ABSTRACT
BACKGROUND: Group A Neisseria meningitidis has been a major cause of bacterial meningitis in the sub-Saharan region of Africa in the meningitis belt. Neisseria meningitidis is an encapsulated pathogen, and antibodies against the capsular polysaccharide are protective. Polysaccharide-protein conjugate vaccines have proven to be highly effective against several different encapsulated bacterial pathogens. Purified polysaccharide vaccines have been used to control group A meningococcal (MenA) epidemics with minimal success. METHODS: A monovalent MenA polysaccharide-tetanus toxoid conjugate was therefore developed. This vaccine was developed by scientists working with the Meningitis Vaccine Project, a partnership between PATH and the World Health Organization. RESULTS: A high-efficiency conjugation method was developed in the Laboratory of Bacterial Polysaccharides in the Center for Biologics Evaluation and Research and transferred to the Serum Institute of India, Ltd, which then developed methods for purification of the group A polysaccharide and used its tetanus toxoid as the carrier protein to produce the now-licensed, highly effective MenAfriVac conjugate vaccine. CONCLUSIONS: Although many years of application of meningococcal polysaccharide vaccines have had minimal success in preventing meningococcal epidemics in the meningitis belt of Africa, our collaborative efforts to develop a MenA conjugate vaccine yielded a safe and highly effective vaccine.
Subject(s)
Disease Transmission, Infectious/prevention & control , Meningitis, Meningococcal/prevention & control , Meningococcal Vaccines/immunology , Meningococcal Vaccines/isolation & purification , Neisseria meningitidis, Serogroup A/immunology , Technology, Pharmaceutical/methods , Africa South of the Sahara/epidemiology , Humans , India , International Cooperation , Meningitis, Meningococcal/epidemiology , Meningitis, Meningococcal/microbiology , World Health OrganizationABSTRACT
Pathogenic Neisseria meningitidis isolates contain a polysaccharide capsule that is the main virulence determinant for this bacterium. Thirteen capsular polysaccharides have been described, and nuclear magnetic resonance spectroscopy has enabled determination of the structure of capsular polysaccharides responsible for serogroup specificity. Molecular mechanisms involved in N. meningitidis capsule biosynthesis have also been identified, and genes involved in this process and in cell surface translocation are clustered at a single chromosomal locus termed cps. The use of multiple names for some of the genes involved in capsule synthesis, combined with the need for rapid diagnosis of serogroups commonly associated with invasive meningococcal disease, prompted a requirement for a consistent approach to the nomenclature of capsule genes. In this report, a comprehensive description of all N. meningitidis serogroups is provided, along with a proposed nomenclature, which was presented at the 2012 XVIIIth International Pathogenic Neisseria Conference.
Subject(s)
Bacterial Capsules/genetics , Chromosomes, Bacterial , Genes, Bacterial , Neisseria meningitidis/genetics , Polysaccharides, Bacterial/genetics , Bacterial Capsules/metabolism , Genetic Loci , Humans , Magnetic Resonance Spectroscopy , Meningococcal Infections/microbiology , Multigene Family , Neisseria meningitidis/classification , Neisseria meningitidis/isolation & purification , Neisseria meningitidis/pathogenicity , Polymerase Chain Reaction , Polysaccharides, Bacterial/biosynthesis , Polysaccharides, Bacterial/isolation & purification , Serotyping , Terminology as Topic , VirulenceABSTRACT
Group A meningococcal disease has been an important public health problem in sub-Saharan Africa for over a century. Outbreaks occur there annually, and large epidemics occur at intervals ranging between 8 and 12 y. The Meningitis Vaccine Project was established in 2001 with funding from the Gates Foundation with the goal of developing, testing, licensing, and introducing an affordable group A meningococcal conjugate vaccine into Africa. From 2003 to 2009 a monovalent group A conjugate vaccine, MenAfriVac(TM) , was developed at the Serum Institute of India, Ltd through an innovative public/private partnership. Preclinical studies of the new conjugate vaccine were completed in 2004 and a Phase 1 study began in India in 2005. Phase 2/3 studies in African 1-29 y olds were completed in 2009 showing the new meningococcal A conjugate vaccine to be as safe as currently licensed meningococcal polysaccharide vaccines, but much more immunogenic. After Indian market authorization (December 2009) and WHO prequalification (June 2010), MenAfriVac(TM) was introduced at public health scale using a single 10 µg dose in individuals 1-29 y of age in Burkina Faso, Mali, and Niger in December 2010. We summarize the laboratory and clinical studies leading to prequalification of MenAfriVac(TM). The 2011 epidemic season ended with no reported case of group A meningitis in vaccinated individuals.
