23-valent Pneumococcal Capsular Polysaccharide Vaccine Research Articles

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.

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.

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.

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.

Effect of Pneumococcal Vaccination: A Comparison of Vaccination Rates in Patients with Bacteremic and Nonbacteremic Pneumococcal Pneumonia

Despite the widespread acceptance of the 23-valent pneumococcal capsular polysaccharide vaccine (PPV), its protective effect continues to be disputed. We describe a novel approach to examine the protective effect of this vaccine. We recorded the vaccination status of every patient for whom a culture yielded Streptococcus pneumoniae during a 4.5-year period, comparing rates of prior PPV administration in patients with (1) bacteremic pneumococcal pneumonia, (2) all-invasive pneumococcal disease, (3) nonbacteremic pneumococcal pneumonia, (4) acute exacerbation of chronic bronchitis (AECB) due to S. pneumoniae, and (5) pneumococcal colonization. The principal comparisons were with patients who had bacteremic pneumonia or any invasive pneumococcal disease and those with nonbacteremic pneumococcal pneumonia. We also compared vaccination rates in patients who had nonbacteremic pneumonia with vaccination rates in patients with AECB or pneumococcal colonization. The rate of prior PPV vaccination was lower among patients with bacteremic pneumococcal pneumonia (39.7%) or any invasive pneumococcal disease (38.0%) than among patients with nonbacteremic pneumonia (57.6%), AECB (60.0%), or pneumococcal colonization (57.8%). PPV conferred a 54% protection rate against bacteremic versus nonbacteremic pneumococcal pneumonia. There was no apparent protection against nonbacteremic pneumonia compared, for example, with colonized persons or with those who had AECB. PPV provides moderate protection against invasive pneumococcal disease but does not protect against nonbacteremic pneumococcal pneumonia. These findings suggest the importance of a continued search for a better pneumococcal vaccine.

Treatment of acute exacerbation of severe-to-very severe COPD with azithromycin in patients vaccinated against Streptococcus pneumoniae

Sixty-five consecutive eligible adult patients, who were treated as outpatients for stable severe-to-very severe COPD, were enrolled in the study. All of them received 23-valent pneumococcal capsular polysaccharide vaccine intramuscularly. Patients were seen monthly, as well as whenever they had symptoms suggestive of an exacerbation, at our outpatient clinic. Eighteen out of 65 patients suffered from acute exacerbation (AECOPD). Three of these patients presented two episodes of AECOPD. Patients with an acute exacerbation of COPD received azithromycin 500 mg/day once daily for 3 days and a short course of oral prednisolone 25 mg/die. In 16 cases, a single species was isolated, while in the remaining 5 cases at least two species were recovered. Clinical cure or improvement at the end of therapy (3-5 days post-therapy) was reported in 17 episodes of AECOPD with no relapse at the late post-therapy (10-14 days after the completion of treatment). Bacteriologic eradication or presumptive eradication rates at the end of therapy were 86% (24 out of 28 isolates). Azithromycin eradicated all isolates of Haemophilus influenzae, Moraxella catarrhalis, H. parainfluenzae, Klebsiella pneumoniae, and Klebsiella spp. isolated at baseline. Eradication of Sta aureus occurred in 1 of 3 isolates whereas azithromycin was unable to eradicate Pseudomonas aeruginosa isolates. Our data seem to indicate that pneumococcal vaccination reduces the possibility that an AECOPD is caused by Streptococcus pneumoniae. This finding allows the use of antibiotics such as azithromycin, which, otherwise, should be avoided because of resistances.

Antibody Response to Pneumococcal Polysaccharide Vaccination Predicts Pneumococcal Disease in Splenectomized Patients with Hematological Diseases.

Patients with hematological diseases undergoing diagnostic or therapeutic splenectomy are at increased risk of acquiring fulminant pneumococcal infections. Vaccination is a straightforward option in reducing these infections. Certain patient subgroups showing inadequate immunological response to pneumococcal vaccination may be candidates for alternative prophylactic measures. We prospectively studied the antibody response to vaccination with 23-valent pneumococcal capsular polysaccharide vaccine (Pneumovax N) in splenectomized patients with hematological disorders in relation to clinical characteristics and pneumococcal disease. A total of 76 splenectomized patients (Hodgkin s lymphoma 26, indolent lymphoma 10, aggressive lymphoma 8, immune hemolytic anemia 6, immune thrombocytopenic purpura 22, and others 4) with a median age of 52 years (range 18–82) were included. Antibody titers were determined using an enzyme-linked immunosorbent assay before and 12 months after vaccination. A weak immunological response was observed in 27 (35%) patients (poor responders) and an adequate response in 49 (65%) (good responders). During the follow-up period of 5–9 years after vaccination and despite repeated revaccination in many cases, a total of 5 episodes of microbiologically verified pneumococcal infections were reported in poor responders, while only one episode was noted among good responders (p=.01). Underlying malignant hematological diseases were more frequent among poor responders than among good responders (p=.002). The distribution of patients according to age, gender, immunoglobulin levels, time between splenectomy and vaccination (<1 year>), time between preceding chemotherapy/radiotherapy and vaccination (<6 months>) and/or previous radiotherapy did not differ between poor and good responders. In conclusion, a significant number of splenectomized patients with hematological diseases respond poorly to pneumococcal vaccination and have a significantly increased risk of post-splenectomy pneumococcal infections despite vaccination. In the absence of clinical parameters that can reliably predict a poor antibody response, measurement of antibody titers 12 months after vaccination seems to be the most adequate method for identification of patients in this subgroup. Poor responders may be offered other prophylactic measures such as antibiotic prophylaxis and/or immunization with pneumococcal conjugate vaccines. Studies to further elucidate the last alternative are ongoing.

