PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-15 (15)
 

Clipboard (0)
None

Select a Filter Below

Journals
Year of Publication
more »
Document Types
1.  Pneumococcal Polysaccharide Abrogates Conjugate-Induced Germinal Center Reaction and Depletes Antibody Secreting Cell Pool, Causing Hyporesponsiveness 
PLoS ONE  2013;8(9):e72588.
Background
Plain pneumococcal polysaccharide (PPS) booster administered during second year of life has been shown to cause hyporesponsiveness. We assessed the effects of PPS booster on splenic memory B cell responses and persistence of PPS-specific long-lived plasma cells in the bone marrow (BM).
Methods
Neonatal mice were primed subcutanously (s.c.) or intranasally (i.n.) with pneumococcal conjugate (Pnc1-TT) and the adjuvant LT-K63, and boosted with PPS+LT-K63 or saline 1, 2 or 3 times with 16 day intervals. Seven days after each booster, spleens were removed, germinal centers (GC), IgM+, IgG+ follicles and PPS-specific antibody secreting cells (AbSC) in spleen and BM enumerated.
Results
PPS booster s.c., but not i.n., compromised the Pnc1-TT-induced PPS-specific Abs by abrogating the Pnc1-TT-induced GC reaction and depleting PPS-specific AbSCs in spleen and limiting their homing to the BM. There was no difference in the frequency of PPS-specific AbSCs in spleen and BM between mice that received 1, 2 or 3 PPS boosters s.c.. Repeated PPS+LT-K63 booster i.n. reduced the frequency of PPS-specific IgG+ AbSCs in BM.
Conclusions
PPS booster-induced hyporesponsiveness is caused by abrogation of conjugate-induced GC reaction and depletion of PPS-specific IgG+ AbSCs resulting in no homing of new PPS-specific long-lived plasma cells to the BM or survival. These results should be taken into account in design of vaccination schedules where polysaccharides are being considered.
doi:10.1371/journal.pone.0072588
PMCID: PMC3771989  PMID: 24069152
2.  Variant of TREM2 Associated with the Risk of Alzheimer’s Disease 
The New England journal of medicine  2012;368(2):107-116.
BACKGROUND
Sequence variants, including the ε4 allele of apolipoprotein E, have been associated with the risk of the common late-onset form of Alzheimer’s disease. Few rare variants affecting the risk of late-onset Alzheimer’s disease have been found.
METHODS
We obtained the genome sequences of 2261 Icelanders and identified sequence variants that were likely to affect protein function. We imputed these variants into the genomes of patients with Alzheimer’s disease and control participants and then tested for an association with Alzheimer’s disease. We performed replication tests using case–control series from the United States, Norway, the Netherlands, and Germany. We also tested for a genetic association with cognitive function in a population of unaffected elderly persons.
RESULTS
A rare missense mutation (rs75932628-T) in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2), which was predicted to result in an R47H substitution, was found to confer a significant risk of Alzheimer’s disease in Iceland (odds ratio, 2.92; 95% confidence interval [CI], 2.09 to 4.09; P = 3.42×10−10). The mutation had a frequency of 0.46% in controls 85 years of age or older. We observed the association in additional sample sets (odds ratio, 2.90; 95% CI, 2.16 to 3.91; P = 2.1×10−12 in combined discovery and replication samples). We also found that carriers of rs75932628-T between the ages of 80 and 100 years without Alzheimer’s disease had poorer cognitive function than noncarriers (P = 0.003).
CONCLUSIONS
Our findings strongly implicate variant TREM2 in the pathogenesis of Alzheimer’s disease. Given the reported antiinflammatory role of TREM2 in the brain, the R47H substitution may lead to an increased predisposition to Alzheimer’s disease through impaired containment of inflammatory processes. (Funded by the National Institute on Aging and others.)