Subject(s)
Meningitis, Meningococcal/immunology , Meningococcal Vaccines/immunology , Vaccines, Conjugate/immunology , Vaccines, Conjugate/therapeutic use , Adolescent , Adult , Africa South of the Sahara/epidemiology , Child , Child, Preschool , Female , Humans , Infant , Male , Meningitis, Meningococcal/epidemiology , Meningitis, Meningococcal/prevention & control , Meningococcal Vaccines/therapeutic use , Molecular Structure , Young AdultABSTRACT
Capsular polysaccharide (CP) plays an important role in the pathogenicity and immunogenicity of Staphylococcus aureus, yet the common serotypes of S. aureus isolated from US pediatric patients have not been reported. We investigated capsular serotype as well as methicillin susceptibility, presence of Panton-Valentine leukocidin (PVL), and clonal relatedness of pediatric S. aureus isolates. Clinical isolates were tested for methicillin susceptibility, presence of mecA, lukS-PV and lukF-PV, cap5 and cap8 genes by PCR, and for capsular or surface polysaccharide expression (CP5, CP8, or 336 polysaccharide) by agglutination. Genetic relatedness was determined by pulsed-field gel electrophoresis. All S. aureus isolates encoded cap5 or cap8. Sixty-nine percent of 2004-2005 isolates were methicillin-susceptible (MSSA) and most expressed a detectable capsule. The majority of MRSA isolates (82%) were unencapsulated, exposing an expressed cell wall techoic acid antigen 336. Pulsed-field type USA300 were MRSA, PVL-positive, unencapsulated strains that were associated with deep skin infections and recurrent disease. Over half (58%) of all isolates from invasive pediatric dermatologic infections were USA300. All pediatric isolates contained either capsule type 5 or capsule type 8 genes, and roughly half of the S. aureus clinical disease isolates from our population were diverse MSSA-encapsulated strains. The majority of the remaining pediatric clinical disease isolates were unencapsulated serotype 336 strains of the PVL(+) USA300 community-associated-MRSA clone.
Subject(s)
Community-Acquired Infections/microbiology , Methicillin-Resistant Staphylococcus aureus/classification , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Staphylococcal Infections/microbiology , Adolescent , Bacterial Capsules/analysis , Bacterial Capsules/genetics , Bacterial Toxins/genetics , Child , Child, Preschool , Cluster Analysis , Exotoxins/genetics , Female , Genotype , Humans , Infant , Infant, Newborn , Leukocidins/genetics , Male , Methicillin-Resistant Staphylococcus aureus/chemistry , Methicillin-Resistant Staphylococcus aureus/genetics , Microbial Sensitivity Tests , Molecular Typing , United StatesABSTRACT
The history of the pneumococcal polysaccharide enzyme-linked immunosorbent assay (ELISA) is characterized by a continuous search for increased specificity. A third-generation ELISA that uses 22F polysaccharide inhibition has increased the specificity of the assay, particularly at low antibody concentrations. The present work compared various 22F ELISAs and non-22F ELISAs. The comparisons involved three different laboratories, including a WHO reference laboratory, and included sera from subjects from different geographic areas immunized with different pneumococcal conjugate vaccines, including the licensed 7-valent Prevenar vaccine and the 10-valent Synflorix vaccine. All comparisons led to the same conclusion that the threshold defined as 0.35 microg/ml for the WHO non-22F ELISA is lower when any 22F ELISA is used. The use of highly purified polysaccharides for coating further improved the specificity of the assay. In conclusion, we confirm that the 22F ELISA can be recommended as a reference method for the determination of antibodies against pneumococcal polysaccharides.
