34), 1m (n 34), 3m (n 37), 6m (n 37), 12m (n 33) and 18m (n 22). Specific antibodies were measured using a commercial enzyme-linked immunosorbent assay technique (ELISA, Binding Site, Birmingham, UK; measuring range: 0.33-27 mg/dl). Results: In the pre-HT evaluation anti-PPS concentrations before vaccination were similar in heart recipients and controls (10 9 vs 10 8 mg/dl). After vaccination heart recipients disclosed significantly higher concentrations than controls: before HT (27 0.9, p 0.001,) and at 7days (20 8, p 0.001), 1m (19 9, p 0.001), 3m (18 9, p 0.001), 6m (16 9, p 0.005), and 12m (14 9, p 0.045) after-HT. There were no significant differences between both groups at 18m (12 9, p 0.21). Median fold increase of anti-PPS was 4.56 (pre-HT vs 7 days, interval: 0.54-17.42). There was a progressive decrease in anti-PPS which were significantly lower as compared with baseline post-vaccination values at all post-HT study points. During follow-up, 8 patients (20.5%) developed bacterial infectious complications. The frequency of heart recipients that maintained anti-PPS concentrations higher than 27 mg/dl during the first 3 months was 12.5% and 48% in patients with and without bacterial infections, respectively (p 0.07). Conclusions: Heart recipients maintained higher concentrations of antiPPS as compared with unvaccinated healthy controls up to 18 months after transplantation. Lower concentrations of anti-PPS mignt be associated with development of bacterial infections.

Characterization of Gene Use and Efficacy of Mouse Monoclonal Antibodies toStreptococcus pneumoniaeSerotype 8

Streptococcus pneumoniae is the most common cause of community-acquired pneumonia in the United States and globally. Despite the availability of pneumococcal capsular polysaccharide (PPS) and protein conjugate-based vaccines, the prevalence of antibiotic-resistant pneumococcal strains, serotype (ST) replacement in nonconjugate vaccine strains, and uncertainty as to whether the PPS vaccine that is used in adults protects against pneumonia emphasize the need for continued efforts to understand the nature of protective PPS antibody responses. In this study, we generated mouse monoclonal antibodies (MAbs) to a conjugate consisting of the PPS of serotype 8 (PPS8) S. pneumoniae and tetanus toxoid. Thirteen MAbs, including four IgMs that bound to PPS8 and phosphorylcholine (PC) and five IgMs and four IgG1s that bound to PPS8 but not PC, were produced, and their nucleotide sequences, epitope and fine specificity, and efficacy against lethal challenge with ST8 S. pneumoniae were determined. MAbs that bound to PPS8 exhibited gene use that was distinct from that exhibited by MAbs that bound to PC. Only PPS8-binding MAbs that did not bind PC were protective in mice. All 13 MAbs used germ line variable-region heavy (V(H)) and light (V(L)) chain genes, with no evidence of somatic hypermutation. Our data reveal a relationship between PPS specificity and V(H) gene use and MAb efficacy in mice. These findings provide insight into the relationship between antibody molecular structure and function and hold promise for the development of novel surrogates for pneumococcal vaccine efficacy.

Antibody response to pneumococcal capsular polysaccharide vaccination in patients with chronic kidney disease

Patients with chronic kidney disease (CKD) or on dialysis are at greater risk of infection, which might be due to a defective immune function. While there are controversial reports on efficacy of vaccination in this group of patients, the aim of this study was to evaluate the antibody response to pneumococcal capsular polysaccharide vaccine (PPV23) in CKD patients. Sixty-six patients with CKD and 40 healthy individuals were vaccinated with PPV23. Blood samples were taken before and four weeks after vaccination. Specific antibodies against whole pneumococcal antigens were measured using an enzyme-linked immunosorbent assay (ELISA) technique. Among the 66 vaccinated patients, 14 (21%) were hypo-responsive to vaccine (group 1), while 52 had a normal specific-antibody response (group 2). Post-vaccination, anti-pneumococcal IgG titers in group 1 were significantly lower than those in group 2 (p = 0.012 for IgG post-vaccination and p = 0.020 for IgG2 post-vaccination). The fold increase or ratio increase of the anti-pneumococcal IgG titer in patients of group 1 was also significantly lower than that in group 2 or the healthy control group (p = 0.001 versus group 2 and p = 0.005 versus control group). During follow-up of both patient groups, group 1 patients developed more episodes of pneumococcal infections than those patients in group 2 (p = 0.007). In conclusion, although the majority of patients with CKD were responders to the polysaccharide vaccine, a substantial proportion of patients failed to mount an adequate antibody response to PPV23 and remained at significant risk of pneumococcal infection. Nevertheless, this vaccination policy should be administered as it could prevent infection in responder patients.