doi:10.1056/NEJMoa1211103
PMCID: PMC3677583  PMID: 23150908
3.  Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22 
Evangelou, Evangelos | Valdes, Ana M. | Kerkhof, Hanneke J.M | Styrkarsdottir, Unnur | Zhu, YanYan | Meulenbelt, Ingrid | Lories, Rik J. | Karassa, Fotini B. | Tylzanowski, Przemko | Bos, Steffan D. | Akune, Toru | Arden, Nigel K. | Carr, Andrew | Chapman, Kay | Cupples, L. Adrienne | Dai, Jin | Deloukas, Panos | Doherty, Michael | Doherty, Sally | Engstrom, Gunnar | Gonzalez, Antonio | Halldorsson, Bjarni V. | Hammond, Christina L. | Hart, Deborah J. | Helgadottir, Hafdis | Hofman, Albert | Ikegawa, Shiro | Ingvarsson, Thorvaldur | Jiang, Qing | Jonsson, Helgi | Kaprio, Jaakko | Kawaguchi, Hiroshi | Kisand, Kalle | Kloppenburg, Margreet | Kujala, Urho M. | Lohmander, L. Stefan | Loughlin, John | Luyten, Frank P. | Mabuchi, Akihiko | McCaskie, Andrew | Nakajima, Masahiro | Nilsson, Peter M. | Nishida, Nao | Ollier, William E.R. | Panoutsopoulou, Kalliope | van de Putte, Tom | Ralston, Stuart H. | Rivadeneira, Fernado | Saarela, Janna | Schulte-Merker, Stefan | Slagboom, P. Eline | Sudo, Akihiro | Tamm, Agu | Tamm, Ann | Thorleifsson, Gudmar | Thorsteinsdottir, Unnur | Tsezou, Aspasia | Wallis, Gillian A. | Wilkinson, J. Mark | Yoshimura, Noriko | Zeggini, Eleftheria | Zhai, Guangju | Zhang, Feng | Jonsdottir, Ingileif | Uitterlinden, Andre G. | Felson, David T | van Meurs, Joyce B. | Stefansson, Kari | Ioannidis, John P.A. | Spector, Timothy D.
Annals of the rheumatic diseases  2010;70(2):349-355.
Osteoarthritis (OA) is the most prevalent form of arthritis and accounts for substantial morbidity and disability, particularly in the elderly. It is characterized by changes in joint structure including degeneration of the articular cartilage and its etiology is multifactorial with a strong postulated genetic component. We performed a meta-analysis of four genome-wide association (GWA) studies of 2,371 knee OA cases and 35,909 controls in Caucasian populations. Replication of the top hits was attempted with data from additional ten replication datasets. With a cumulative sample size of 6,709 cases and 44,439 controls, we identified one genome-wide significant locus on chromosome 7q22 for knee OA (rs4730250, p-value=9.2×10−9), thereby confirming its role as a susceptibility locus for OA. The associated signal is located within a large (500kb) linkage disequilibrium (LD) block that contains six genes; PRKAR2B (protein kinase, cAMP-dependent, regulatory, type II, beta), HPB1 (HMG-box transcription factor 1), COG5 (component of oligomeric golgi complex 5), GPR22 (G protein-coupled receptor 22), DUS4L (dihydrouridine synthase 4-like), and BCAP29 (the B-cell receptor-associated protein 29). Gene expression analyses of the (six) genes in primary cells derived from different joint tissues confirmed expression of all the genes in the joint environment.
doi:10.1136/ard.2010.132787
PMCID: PMC3615180  PMID: 21068099
4.  The Adjuvant LT-K63 Can Restore Delayed Maturation of Follicular Dendritic Cells and Poor Persistence of Both Protein- and Polysaccharide-Specific Antibody-Secreting Cells in Neonatal Mice 
Ab responses in early life are low and short-lived; therefore, induction of protective immunity requires repeated vaccinations. One of the major limitations in early-life immunity is delayed maturation of follicular dendritic cells (FDCs), which play a central role in mediating the germinal center (GC) reaction leading to production of Ab-secreting cells (AbSCs). We assessed whether a nontoxic mutant of Escherichia coli heat-labile enterotoxin (LT-K63) and CpG1826 as model adjuvants could accelerate FDC maturation and immune response in neonatal mice, using a pneumococcal polysaccharide of serotype 1 conjugated to tetanus toxoid (Pnc1-TT) as a model vaccine. In neonatal NMRI mice, a single dose of Pnc1-TT coadministered with LT-K63 enhanced Pnc1-TT–induced GC reaction. In contrast, CpG1826 had no effect. Accordingly, LT-K63, but not CpG1826, accelerated the maturation of FDC networks, detected by FDC-M2+ staining, characteristic for adult-like FDCs. This coincided with migration of MOMA-1+ macrophages into the GCs that can enhance GC reaction and B cell activation. The FDC-M2+ FDC networks colocalized with enhanced expression of TNF-α, which is critical for the maintenance of mature FDCs and is poorly expressed in neonates. The accelerated maturation of FDC networks correlated with increased frequency and prolonged persistence of polysaccharide- and protein-specific IgG+ AbSCs in spleen and bone marrow. Our data show for the first time, to our knowledge, that an adjuvant (LT-K63) can overcome delayed maturation of FDCs in neonates, enhance the GC reaction, and prolong the persistence of vaccine-specific AbSCs in the BM. These properties are attractive for parenteral vaccination in early life.
