scholarly journals The Pneumococcal Polysaccharide-Tetanus Toxin Native C-Fragment Conjugate Vaccine: The Carrier Effect and Immunogenicity

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Rui Yu ◽  
Junjie Xu ◽  
Tao Hu ◽  
Wei Chen
Keyword(s):  
Tetanus Toxin ◽  
Capsular Polysaccharide ◽  
Low Cost ◽  
Culture Conditions ◽  
Carrier Protein ◽  
Pneumococcal Infections ◽  
Conjugate Vaccines ◽  
Carrier Effect ◽  
Encapsulated Bacteria ◽  
Antibody Levels

The encapsulated bacteria, as Streptococcus pneumonia, Haemophilus influenzae type b, and Neisseria meningitidis, cause serious morbidity and mortality worldwide. The capsular polysaccharide (PS), which could elicit a weak T cell-independent immune response, is a vital virulence determinant. One of the strategies to improve the PS-specific immunogenicity is to conjugate PS with a nontoxic carrier protein. Tetanus toxoid (TT) and CRM197 are the typical carrier proteins for the PS conjugate vaccines. TT is the inactivated tetanus toxin manipulated with formaldehyde, which suffers from the pollution from residual formaldehyde and the incomplete detoxification. CRM197 has the disadvantage of low-yield purification with the requirement of sophisticated culture conditions. Thus, a novel carrier protein without these disadvantages is highly required. The tetanus toxin native C-fragment (Hc) is safe, low-cost, and highly immunogenic with easy purification, which can act as a promising carrier protein. Pneumococcal serogroups 14 and 23F were major epidemic causes of pneumococcal infections. In the present study, the capsular PSs (PS14 and PS23F) were conjugated with Hc, TT, and CRM197, respectively. TT- and CRM197-based conjugates acted as controls for Hc-based conjugates (PS14-Hc and PS23F-Hc). The structural properties of Hc were not fundamentally changed after conjugated with PS. PS14-Hc and PS23F-Hc could potentiate sound PS-specific antibody levels comparable to the controls. Thus, Hc exhibited a practical carrier effect to help the pneumococcal conjugate vaccines perform good immunogenicities.

scholarly journals Safety and Immunogenicity of Vi Conjugate Vaccines for Typhoid Fever in Adults, Teenagers, and 2- to 4-Year-Old Children in Vietnam

1999 ◽  
Vol 67 (11) ◽  
pp. 5806-5810 ◽  
Author(s):  
Zuzana Kossaczka ◽  
Feng-Ying C. Lin ◽  
Vô Anh Ho ◽  
Nguyen Thi Thanh Thuy ◽  
Phan Van Bay ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Typhoid Fever ◽  
Capsular Polysaccharide ◽  
Geometric Mean ◽  
Salmonella Typhi ◽  
Enzyme Linked Immunosorbent Assay ◽  
Conjugate Vaccines ◽  
Local Reactions ◽  
Antibody Levels ◽  
Igg Level