Qualitative change in antibody responses of human immunodeficiency virus-infected individuals to pneumococcal capsular polysaccharide vaccination associated with highly active antiretroviral therapy.

Variable region gene family 3 (V(H)3) is the predominant immunoglobulin (Ig) gene family used in human antibodies to pneumococcal capsular polysaccharide (PPS). This study examined whether highly active antiretroviral therapy (HAART) restores the ability of human immunodeficiency virus (HIV)-infected individuals to generate a V(H)3-positive response to PPS. The IgM, IgG, and V(H)3 (represented by antibodies expressing the determinant recognized by the monoclonal antibody D12) responses to PPS were determined for first-time recipients of a 23-valent PPS vaccine, both receiving and not receiving HAART, and second-time vaccine recipients receiving HAART. The results showed that only the individuals receiving HAART manifested a V(H)3-(D12)-positive response to PPS, despite a similar IgG response in each group. There was also a negative correlation between HIV load and PPS response for the groups receiving HAART. These findings suggest that HAART may influence qualitative aspects of the PPS response by restoring expression of certain V(H)3 genes used in the normal PPS response.

Epidemiology of emerging pneumococcal drug resistance: implications for treatment and prevention

Drug-resistant Streptococcus pneumoniae infection are becoming increasingly common throughout the world. These strains pose new challenges in the treatment of suspected pneumococcal infections, and they highlight the importance of limiting selection for resistant strains through judicious antibiotic use and preventing infection by immunization of persons at high risk. The clinical impact of drug-resistant S. pneumoniae infection has not been fully defined, but anecdotal reports suggest that outcome is poor for persons with drug-resistant pneumococcal meningitis. The American Academy of Pediatrics has recommended adding vancomycin to the treatment of suspected pneumococcal meningitis cases until the results of culture and susceptibility testing are available. Additional data are needed to determine the optimal empiric antibiotic regimen for nonmeningeal invasive pneumococcal imfections. A 23-valent pneumococcal capsular polysaccharide vaccine can prevent many drug-resistant and susceptible invasive pneumococcal infections. The vaccine is recommended in the United States for persons at increased risk of pneumococcal infeaction due to certain medical conditions and for all persons ≥65 years old. Vaccine efficacy for immunocompetent persons ≥65 years is 75%. However, the vaccine is underutilized, and a substantial reduction in the morbidity and mortality associated with invasive pneumococcal infections is unlikely until the vaccine is used more widely among persons at risk for disease.

Randomised trial of 23-valent pneumococcal capsular polysaccharide vaccine in prevention of pneumonia in middle-aged and elderly people

We assessed the effectiveness of a 23-valent pneumococcal vaccine in the prevention of pneumococcal pneumonia and of pneumonia overall in non-immunocompromised middle-aged and elderly people. The prospective, multicentre, double-blind, randomised, placebo-controlled trial was carried out across departments of infectious diseases at six tertiary-care or university hospitals in Sweden. 691 non-immunocompromised patients aged 50-85 years who had been treated as inpatients for community-acquired pneumonia (CAP) were randomly assigned either 23-valent pneumococcal capsular polysaccharide vaccine or placebo (sodium chloride). We used Cox regression models to estimate the relative risks of pneumonia overall and pneumococcal pneumonia for the placebo group compared with the vaccine group. 63 (19%) of 339 patients in the vaccine group and 57 (16%) of 352 patients in the placebo group developed a new pneumonia, corresponding to a relative risk over time for the placebo group compared with the vaccine group of 0.83 (95% CI 0.58-1.12, p=0.31). Pneumococcal pneumonia was diagnosed in 16 (4.5%) patients in the placebo group and in 19 (5.6%) in the vaccine group, corresponding to a relative risk for the placebo group of 0.78 (95% CI 0.40-1.51, p=0.45). We found no difference in the death rate between the two study groups. The 23-valent pneumococcal polysaccharide vaccine did not prevent pneumonia overall or pneumococcal pneumonia in middle-aged and elderly individuals.

Immunoglobulin deficiencies and impaired immune response to polysaccharide antigens in adult patients with recurrent community-acquired pneumonia.