doi:10.4049/jimmunol.1200761
PMCID: PMC3496199  PMID: 22753937
5.  Novel Protein-Based Pneumococcal Vaccines Administered with the Th1-Promoting Adjuvant IC31 Induce Protective Immunity against Pneumococcal Disease in Neonatal Mice 
Infection and Immunity  2012;80(1):461-468.
Streptococcus pneumoniae is responsible for many vaccine-preventable deaths, annually causing around 1 million deaths in children younger than 5 years of age. A new generation of pneumococcal vaccines based on conserved proteins is being developed. We evaluated the immunogenicities and protective efficacies of four pneumococcal protein vaccine candidates, PcsB, StkP, PsaA, and PspA, in a neonatal mouse model. Mice were immunized three times and challenged intranasally with virulent pneumococci. All four proteins were immunogenic in neonatal mice, and antibody (Ab) responses were significantly enhanced by the novel adjuvant IC31, which consists of an antibacterial peptide (KLKL5KLK) and a synthetic oligodeoxynucleotide, ODN1a, that signals through Toll-like receptor 9 (TLR9). Two single proteins, StkP and PspA, combined with IC31 significantly reduced pneumococcal bacteremia but had no effects on lung infection. Three proteins, PcsB, StkP, and PsaA, were evaluated with alum or IC31. IC31 enhanced Ab responses and avidity to all three proteins, whereas alum enhanced Ab responses and avidity to StkP and PsaA only. Mice receiving the trivalent protein formulation with IC31 had significantly reduced bacteremia and lung infection compared to unvaccinated mice, but the level of protection was dependent on the dose of IC31. When PspA was added to the trivalent protein formulation, the dose of IC31 needed to obtain protective immunity could be reduced. These results demonstrate that a novel pneumococcal protein-based vaccine is immunogenic at an early age of mice and emphasize the benefits of using a combination of conserved proteins and an effective adjuvant to elicit potent protective immunity against invasive pneumococcal disease.
doi:10.1128/IAI.05801-11
PMCID: PMC3255653  PMID: 22025519
6.  A Genome-Wide Association Study identifies a locus on chromosome 7q22 to influence susceptibility for osteoarthritis 
Arthritis and Rheumatism  2010;62(2):499-510.
To identify genes involved in osteoarthritis (OA), the most prevalent form of joint disease, we performed a genome-wide association study (GWAS) in which we tested 500,510 Single Nucelotide Polymorphisms (SNPs) in 1341 OA cases and 3496 Dutch Caucasian controls. SNPs associated with at least two OA-phenotypes were analysed in 14,938 OA cases and approximately 39,000 controls. The C-allele of rs3815148 on chromosome 7q22 (MAF 23%, 172 kb upstream of the GPR22 gene) was consistently associated with a 1.14-fold increased risk (95%CI: 1.09–1.19) for knee- and/or hand-OA (p=8×10−8), and also with a 30% increased risk for knee-OA progression (95%CI: 1.03–1.64, p=0.03). This SNP is in almost complete linkage disequilibrium with rs3757713 (located 68 kb upstream of GPR22) which is associated with GPR22 expression levels in lymphoblast cell lines (p=4×10−12). GPR22 encodes an G-protein coupled receptor with unkown ligand (orphan receptor). Immunohistochemistry experiments showed absence of GPR22 in normal mouse articular cartilage or synovium. However, GPR22 positive chondrocytes were found in the upper layers of the articular cartilage of mouse knee joints that were challenged by in vivo papain treatment or in the presence of interleukin-1 driven inflammation. GRP22 positive chondrocyte-like cells were also found in osteophytes in instability-induced OA. In addition, GPR22 is also present in areas of the brain involved in locomotor function. Our findings reveal a novel common variant on chromosome 7q22 to influence susceptibility for prevalence and progression of OA.
doi:10.1002/art.27184
PMCID: PMC3354739  PMID: 20112360
7.  Concomitant Administration of Mycobacterium bovis BCG with the Meningococcal C Conjugate Vaccine to Neonatal Mice Enhances Antibody Response and Protective Efficacy ▿ 
Clinical and Vaccine Immunology : CVI  2011;18(11):1936-1942.
