Pneumococcal Serotypes 6B Research Articles

Breastfeeding enhances the antibody response to Hib and Pneumococcal serotype 6B and 14 after vaccination with conjugate vaccines

Background This study was performed in order to investigate the relationship between breastfeeding and the antibody response after vaccination with conjugate vaccines against Hib and pneumococcal diseases. Methods This was an open non-randomised multi-centre study enrolling 101 healthy Swedish infants. PncCRM was administered concomitantly with DTaP/IPV/Hib at 3, 5, and 12 months at separate site. Duration of breastfeeding was calculated for days of almost exclusive as well as of total (any form of) breastfeeding. Results At 13 months of age 6 out of 83 children did not reach 0.2 μg/ml against serotype 6B, and five of these were breastfed less than 90 days (Fisher's Exact test, P = 0.011). Four children did not reach 1 μg/ml against Hib and all those were breastfed less than 90 days (Fisher's Exact test, P = 0.008). One month after the second dose, at 6 months of age, children breastfed 90 days or more showed significantly higher GMC against serotype 14 ( P = 0.003). Conclusion This study indicates that children exclusively breastfed 90 days or more might get a better serological protection against Hib, and the pneumococcal serotypes 6B and 14 after vaccination, compared to children less breastfed.

Characterization of Antibodies to Capsular Polysaccharide Antigens ofHaemophilus influenzaeType b andStreptococcus pneumoniaein Human Immune Globulin Intravenous Preparations

The most common infections in primary immune deficiency disease (PIDD) patients involve encapsulated bacteria, mainly Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae (pneumococcus). Thus, it is important to know the titers of Hib- and pneumococcus-specific antibodies that are present in immune globulin (Ig) intravenous (IGIV) preparations used to treat PIDD. In this study, seven IGIV preparations were tested by enzyme-linked immunosorbent assay and opsonophagocytic activity for antibody titers to the capsular polysaccharides of Hib and five pneumococcal serotypes. Differences in Hib- and pneumococcus-specific antibody titer were observed among various IGIV preparations, with some products having higher- or lower-than-average titers. Opsonic activity also varied among preparations. As expected, IgG2 was the most active subclass of both binding and opsonic activity except against pneumococcal serotype 6B where IgG3 was the most active. This study determines antibody titers against capsular polysaccharides of Hib and pneumococcus in seven IGIV products that have been shown to be effective in reducing infections in PIDD patients. As donor antibody levels and manufacturing methods continue to change, it may prove useful from a regulatory point of view to reassess IGIV products periodically, to ensure that products maintain antibody levels that are important for the health of IGIV recipients.

Modification of bacteraemia by specific antibodies and relation with mortality in a pneumococcal mouse sepsis model.

The relationship between mortality and the bacteraemic profile was investigated in a pneumococcal (serotype 6B) sepsis BALB/c mouse model where animals received protection by specific hyperimmune serum. A single intraperitoneal dose of hyperimmune serum obtained from mice immunized with the heat-inactivated strain was administered (non-diluted or diluted to 1/4 or to 1/16) to 5-mice study groups 1 h prior to intraperitoneal inoculation with the infective inoculum (3.57 x 108 cfu/ml). Blood cultures were performed daily over 15 days, with 8 microl of blood being collected from the tail vein; the samples were resuspended in Todd-Hewitt broth containing 10% trisodium citrate and plated onto blood agar for colony counting. Animals included in the control group received placebo (PBS). Mortality was 100% in control animals within the first 48 h. Hyperimmune serum decreased and delayed mortality in a dose-related trend, producing 100%, 80%, 60% and 40% survival rates at 72, 96, 144 and 360 h, with non-diluted serum. Bacteraemic profiles with maximum colony counts > or =5 x 107 cfu/ml in blood during the follow-up period were related to > or =65% probability of death, regardless of the serum dilution administered.