Ineffectiveness for infants of immunization of mothers with pneumococcal capsular polysaccharide vaccine during pregnancy

Pneumococcal (Pnc) carriage is associated with pneumococcal diseases. Breast feeding and maternal vaccination may be a useful approach to prevent pneumococcal infection in young infants. We examined the risk of Pnc carriage by infants at six months of age after pneumococcal polysaccharide vaccination of pregnant women. We selected 139 pregnant woman. The woman were randomly allocated to receive 23-valent polysaccharide vaccines during pregnancy (Group 1) after pregnancy (Group 2) or not receive any vaccine (Group 3). Nasopharyngeal swabs were collected from the infants at three and six months of age. The infants were evaluated monthly during the first six months. We included 47 mothers in Group 1, 45 mothers in Group 2 and 47 mothers in Group 3. Forty-seven percent of the babies were exclusively breast fed until six months, 26% received both breast feeding and artificial feeding and 13% received only artificial feeding. Among those patients, 26% were colonized by Pnc at six months (12 from Group 1, 13 from Group 2, and 12 from Group 3). There was no significant difference in colonization between the three groups. Thirty percent of the children were colonized by a non-susceptible strain. We concluded that young infants (three months old) are already susceptible to pneumococcal carriage. Vaccination during pregnancy with a polysaccharide vaccine did not decrease Pnc colonization.

Inhaled delivery of 23-valent pneumococcal polysaccharide vaccine does not result in enhanced pulmonary mucosal immunoglobulin responses

We compared the effect of intramuscular vs. inhaled 23-valent pneumococcal capsular polysaccharide vaccine (23-PPV) on pulmonary mucosal immunoglobulin levels. Bronchoalveolar lavage (BAL) and serum were collected from 33 adults before and 1 month after injected (n=16) or inhaled (n=17) 23-PPV. Levels of pneumococcal capsule-specific IgG and IgA to types 1, 9V and 14 were measured in each sample. Injected 23-PPV produced a significant increase in types 1, 9V and 14 capsule-specific IgG and type 1 IgA in both serum and BAL (type 1 geometric mean BAL IgG 9.8ng/ml post-vaccine vs. 5ng/ml pre-vaccine, p=0.01; type 9V geo mean 5.6ng/ml vs. 2.7ng/ml, p=0.001; type 14 geo mean 23.6ng/ml vs. 6.2ng/ml, p=0.02). Inhaled vaccine produced no response in either BAL or serum.

Class- and subclass-specific pneumococcal antibody levels and response to immunization after bone marrow transplantation.

Immunoglobulin class- and subclass-specific antibodies to a polyvalent pneumococcal capsular polysaccharide vaccine (Pneumovax II) were measured before and after immunization in children, 1 year or more after bone marrow transplantation for a variety of genetic disorders. The median titres of specific IgG, IgG1 and IgG2 pneumococcal antibodies fell significantly (P less than 0.05) from pre-transplantation levels. The levels of pneumococcal antibodies in the patients before immunization were markedly lower than those in control children of comparable age, for antibodies of IgM, IgG, IgG1 and IgG2 classes (P = less than 0.001 in each case). Apart from IgG2 antibodies, the median response to immunization with Pneumovax II was not significantly different from the controls (P greater than 0.05). However, because of the lower pre-immunization levels, the patients did not achieve a high post-immunization-specific antibody titre in any immunoglobulin class or subclass, when compared with normal children. Neither the pre-immunization specific antibody levels nor the response to immunization were affected by splenectomy or the presence of chronic graft-versus-host disease. Immunization of the donor before bone marrow harvest did not influence the level of specific antibody 1 year or more after transplantation. No significant correlation was found between the total serum IgG2, the patients' age at the time of assessment, or time after transplantation, and the IgG2-specific antibody response. The lack of specific antibodies and the poor IgG2 response to pneumococcal antigens may contribute towards the occurrence of infection with Streptococcus pneumoniae in the late post-transplantation period.