Mycobacterium bovis BCG is administered to human neonates in many countries worldwide. The objective of the study was to assess if BCG could act as an adjuvant for polysaccharide-protein conjugate vaccines in newborns and thereby induce protective immunity against encapsulated bacteria in early infancy when susceptibility is high. We assessed whether BCG could enhance immune responses to a meningococcal C (MenC) conjugate vaccine, MenC-CRM197, in mice primed as neonates, broaden the antibody response from a dominant IgG1 toward a mixed IgG1 and IgG2a/IgG2b response, and increase protective efficacy, as measured by serum bactericidal activity (SBA). Two-week-old mice were primed subcutaneously (s.c.) with MenC-CRM197. BCG was administered concomitantly, a day or a week before MenC-CRM197. An adjuvant effect of BCG was observed only when it was given concomitantly with MenC-CRM197, with increased IgG response (P = 0.002) and SBA (8-fold) after a second immunization with MenC-CRM197 without BCG, indicating increased T-cell help. In neonatal mice (1 week old) primed s.c. with MenC-CRM197 together with BCG, MenC-polysaccharide (PS)-specific IgG was enhanced compared to MenC-CRM197 alone (P = 0.0015). Sixteen days after the second immunization with MenC-CRM197, increased IgG (P < 0.05), IgG1 (P < 0.05), IgG2a (P = 0.06), and IgG2b (P < 0.05) were observed, and only mice primed with MenC-CRM197 plus BCG showed affinity maturation and detectable SBA (SBA > 128). Thus, vaccination with a meningococcal conjugate vaccine (and possibly with other conjugates) may benefit from concomitant administration of BCG in the neonatal period to accelerate and enhance production of protective antibodies, compared to the current infant administration of conjugate which follows BCG vaccination at birth.
doi:10.1128/CVI.05247-11
PMCID: PMC3209029  PMID: 21900528
8.  Protective Levels of Polysaccharide-Specific Maternal Antibodies May Enhance the Immune Response Elicited by Pneumococcal Conjugates in Neonatal and Infant Mice  
Infection and Immunity  2005;73(2):956-964.
Maternal antibodies (MatAbs) may protect the offspring against infections but may also interfere with their immune responses to vaccination. We have previously shown that maternal immunization with pneumococcal polysaccharides (PPS) conjugated to tetanus protein (Pnc-TT) protected the offspring against infections caused by three important pediatric serotypes. To study the influence of MatAb on the immune response to Pnc-TT early in life, adult female mice were immunized twice with Pnc-TT of serotype 1 (Pnc1-TT), and their offspring received Pnc1-TT subcutaneously three times at 3-week intervals starting at 1 week (neonatal) or 3 weeks (infant) of age. High levels of PPS-1-specific MatAb (>3 log) in offspring of Pnc1-TT-immunized dams completely inhibited their anti-PPS-1 response elicited by Pnc1-TT. In contrast, low or moderate (∼1 to 2 log) levels of MatAb did not interfere with and even enhanced the immune response of the offspring, and a booster response to a second Pnc1-TT dose was observed. Carrier-specific MatAbs had little effect on the response of offspring to the conjugate. All Pnc1-TT-immunized offspring were protected against pneumococcal bacteremia and had reduced lung infection. These results demonstrate that in the presence of MatAb, Pnc1-TT may elicit a protective PPS-1-specific antibody response and prime for PPS-1-specific memory in young offspring. Importantly, low or moderate levels of PPS-1-specific MatAb not only provided protection against pneumococcal infections but also enhanced the immune response elicited by Pnc1-TT in neonatal and infant mice. This murine model will be used to develop novel strategies combining maternal and neonatal immunization to protect against infections caused by encapsulated bacteria in early life.
doi:10.1128/IAI.73.2.956-964.2005
PMCID: PMC546934  PMID: 15664938
9.  Immunization of Female Mice with Glycoconjugates Protects Their Offspring against Encapsulated Bacteria  
Infection and Immunity  2004;72(1):187-195.