Maternal immunization with pneumococcal polysaccharide vaccine in the third trimester of gestation

In a randomized, double blinded study, 23-valent pneumococcal polysaccharide vaccine (PSV) or conjugate Haemophilus influenzae type b (HbOC) vaccine was administered to 60 healthy women in the third trimester of gestation. Total IgG, IgG1, and IgG2 antibodies to pneumococcal serotypes 6B, 14, 19F and 23F were measured by ELISA in mothers prior to immunization, at delivery and 7 months after delivery, and in infants at birth (cord blood), 2 and 7 months after delivery. IgA was evaluated in breast milk at 2 and 7 months, and opsonophagocytic activity in cord blood. PSV was safe and immunogenic in pregnant women. Transplacental transmission of vaccine-specific antibodies was efficient. Maternal immunization with PSV resulted in significantly higher concentrations of pneumococcal antibodies in infants at birth and at 2 months of age, and greater functional opsonophagocytic activity of passively acquired IgG antibody.

Antimicrobial resistance of Streptococcus pneumoniae recovered from outpatients with respiratory tract infections in Germany from 1998 to 1999: results of a national surveillance study.

Clinically significant pneumococcal isolates were prospectively collected from outpatients with respiratory tract infections by 19 different clinical microbiology laboratories in Germany. Resistance rates in a total of 961 isolates were as follows: penicillin, 6.6%; clarithromycin, 10.6%; tetracycline, 13.9%; and levofloxacin, 0.1%. Among 324 isolates from children, pneumococcal serotypes 19F (17.0%), 23F (13.0%), and 6B (11.7%) were the predominant types.

Enhanced antibody response to pneumococcal polysaccharide vaccine after prior immunization with conjugate pneumococcal vaccine in HIV-infected adults

The antibody production by HIV-infected adults after two vaccinations with conjugated pneumococcal vaccine (CPV) and consecutive vaccination with polysaccharide pneumococcal vaccine (PPV) was studied. Thirty days after the second CPV, the geometric mean antibody concentrations (GMC) against pneumococcal polysaccharide serotypes (PPS) 6B, 14 and 19F were significantly lower in the group HIV-infected individuals with <200×10 6/l CD4 + T lymphocytes (group 1) than in the group with ⩾200×10 6/l CD4 + T lymphocytes (group 2) and healthy controls. Thirty days after PPV vaccination the GMC against PPS 6B, 14, 19F and 23F in group 1, and against 6B and 19F in group 2, were significantly lower compared with healthy controls. Both in HIV-infected and in healthy individuals who received CPV and PPV the postvaccination GMC against PPS 14, 19F and 23F were higher compared with historical controls who were not previously immunized with CPV but only received PPV. We conclude that the antibody response to CPV is impaired in HIV-infected individuals. Higher antibody concentrations were achieved in HIV-infected and healthy individuals after sequential vaccination with CPV and PPV compared with PPV vaccination alone.

Conjugate pneumococcal vaccine and antibiotic-resistant Streptococcus pneumoniae: herd immunity and reduction of otitis morbidity.

Conjugate pneumococcal vaccine and antibiotic-resistant Streptococcus pneumoniae: herd immunity and reduction of otitis morbidity.

Limited diversity of Streptococcus pneumoniae psaA among pneumococcal vaccine serotypes.

The pneumococcal surface adhesin A (PsaA) is a surface-exposed protein of the gram-positive bacterium Streptococcus pneumoniae. It belongs to a group of proteins designated the lipoprotein receptor I antigen family. The gene encoding PsaA from an encapsulated strain of pneumococcal serotype 6B was cloned and sequenced. The peptide sequence was compared to that of homologs found in S. pneumoniae serotype 2, viridans streptococci, and Enterococcus faecalis. Identity values among the deduced peptides ranged from 57 to 98%. The polymorphism of psaA was examined among the 23 encapsulated vaccine serotypes by using PCR-restriction fragment length polymorphism analysis. Ten different enzymes were used to analyze 80 strains representing the 23 serotypes in a 23-valent polysaccharide vaccine. This analysis showed that restriction sites within the gene were highly conserved, with only a minor variation occurring in 10% of the strains, the result of an additional Tsp509I site. The lack of variation for the other restriction sites within the gene examined here indicates that psaA is genetically conserved, an important characteristic necessary for a candidate common protein vaccine.