Assessment of the Protective Effect of Pneumococcal Vaccination in Preventing Meningitis After Cochlear Implantation

To examine if a 23-valent pneumococcal capsular polysaccharide vaccine (PPV23) reduces the risk of meningitis in healthy rats after cochlear implantation. Interventional animal study. Thirty-six rats (18 immunized and 18 unimmunized) received cochlear implantations and were then infected with Streptococcus pneumoniae via 3 different routes (hematogenous, middle ear, and inner ear) in numbers sufficient to induce meningitis. The rats with implants that received PPV23 were protected from meningitis when the bacteria were delivered via the hematogenous and middle-ear routes (Fisher exact test P<.05). However, the protective effect of the vaccine in the rats with implants was only moderate when the bacteria were inoculated directly into the inner ear. Our animal model clearly demonstrates that immunization can protect healthy rats with a cochlear implant from meningitis caused by a vaccine-covered serotype. This finding supports the notion that all current and future implant recipients should be vaccinated against S pneumoniae.

Pneumococcal capsular polysaccharide vaccine-mediated protection against serotype 3 Streptococcus pneumoniae in immunodeficient mice.

Pneumococcal capsular polysaccharide (PPS) vaccines are less immunogenic in immunocompromised than immunocompetent individuals. However, neither the efficacy of PPS vaccines in immunocompromised individuals nor the host cellular subsets required for vaccine efficacy against pneumococcal disease have been directly investigated. In this study, we vaccinated CD4-deficient (CD4(-/-)), CD8-deficient (CD8(-/-)), and secretory immunoglobulin M-deficient (sIgM(-/-)) mice and wild-type C57BL/6 (Wt) mice with a conjugate of PPS of serotype 3 and tetanus toxoid (PPS3-TT) and determined the antibody response and efficacy of vaccination against systemic and pulmonary challenge with serotype 3 pneumococcus in immunized and control mice. Our results showed that the isotype and predominant IgG subclass of the PPS3 response differed between immunodeficient mouse strains and between immunodeficient and Wt mice, with CD8(-/-) mice having the most robust response. Vaccination protected Wt, CD4(-/-), and sIgM(-/-) mice from death resulting from both systemic and pulmonary challenge, whereas CD8(-/-) mice were protected only from systemic and not from pulmonary challenge. Passive vaccination with PPS3-TT-induced sera from Wt, CD4(-/-), CD8(-/-), and sIgM(-/-) mice protected naïve Wt mice from death due to pulmonary challenge; however, CD8(-/-) mice were not protected by sera from Wt or CD8(-/-) mice. Our findings suggest that PPS-based vaccines can be effective in the setting of CD4 T-cell deficiency but that CD8 T cells could be required for vaccine-mediated protection against pulmonary challenge with serotype 3 pneumococcus.

Antibody response to pneumococcal capsular polysaccharide vaccine in Down syndrome patients

The majority of children with Down syndrome (DS) tend to have frequent bacterial infections including recurrent respiratory infections. Our objective was to evaluate the production of antibodies to pneumococcal polysaccharide antigens after active immunization in DS subjects. IgG antibodies to pneumococcal serotypes (1, 3, 6B, 9V, and 14) were measured before and 6 weeks after immunization with a 23-valent pneumococcal vaccine (Pneumo23, Pasteur-Merrieux) in 6- to 13-year-old DS children (N = 17) and in aged-matched normal controls (N = 30). An adequate response was defined as a 4-fold increase over baseline or a post-immunization level of specific pneumococcal serotype antibody > or = 1.3 microg/mL. After immunization, all DS children had an increase in post-immunization levels against all serotypes analyzed. A 4-fold or more increase was observed in all DS children concerning serotypes 1 and 14, in 90% of subjects for serotypes 3 and 9V, and in 65% for serotype 6B. Regarding this increase, 8 of the 17 DS children had an adequate response to all serotypes analyzed, 8/17 patients to 4 serotypes and 1/17 to 3 serotypes. However, when we compared post-immunization levels between DS children and controls, we observed lower levels in the former group (P < 0.05) for all serotypes except serotype 3. We conclude that pneumococcal polysaccharide immunization could be beneficial for these DS children.