The immune system of the newborn is immature, and therefore it is difficult to induce protective immunity by vaccination in the neonatal period. Immunization of mothers during pregnancy against infections caused by encapsulated bacteria could thus be particularly attractive, as infants do not respond to polysaccharide (PS) antigens. Transmission of maternal vaccine-specific antibodies and protection of offspring against pneumococcal bacteremia and/or lung infection were studied in a neonatal murine model of pneumococcal immunization and infections. Adult female mice were immunized with native pneumococcal PS (PPS) of serotypes 1, 6B, and 19F or PPS conjugated to tetanus protein (Pnc-TT), and PPS-specific antibodies were measured in sera of mothers and their offspring. Effective transmission of maternal antibodies was observed, as PPS-specific immunoglobulin G levels in 3-week-old offspring of immunized mothers were 37 to 322% of maternal titers, and a significant correlation between maternal and offspring antibody levels was observed. The PPS-specific antibodies persisted for several weeks but slowly decreased over time. Offspring of Pnc-TT-immunized mothers were protected against pneumococcal infections with homologous serotypes, whereas PPS immunization of mothers did not protect their offspring, in agreement with the low titer of maternal PPS specific antibodies. When adult female mice were immunized with a meningococcal serogroup C conjugate vaccine (MenC-CRM), antibody response and transmission were similar to those observed for pneumococcal antibodies. Importantly, bactericidal activity was demonstrated in offspring of MenC-CRM-immunized mothers. These results demonstrate that this murine model of pneumococcal immunization and infections is suitable to study maternal immunization strategies for protection of offspring against encapsulated bacteria.
doi:10.1128/IAI.72.1.187-195.2004
PMCID: PMC343960  PMID: 14688096
11.  Pneumococcal Serotype 19F Conjugate Vaccine Induces Cross-Protective Immunity to Serotype 19A in a Murine Pneumococcal Pneumonia Model  
Infection and Immunity  2003;71(5):2956-2959.
Immunization with a pneumococcal conjugate vaccine (PNC) containing serotype 19F induces cross-reactive antibodies to 19A in mice and human infants. Active immunization with PNC and passive immunization with serum samples from infants vaccinated with PNC containing serotype 19F, but not serotype 19A, protected against lung infection caused by both serotypes in a murine model.
doi:10.1128/IAI.71.5.2956-2959.2003
PMCID: PMC153277  PMID: 12704178
12.  Intranasal Immunization with Pneumococcal Conjugate Vaccines with LT-K63, a Nontoxic Mutant of Heat-Labile Enterotoxin, as Adjuvant Rapidly Induces Protective Immunity against Lethal Pneumococcal Infections in Neonatal Mice 
Infection and Immunity  2002;70(3):1443-1452.
Immunization with pneumococcal polysaccharides (PPS) conjugated to tetanus toxoid (TT) (Pnc-TT) elicits protective immunity in an adult murine pneumococcal infection model. To assess immunogenicity and protective immunity in early life, neonatal (1 week old) and infant (3 weeks old) mice were immunized intranasally (i.n.) or subcutaneously (s.c.) with Pnc-TT of serotype 1 (Pnc1-TT). Anti-PPS-1 and anti-TT immunoglobulin G (IgG) and IgM antibodies were measured in serum and saliva, and vaccine-induced protection was evaluated by i.n. challenge with serotype 1 pneumococci. Pnc1-TT was immunogenic in neonatal and infant mice when administered s.c. without adjuvant: a majority of the young mice were protected from bacteremia and a reduction of pneumococcal density in the lungs was observed, although antibody responses and protective efficacy remained lower than in adults. The addition of LT-K63, a nontoxic mutant of heat-labile enterotoxin, as adjuvant significantly enhanced PPS-1-specific IgG responses and protective efficacy following either s.c. or i.n. Pnc1-TT immunization. Mucosal immunization was particularly efficient in neonates, as a single i.n. dose of Pnc1-TT and LT-K63 induced significantly higher PPS-1-specific IgG responses than s.c. immunization and was sufficient to protect neonatal mice against pneumococcal infections, whereas two s.c. doses were required to induce complete protection. In addition, i.n. immunization with Pnc1-TT and LT-K63 induced a vigorous salivary IgA response. This suggests that mucosal immunization with pneumococcal conjugate vaccines and LT-K63 may be able to circumvent some of the limitations of neonatal antibody responses, which are required for protective immunity in early life.
doi:10.1128/IAI.70.3.1443-1452.2002
PMCID: PMC127807  PMID: 11854231
13.  Are the Opsonophagocytic Activities of Antibodies in Infant Sera Measured by Different Pneumococcal Phagocytosis Assays Comparable? 