Subject(s)
Antibodies, Bacterial/blood , Enzyme-Linked Immunosorbent Assay/methods , Pneumococcal Vaccines/immunology , Polysaccharides, Bacterial/immunology , Adsorption , Humans , Infant , Sensitivity and Specificity , Vaccines, Conjugate/immunologyABSTRACT
A conjugate can be a polysaccharide (PS) covalently attached to a protein, which provides T cell epitopes for a normally T cell independent antigen. To produce a conjugate vaccine, the purified PS must first be chemically modified to generate reactive groups that can link to the protein. Two commonly used methods for PS activation are periodate oxidation at vicinal hydroxyls and cyanylation of hydroxyls. The PS should be of known molecular size before and after activation. Low molecular weight impurities in the protein may result in inefficient conjugation. Two critical measures after conjugation and purification are the PS to protein ratio and the percent non-conjugated saccharide (free saccharide). Yield and conjugate stability are critical considerations. Typically, considerably less than 20% of the activated PS becomes conjugated. Yield can be improved using newer conjugation methods, whereby highly reactive groups are generated on both the PS and carrier protein with yields approaching 50%. Two major measures used to follow vaccine stability are changes in molecular size and percent free (unbound) PS.
Subject(s)
Bacterial Proteins/biosynthesis , Polysaccharides, Bacterial/biosynthesis , Technology, Pharmaceutical/methods , Vaccines, Conjugate/biosynthesis , Bacterial Proteins/immunology , Polysaccharides, Bacterial/immunology , Quality Control , Vaccines, Conjugate/immunologyABSTRACT
It has been demonstrated that antibodies induced by meningococcal polysaccharide, polysaccharide-protein conjugates and outer membrane protein vaccines protect against meningococcal disease. This review will show that the induced antibody protects via complement mediated bactericidal killing and that induction of serum bactericidal antibody (SBA) is a good surrogate for efficacy. The critical role of SBA is shown by: (1) Highest incidence of meningococcal disease occurs in infants between 6 and 18 months of age, who have the lowest levels of SBA. (2) Studies published in 1969 in US Army recruits showed a direct correlation between susceptibility to meningococcal disease and absence of SBA. (3) Meningococcal polysaccharide, polysaccharide-protein conjugates, and outer membrane vesicle vaccines all induce SBA shown to be effective in direct proportion to the percent of vaccinees with SBA activity.
Subject(s)
Antibodies, Bacterial/immunology , Blood Bactericidal Activity , Meningococcal Infections/prevention & control , Meningococcal Vaccines/immunology , Microbial Viability , Neisseria meningitidis/immunology , Neisseria meningitidis/physiology , Antibodies, Bacterial/blood , Complement System Proteins/immunology , HumansABSTRACT
Periodic epidemics of group A meningococcal (Mn A) meningitis continue to occur in sub-Saharan Africa. For its prevention, a Mn A polysaccharide (PS)-tetanus toxoid (TT) conjugate vaccine was developed using reductive amination of polysaccharide aldehydes and toxoid hydrazides. In mouse immunization studies, a schedule of three bi-weekly s.c. immunizations of 0.1 or 1mug of the conjugate (PS content) without an adjuvant induced serum antibody levels of >10,000units/mL measured by enzyme-linked immunosorbent assay (ELISA) as compared to approximately 100units/mL in PS control mice. The elicited antibodies were active in bactericidal assays using either baby rabbit or human complement (titers >1500 compared to approximately 200 for the PS control group). The synthesis process is reproducible and scalable, and has been successfully used for manufacturing a Mn A PS-TT conjugate vaccine based on a paradigm of shared manufacturing with transfer of new technology [Jodar L, LaForce FM, Ceccarini C, Aguado T, Granoff DM. Meningococcal conjugate vaccine for Africa: a model for development of new vaccine for the poorest countries. Lancet 2003, 361:1092-4]. A phase 1 clinical trial of the manufactured Men A-TT conjugate vaccine has been successfully carried out in adults in India, and a phase 2 clinical trial in young children is currently underway in Africa.