Effect of Human Immunodeficiency Virus Type 1 Infection on the Antibody Response to a Glycoprotein Conjugate Pneumococcal Vaccine: Results from a Randomized Trial

Adults (n = 282) were randomized to receive either a pneumococcal glycoprotein conjugate vaccine, composed of pneumococcal serotypes 6B, 14, 18C, 19F, and 23F linked to CRM197, or a 23-valent pneumococcal polysaccharide vaccine. Among human immunodeficiency virus (HIV)-uninfected persons, conjugate vaccine elicited significantly higher IgG antibody geometric mean titers (GMTs) than did polysaccharide vaccine for serotypes 6B, 18C, and 23F: IgG GMTs were 9.0 versus 4.8, 23.2 versus 5.9, and 15.3 versus 4.4 micrograms/mL, respectively. In contrast, the two vaccines elicited similar antibody GMTs in HIV-infected persons: GMTs ranged from 1.3 to 10.8 micrograms/mL for all serotypes. Of note, among persons receiving polysaccharide vaccine, antibody GMTs in HIV-uninfected and -infected persons with CD4 lymphocytes > or = 500/microL were similar. These data underscore the importance of controlled clinical evaluations of newer pneumococcal vaccines in all high-risk groups for whom pneumococcal immunization is recommended and highlight the need for early immunization of HIV-infected persons with currently available polysaccharide vaccines.

Beneficial effect of liposome-encapsulated muramyl tripeptide in experimental septicemia in a porcine model

In a porcine model of pneumococcal septicemia, animals were pretreated with 1 mg of liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (MTP-PE) or with liposomes alone. After 24 h each animal received an injection of either 10(9) or 10(10) pneumococcal serotype 6B cells. MTP-PE pretreatment resulted in less pronounced leukocytopenia, with a nadir of 6,700 (versus 4,100) leukocytes per mm3 after injection of 10(9) bacteria and a nadir of 4,400 (versus 3,800) leukocytes per mm3 after injection of 10(10) bacteria. At the same time bacterial clearance was substantially improved by MTP-PE pretreatment. Finally, pretreatment with MTP-PE dramatically reduced mortality; the average death rates for both series of animals used were 55% for liposome-pretreated animals and 3% for animals pretreated with MTP-PE-containing liposomes. These results in a preclinical model suggest that treatment with MTP-PE-containing liposomes might be beneficial in controlling septicemia in patients at risk.

Cross-reacting opsonic antibodies to clinically important pneumococcal serotypes after pneumococcal vaccination.

Opsonic activity of serum to pneumococcal serotypes 6 B, 9 V and 19 A was measured in 16 patients before and after immunization with a pneumococcal vaccine. The capsular polysaccharides of these serotypes are not included among, but are antigenically related to the vaccine polysaccharides. Patients responding to immunization with a twofold increase in serum antibodies to vaccine polysaccharides 6 A, 19 F and 23 F were studied. Increased opsonic activity towards serotypes 6 B, 9 V and 19 A was found in 12, four and ten patients respectively. In ten of the patients antibodies to serotypes 6 B, 9 V and 19 A were measured by a staphylococcal protein-A binding assay. A twofold increase in antibodies was found in postvaccination samples from ten, three and seven patients respectively. These results indicate that humans responding to pneumococcal vaccination, may also develop opsonic antibodies to other clinically important pneumococcal serotypes. The degree of cross-immunization appears to vary between individuals and between different pneumococcal serotypes.