Host protection against Streptococcus pneumoniae is mainly mediated by opsonin-dependent phagocytosis. Several techniques for measuring opsonophagocytic activity (OPA) of antibodies to S. pneumoniae have been standardized and used. These include the viable cell-assay, flow-cytometric assays, and an assay utilizing radiolabeled bacteria. Using these different methods, we measured the OPA of antibodies to S. pneumoniae types 6B and 19F from the sera of infants immunized with a pneumococcal conjugate vaccine, PncCRM. Generally, the results obtained by the various techniques correlated well, although serotype-specific differences were found (6B, r = 0.78 to 0.95, P < 0.001; 19F, r = 0.50 to 0.84, P < 0.001). The same serotype-specific differences were observed for the relationship between the concentrations of specific immunoglobulin G antibodies measured by enzyme immunoassay and the OPA. Since the sensitivities of the OPA assays differed, the most prominent discrepancies between the techniques were found at low antibody concentrations.
doi:10.1128/CDLI.8.2.363-369.2001
PMCID: PMC96064  PMID: 11238223
14.  An Analytical Model Applied to a Multicenter Pneumococcal Enzyme-Linked Immunosorbent Assay Study 
Journal of Clinical Microbiology  2000;38(6):2043-2050.
Pneumococcal conjugate vaccines will eventually be licensed after favorable results from phase III efficacy trials. After licensure of a conjugate vaccine for invasive pneumococcal disease in infants, new conjugate vaccines will likely be licensed primarily on the basis of immunogenicity data rather than clinical efficacy. Analytical methods must therefore be developed, evaluated, and validated to compare immunogenicity results accurately within and between laboratories for different vaccines. At present no analytical technique is uniformly accepted and used in vaccine evaluation studies to determine the acceptable level of agreement between a laboratory result and the assigned value for a given serum sample. This multicenter study describes the magnitude of agreement among 12 laboratories quantifying an identical series of 48 pneumococcal serum specimens from 24 individuals (quality-control sera) by a consensus immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) developed for this study. After provisional or trial antibody concentrations were assigned to the quality-control serum samples for this study, four methods for comparison of a series of laboratory-determined values with the assigned concentrations were evaluated. The percent error between assigned values and laboratory-determined concentrations proved to be the most informative of the four methods. We present guidelines that a laboratory may follow to analyze a series of quality-control sera to determine if it can reproduce the assigned antibody concentrations within an acceptable level of tolerance. While this study focused on a pneumococcal IgG ELISA, the methods that we describe are easily generalizable to other immunological assays.
PMCID: PMC86724  PMID: 10834951
15.  Isotypes and Opsonophagocytosis of Pneumococcus Type 6B Antibodies Elicited in Infants and Adults by an Experimental Pneumococcus Type 6B-Tetanus Toxoid Vaccine 
Infection and Immunity  1998;66(6):2866-2870.
Streptococcus pneumoniae is a major respiratory pathogen of infants, children, and the elderly. Polysaccharide vaccines have been useful in adult populations but do not elicit protective immunity in infants and young children. To enhance their immunogenicity, vaccines of pneumococcal polysaccharides conjugated to proteins are being developed. In this study antibody levels and opsonic activities were compared in sera of infants and adults injected with pneumococcal polysaccharide type 6B (Pn6B) conjugated to tetanus toxoid (TT) (Pn6B-TT). Healthy infants were injected with Pn6B-TT; group A was injected at 3, 4, and 6 months of age, and group B was injected at 7 and 9 months of age. A booster injection was given at 18 months. Adults were injected once. Antibodies were measured by enzyme-linked immunosorbent assay and radioimmunoassay, and their functional activities were measured by opsonophagocytosis of radiolabelled pneumococci. In adults, increases in immunoglobulin M (IgM), IgG, IgA, IgG1, and IgG2 to Pn6B were observed. Infants reached adult levels of IgG1 anti-Pn6B after the primary injections. After the booster injection the infant groups had total IgG- and IgM-Pn6B antibody levels similar to those of adults. After the booster injection, IgG1 was the dominant infant anti-Pn6B isotype and at a level higher than in vaccinated adults, but IgA and IgG2 antibodies remained at very low levels. Opsonic activity increased significantly after Pn6B-TT injections; the highest infant sera showed opsonic activity comparable to that of vaccinated adults. Overall, opsonic activity correlated best with total and IgG anti-Pn6B antibodies (r = 0.741, r = 0.653, respectively; n = 35) and was highest in sera with high levels of all Pn6B antibody isotypes. The results indicate the protective potential of a pneumococcal 6B polysaccharide protein conjugate vaccine for young infants.
PMCID: PMC108283  PMID: 9596761

Results 1-15 (15)