Subject(s)
Meningitis, Meningococcal/prevention & control , Meningococcal Vaccines/immunology , Neisseria meningitidis, Serogroup A/immunology , Adult , Africa , Animals , Antibodies, Bacterial/blood , Antibodies, Bacterial/immunology , Enzyme-Linked Immunosorbent Assay , Humans , Immunization, Secondary , India , Injections, Subcutaneous , Meningococcal Vaccines/administration & dosage , Mice , Microbial Viability , Tetanus Toxoid/administration & dosage , Tetanus Toxoid/immunology , Vaccines, Combined/administration & dosage , Vaccines, Combined/immunology , Vaccines, Conjugate/administration & dosageABSTRACT
Polysaccharide (PS) and tetanus toxoid (TT) protein conjugate vaccines were prepared using O-acetylated (OAc+), O-acetyl negative (OAc(-)) and chemically de-O-acetylated (de-OAc) meningococcal W135 PS. The PSs were activated by periodate oxidation and coupled to hydrazine derivatized TT. High performance anion exchange chromatography of acid hydrolysates of periodate activated W135 PSs, showed that galactose residues in OAc+ PS were more sensitive to the periodate oxidation step than they were in the OAc(-) PS or de-OAc PS. Mouse antisera against OAc(-)-TT conjugate vaccines recognized both OAc(-) and OAc+ PS by ELISAs and had high bactericidal titers against both OAc+ and OAc(-) W135 strains. Purified high molecular weight (HMW) conjugates showed higher PS to protein ratios in OAc(-)-TT(HMW) and de-OAc-TT(HMW) indicating better conjugation efficiency than OAc+-TT(HMW) conjugate. Antisera against the HMW fractions gave higher bactericidal titers than antisera against unfractionated conjugates. Inhibition ELISAs indicated that OAc(-) and OAc+ HMW conjugates induced antibodies that bound both OAc+ and OAc(-) PS. Thus, for W135, PS O-acetylation does not contribute a dominant immunogenic epitope. The OAc(-) PS may be a good starting material for preparing W135 PS-TT conjugate vaccines using periodate oxidation.
Subject(s)
Bacterial Vaccines/immunology , Neisseria meningitidis, Serogroup W-135/immunology , Polysaccharides, Bacterial/immunology , Tetanus Toxoid/immunology , Acetylation , Animals , Antibodies, Bacterial/immunology , Bacterial Vaccines/chemistry , Blood Bactericidal Activity/immunology , Enzyme-Linked Immunosorbent Assay , Epitopes/chemistry , Epitopes/immunology , Female , Hydrolysis , Meningococcal Infections/immunology , Meningococcal Infections/prevention & control , Mice , Neisseria meningitidis, Serogroup W-135/chemistry , Oxidation-Reduction , Periodic Acid , Polysaccharides, Bacterial/chemistry , Tetanus Toxoid/chemistry , Vaccines, Conjugate/chemistry , Vaccines, Conjugate/immunologyABSTRACT
This study compares the phylogenetic lineages of invasive serotype III group B streptococci (GBS) to those of colonizing strains in order to determine lineages associated with invasive disease. Isolates from 29 infants with early-onset disease (EOD) and from 196 colonized infants, collected in a prospective, multicenter study, were assigned a sequence type (ST) by multilocus sequence typing. Overall, 54.5% of the isolates were in the ST-19 complex, and 40.4% were in the ST-17 complex. Invasive strains were more likely to be in the ST-17 complex than were colonizing strains (59% versus 38%, P = 0.03). After we adjusted for potential confounders, the ST-17 complex was more likely to be associated with EOD than were other lineages (odds ratio = 2.51, 95% confidence interval = 1.02 to 6.20). These data support the hypothesis that ST-17 complex GBS are more virulent than other serotype III GBS.