The frequency of humoral immunodeficiencies was analysed in 39 patients with a history of recurrent (> or = 3) episodes of community-acquired pneumonia. Total immunoglobulin levels and/or IgG subclass levels were low in 14 patients (36%), including eight patients with IgG or IgG2 deficiency. The specific antibody activity to pneumococcal capsular polysaccharides (serotypes 3, 6A, 19F, and 23F) and to phosphorylcholine was low in the IgG/IgG2-deficient patients compared to 36 healthy controls, and they also responded poorly to vaccination with a 23-valent pneumococcal capsular polysaccharide vaccine. The remaining 25 patients, with normal immunoglobulin and IgG subclass levels, had specific anti-pneumococcal antibody levels comparable to the healthy controls, and all but 3 responded to vaccination. We conclude that immunoglobulin deficiencies and the inability to respond to polysaccharide antigens are common risk factors for recurrent pneumonia in adult patients. Immunoglobulin levels (including IgG subclasses) and antibody response to polysaccharide antigens should be investigated in these patients.

Antibody response to pneumococcal capsular polysaccharide vaccine in African children

Antibody titers to six pneumococcal polysaccharides were measured by enzyme-linked immunosorbent assay in Gambian children before and 1 month after vaccination with a 23-valent pneumococcal capsular polysaccharide vaccine at the ages of 2, 4, 6 or 9 months or at 5 to 10 years of age. IgG responses to type 1, 3 and 5 polysaccharides were seen in children in all age groups. Responses to type 19F and 23F polysaccharides were seen only in the oldest children. Few children of any age responded to immunization with type 6A pneumococcal polysaccharide. The immune response of Gambian infants to immunization with six components of a polyvalent pneumococcal polysaccharide vaccine was comparable with that described previously in Finnish infants and would be unlikely to provide substantial protection against invasive pneumococcal disease.

Serum antibodies to pneumococcal C polysaccharide in children: response to acute pneumococcal otitis media or to vaccination.

Immunoglobulin class-specific antibody responses to the pneumococcal C polysaccharide (CPS) and to the capsular polysaccharides of types 3, 6A, 18C and 19F were measured by enzyme-linked immunosorbent assay in the sera of children ages 6 months to 7 years. Twenty of these children had acute otitis media caused by pneumococci of type/group 3, 6, 18 or 19, whereas 20 received an injection of 14-valent pneumococcal capsular polysaccharide vaccine. Many of the children in both groups had large concentrations of IgG and/or IgM class anti-CPS antibodies in their first serum sample. Both the infection and the vaccine elicited anti-CPS responses in all three immunoglobulin classes, most notably IgA. The pneumococcal capsular polysaccharides used as antigens in the enzyme-linked immunosorbent assay were found to contain CPS in amounts ranging from less than 1 to 30%. As a result the enzyme-linked immunosorbent assay detected both anti-type-specific and anti-CPS antibodies. After elimination of the anti-CPS, type-specific pneumococcal antibodies were found only occasionally and in low concentrations in serum samples obtained in the acute phase of otitis or before vaccination. The infection induced homologous type-specific pneumococcal antibodies to varying degrees depending on the type: regularly to type 3; and fairly regularly to type 18C polysaccharide, but seldom to type 6 or 19. The pneumococcal vaccine induced type-specific antibodies to all four types measured, but the response to type 6A was poor.

Antibody response to 14-valent pneumococcal capsular polysaccharide vaccine in pre-school age children

Antibody responses to 14-valent pneumococcal capsular polysaccharide vaccine were measured by Farr-type radioimmunoassay in children younger than 7 years of age. On the basis of immunogenicity in young children individual pneumococcal polysaccharides could be identified as uniformly good, strongly age-dependent or uniformly poor immunogens. Pneumococcal types 6A and 23F, which frequently cause pneumococcal infections in small children, were the poorest immunogens in this age group. The children younger than 2 years of age responded very poorly also to types 19F and 18C whereas older children had good antibody responses to these types. The results support the current view that present pneumococcal polysaccharide vaccines are not beneficial in children younger than 2 years of age and stress the importance of attempts to improve their immunogenicity.

Persistence of antibodies to pneumococcal vaccine in patients with chronic renal failure

Antibody response to the 14-valent pneumococcal capsular polysaccharide vaccine was measured by the enzyme-linked immunosorbent assay (EIA) in 17 renal allograft recipients, 29 azotemic, 11 hemodialysis, and 33 control patients. The IgG, IgM, and IgA antibodies were measured against six pneumococcal antigen types 1, 3, 4, 6A, 8, and 19F. The control patients had the best antibody responses in the IgG and IgA antibody classes and the renal allograft recipients in the IgM class. The renal allograft recipients had significantly stronger antibody responses than the azotemic and hemodialysis patients. The hemodialysis patients had significantly weaker antibody responses than the control patients and the renal allograft recipients, and they also lost their antibodies most rapidly. Thus, the hemodialysis patients and probably some azotemic patients should be considered for revaccination.

Effects of 14-Valent Pneumococcal Capsular Polysaccharide Vaccine in Patients with COPD

Effects of 14-Valent Pneumococcal Capsular Polysaccharide Vaccine in Patients with COPD

Effects of 14-Valent Pneumococcal Capsular Polysaccharide Vaccine in Patients with COPD

Effects of 14-Valent Pneumococcal Capsular Polysaccharide Vaccine in Patients with COPD