Subject(s)
Antibodies, Bacterial/blood , Streptococcal Infections/epidemiology , Streptococcus agalactiae/classification , Streptococcus agalactiae/pathogenicity , Adult , Bacterial Typing Techniques/methods , Female , Humans , Infant, Newborn , Male , Phylogeny , Prospective Studies , Serotyping , Streptococcal Infections/immunology , Streptococcal Infections/transmission , Streptococcus agalactiae/geneticsABSTRACT
The generation and maintenance of memory antibody response by different primary immunization schedules with the Cuban-produced outer membrane protein based vaccine was investigated in a murine model. We analyzed the duration of the antibody response (IgG-ELISA and bactericidal titer) and the effect of a booster dose on the antibody response. The IgG avidity index was determined in an attempt to find a marker for memory development. This study also included an analysis of IgG subclasses induced by primary and booster immunization. The specificity of bactericidal antibodies was investigated using local strains of the same serotype/serosubtype (4,7:P1.19,15) as the vaccine strain and mutant strains lacking major outer membrane proteins. A significant recall response was induced by a booster dose given 7 months after a primary series of 2, 3 or 4 doses of vaccine. The primary antibody response showed a positive dose-effect. In contrast, a negative dose-effect was found on the booster bactericidal antibody response. There was a significant increase in IgG1 levels after the fourth and booster doses. Three doses of vaccine were required to induce a significant increase in IgG avidity. Two injections of vaccine induced a significant antibody response to PorA protein, while 4 injections induced a larger range of specificities.
Subject(s)
Antibodies, Bacterial/biosynthesis , Meningococcal Vaccines/administration & dosage , Neisseria meningitidis/immunology , Animals , Antibodies, Bacterial/blood , Antibody Affinity , Bacterial Outer Membrane Proteins/immunology , Blood Bactericidal Activity , Female , Immunization Schedule , Immunization, Secondary , Immunoglobulin G/biosynthesis , Immunoglobulin G/blood , Immunoglobulin G/classification , Immunologic Memory , Kinetics , MiceABSTRACT
Meningococcal disease, both endemic and epidemic, remains a major cause of meningitis in many countries. Protective immunity is mediated primarily by bacteriocidal antibodies against the capsular polysaccharides for serogroups other than B, and against non-capsular surface components for group B. This article focuses on the development of conjugate vaccines for serogroup A, with special emphasis on the needs of Africa. The first licensed (1999) meningococcal conjugate was against group C in the UK and was > 90% effective in infants, children and young adults. The problem now is to develop a highly immunogenic group A meningococcal conjugate vaccine for use in developing countries as an alternative to the presently licensed group AC polysaccharide vaccine. Immunogenicity studies on the group A polysaccharide show the polysaccharide itself to be uniquely immunogenic in young children compared with other polysaccharides, making comparative studies with a highly immunogenic conjugate of considerable importance.
Subject(s)
Meningitis, Meningococcal/prevention & control , Meningococcal Vaccines/therapeutic use , Neisseria meningitidis, Serogroup A , Technology, Pharmaceutical/trends , Animals , Humans , Meningitis, Meningococcal/epidemiology , Meningococcal Vaccines/chemical synthesis , Vaccines, Conjugate/chemistry , Vaccines, Conjugate/therapeutic useABSTRACT
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.
Subject(s)
Bacterial Capsules/immunology , Haemophilus influenzae type b/immunology , Immunoglobulins, Intravenous/analysis , Streptococcus pneumoniae/immunology , Haemophilus Infections/drug therapy , Humans , Immunoglobulin G/analysis , Immunoglobulin G/immunology , Immunoglobulins, Intravenous/immunology , Immunoglobulins, Intravenous/therapeutic use , Immunologic Deficiency Syndromes/complications , Immunologic Deficiency Syndromes/drug therapy , Pneumococcal Infections/drug therapy , Quality ControlABSTRACT
The present study estimates the level of maternal immunoglobulin (Ig) G anti-group B streptococcus (GBS) type III required to protect neonates against early-onset disease (EOD) caused by this pathogen. Levels of maternal serum IgG anti-GBS type III, measured by enzyme-linked immunosorbent assay, in 26 case patients (neonates with EOD caused by GBS type III) and 143 matched control subjects (neonates colonized by GBS type III who did not develop EOD) of > or = 34 weeks gestation were compared. The probability of EOD decreased with increasing levels of maternal IgG anti-GBS type III (P = .01). Neonates whose mothers had > or = 10 microg/mL IgG anti-GBS type III had a 91% lower risk for EOD, compared with those whose mothers had levels of < 2 microg/mL. A vaccine that induces IgG anti-GBS type III levels of > or = 10 microg/mL in mothers can be predicted to offer a significant degree of protection against EOD caused by this pathogen.
Subject(s)
Antibodies, Bacterial/blood , Immunity, Maternally-Acquired , Immunoglobulin G/blood , Infant, Premature, Diseases/immunology , Streptococcal Infections/immunology , Streptococcus agalactiae/immunology , Age of Onset , Antibodies, Bacterial/immunology , Antibody Specificity , Case-Control Studies , Female , Fetal Blood/immunology , Humans , Immunoglobulin G/immunology , Infant, Newborn , Infant, Premature , Infant, Premature, Diseases/prevention & control , Pregnancy , Pregnancy Complications, Infectious/immunology , Streptococcal Infections/prevention & controlABSTRACT
Neisseria meningitidis (N. meningitidis) is a serious bacterial pathogen that causes life-threatening invasive bacterial infections especially in children below 2 years of age, teenagers and young adults. We have investigated the protective potential of outer membrane vesicles (OMVs) and detoxified lipooligosaccharide (dLOS) obtained from Brazilian prevalent N. meningitidis serogroup B strains. Swiss mice were immunized with different combinations of OMV and dLOS from N. meningitidis serogroup B strains compared to a reference vaccine (VA-MENGOC-BC), Cuba). The OMVs + dLOS from Brazilian prevalent strains induced higher bactericidal antibody titers against homologous and heterologous target strains and stronger inhibition of thrombocytopenia as compared to the reference vaccine. When the challenge was performed with the B strain, all immunogens tested showed similar survival rates (80%) significantly higher than the control group. Bacterial clearance against the group B strain was comparable for animals immunized with the tested immunogen and the reference vaccine. Inclusion of dLOS from the B strain with the OMV, induced a similar clearance of C strain bacteria as compared to VA-MENGOC-BC. The immunogens, as well as the reference vaccine drastically inhibited increases in TNF-alpha and IL-6 plasma levels after challenge. In conclusion, the OMV/dLOS formulation obtained from Brazilian prevalent strains of N. meningitidis has a remarkable performance protecting mice against the lethal effects of meningococcal challenge showing a good potential as a vaccine and should be considered for clinical evaluation.
Subject(s)
Antibodies, Bacterial/biosynthesis , Bacterial Outer Membrane Proteins/immunology , Lipopolysaccharides/administration & dosage , Meningococcal Infections/prevention & control , Neisseria meningitidis/immunology , Shock, Septic/prevention & control , Animals , Bacterial Outer Membrane Proteins/administration & dosage , Bacterial Outer Membrane Proteins/analysis , Bacterial Vaccines , Brazil , Cytokines/blood , Lipopolysaccharides/immunology , Meningococcal Infections/immunology , Mice , Shock, Septic/immunologyABSTRACT
Pneumococcal polysaccharides (PSs), designated as T-cell independent type 2 (TI-2) antigens, induce poor immune responses in young children. Splenic marginal zone B cells, associated with CD21, CD19 and C3d, play an important role in TI-2 antibody responses, and provide host defense against bacterial pathogens. Antibody response, avidity, and opsonophagocytic activity of antisera were examined in mice immunized with type 9V PS conjugated to inactivated pneulmolysin (Ply) or to autolysin (Aly). Compared to mice given 9V PS alone, serum IgG and IgM concentrations against the 9V PS were higher in mice immunized with conjugates. High concentrations of serum antibodies were maintained for over 12 weeks. The relative avidities of IgG and IgM antibodies and opsonophagocytic activity against 9V pneumococci were high in mice immunized with conjugates. Thus, conjugate vaccines can induce high as well as long duration of antibody response and effective functional activity. In another study, mice received intranasal immunization with type 9V conjugate or 9V PS. These animals produced 9V PS IgG and IgA antibodies in their serum, spleen, intestine, lung, Peyer's patch and fecal extract samples. Mice immunized with these glycoconjugates exhibited opsonophagocytic activity and rapid bacterial clearance from blood and provided homologous and cross-protection against challenge with virulent pneumococci. These results indicate that intranasal immunization with glycoconjugate vaccines may serve as an alternative and convenient approach for prevention of pneumococcal infection.
Subject(s)
Antibodies, Bacterial/blood , Glycoconjugates/immunology , Pneumococcal Infections/prevention & control , Pneumococcal Vaccines/immunology , Polysaccharides, Bacterial/immunology , Streptococcus pneumoniae/immunology , Animals , Carrier Proteins/immunology , Humans , Mice , Pneumococcal Infections/immunology , Pneumococcal Vaccines/administration & dosage , Vaccines, Conjugate/administration & dosage , Vaccines, Conjugate/immunologySubject(s)
Antibodies, Bacterial/analysis , Enzyme-Linked Immunosorbent Assay , Pneumococcal Vaccines/immunology , Polysaccharides, Bacterial/immunology , Streptococcus pneumoniae/immunology , Antibodies, Bacterial/immunology , Enzyme-Linked Immunosorbent Assay/methods , Enzyme-Linked Immunosorbent Assay/standards , Enzyme-Linked Immunosorbent Assay/trends , Humans , Immunoglobulin G/analysis , Immunoglobulin G/immunology , Indicators and Reagents , Pneumococcal Vaccines/standards , Radioimmunoassay , Reproducibility of Results , Sensitivity and Specificity , World Health OrganizationABSTRACT
The purpose of the NIAID/FDA joint workshop, "correlates of immunity for pneumococcal conjugate vaccines (PCVs)," was to discuss the present understanding of protective immunity against invasive pneumococcal disease and identify in vitro measures that may represent immunologic correlates in future clinical trials. Animal and clinical data support functional antibody as the basis for protection, but IgG antibody concentration has conventionally been the principle immunologic parameter for non-inferiority comparisons. No consensus for a pre-defined threshold antibody level was reached. Affinity maturation may contribute to protection, but its role has not been established. Opsonophagocytic activity, avidity and immunologic memory are important secondary measures to characterise functional antibody and long-term protective responses. Immunologic memory may also be useful for evaluation of new vaccine serotypes. More definitive qualitative and quantitative immunogenicity criteria for use by National Control Authorities still need to be established.
Subject(s)
Meningitis, Pneumococcal/immunology , Pneumococcal Vaccines/immunology , Vaccines, Conjugate/immunology , Antibodies, Bacterial/blood , Antibody Formation , Humans , Reproducibility of ResultsABSTRACT
The epidemiology of invasive Streptococcus agalactiae (GBS) disease was evaluated in South African children. Records of 208/220 children in whom GBS was isolated between January 1997 and December 1999 were reviewed. These included 63%, 31.7% and 5.3% children with early- (EOD, <7 days of age), late- (LOD, age 7-90 days) and childhood-onset disease (COD, age >90 days), respectively. The overall burden of EOD and LOD were 2.06 and 1/1000 live births, respectively. The overall mortality was 19.8% and 13.6% for infants with EOD and LOD, respectively. Risk factors for mortality in infants with EOD and LOD included septic shock (82.1% vs 1.9%), prematurity (35.2% vs 9.6%), low birthweight (29.2% vs 11.0%) and a leucocyte count <5000/mm(3) (43.5% vs 18.6%). Eight (72.7%) of 11 children with COD had an immunosuppressive, predisposing cause for invasive bacterial disease. In infants with EOD and LOD, serotype III isolates caused 49.2% and 75.7% of disease, respectively, and, together with serotype Ia isolates, caused 78.9% and 100% of invasive disease, respectively. Invasive GBS disease is common in South African infants and current strategies aimed at reducing the burden of the disease should be reconsidered.