ABSTRACT The capsular polysaccharide of Salmonella typhi, Vi, is an essential virulence factor and a protective vaccine for people older than 5 years. The safety and immunogenicity of two investigational Vi conjugate vaccines were evaluated in adults, 5- to 14-year-old children, and 2- to 4-year-old children in Vietnam. The conjugates were prepared with Pseudomonas aeruginosa recombinant exoprotein A (rEPA) as the carrier, using eitherN-succinimidyl-3-(2-pyridyldithio)-propionate (SPDP; Vi-rEPA1) or adipic acid dihydrazide (ADH; Vi-rEPA2) as linkers. None of the recipients experienced a temperature of >38.5°C or significant local reactions. One injection of Vi-rEPA2 into adults elicited a geometric mean (GM) increase in anti-Vi immunoglobulin G (IgG) from 9.62 enzyme-linked immunosorbent assay units/ml (EU) to 465 EU at 6 weeks; this level fell to 119 EU after 26 weeks. In the 5- to 14-year-old children, anti-Vi IgG levels at 6 weeks elicited by Vi-rEPA2, Vi-rEPA1, and Vi were 169, 22.8, and 18.9 EU, respectively (P = 0.0001 for Vi-rEPA1 and Vi with respect to Vi-rEPA2). At 26 weeks, the anti-Vi IgG levels for recipients of Vi-rEPA2, Vi-rEPA1, and Vi were 30.0, 10.8, and 13.4 EU, respectively (P < 0.001 for Vi-rEPA1 and Vi with respect to Vi-rEPA2); all were higher than the preinjection levels (P = 0.0001). Vi-rEPA2 also elicited the highest anti-Vi IgM and IgA levels of the three vaccines. In the 2- to 4-year-old children at 6 weeks following the first injection, Vi-rEPA2 elicited an anti-Vi IgG level of 69.9 EU compared to 28.9 EU for Vi-rEPA1(P = 0.0001). Reinjection increased Vi antibody levels from 69.9 to 95.4 EU for Vi-rEPA2 and from 28.9 to 83.0 EU for Vi-rEPA1. At 26 weeks, anti-Vi IgG levels remained higher than those at preinjection (30.6 versus 0.18 for Vi-rEPA2 and 12.8 versus 0.33 for Vi-rEPA1; P = 0.0001 for both). Vi vaccine is recommended for individuals of 5 years of age or older. In the present study, the GM level of anti-Vi IgG elicited by two injections of Vi-rEPA2 in the 2- to 4-year-old children was higher than that elicited by Vi in the 5- to 14-year-old children (30.6 versus 13.4; P = 0.0001). The safety and immunogenicity of the Vi-rEPA2conjugate warrant further investigation.

scholarly journals Pneumococcal Capsular Polysaccharide Immunity in the Elderly

2017 ◽  
Vol 24 (6) ◽  
Author(s):  
Hugh Adler ◽  
Daniela M. Ferreira ◽  
Stephen B. Gordon ◽  
Jamie Rylance
Keyword(s):  
Older People ◽  
Pneumococcal Disease ◽  
Capsular Polysaccharide ◽  
The Elderly ◽  
Pneumococcal Infections ◽  
Opsonic Activity ◽  
Serotype Replacement ◽  
Colonization Dynamics ◽  
And Function ◽  
Antibody Levels

ABSTRACT Immunity to pneumococcal infections is impaired in older people, and current vaccines are poorly protective against pneumococcal disease in this population. Naturally acquired immunity to pneumococcal capsular polysaccharides develops during childhood and is robust in young adults but deteriorates with advanced age. In particular, antibody levels and function are reduced in older people. Pneumococcal vaccines are recommended for people >65 years old. However, the benefits of polysaccharide and protein-conjugated vaccines in this population are small, because of both serotype replacement and incomplete protection against vaccine serotype pneumococcal disease. In this review, we overview the immune mechanisms by which naturally acquired and vaccine-induced pneumococcal capsular polysaccharide immunity declines with age, including altered colonization dynamics, reduced opsonic activity of antibodies (particularly IgM), and impaired mucosal immunity.

scholarly journals Intranasal Immunization with Pneumococcal Polysaccharide Conjugate Vaccines with Nontoxic Mutants of Escherichia coliHeat-Labile Enterotoxins as Adjuvants Protects Mice against Invasive Pneumococcal Infections

1999 ◽  
Vol 67 (11) ◽  
pp. 5892-5897 ◽  
Author(s):  
Håvard Jakobsen ◽  
Dominique Schulz ◽  
Mariagrazia Pizza ◽  
Rino Rappuoli ◽  
Ingileif Jónsdóttir
Keyword(s):  
Immune Responses ◽  
Protein Antigens ◽  
Pneumococcal Infections ◽  
Igg Antibody ◽  
Adjuvant Activity ◽  
Conjugate Vaccines ◽  
Mucosal Vaccination ◽  
Serum Igg ◽  
Mucosal Immune Responses ◽  
Antibody Levels

ABSTRACT Host defenses against Streptococcus pneumoniae depend largely on phagocytosis following opsonization by polysaccharide-specific immunoglobulin G (IgG) antibodies and complement. Since colonization of the respiratory mucosa is the first step in pneumococcal pathogenesis, mucosal immune responses may play a significant role. In addition to inducing systemic immune responses, mucosal vaccination with an effective adjuvant has the advantage of inducing mucosal IgA antibodies. The heat-labile enterotoxin (LT) ofEscherichia coli is a well-studied mucosal adjuvant, and adjuvant activity of nontoxic LT mutants has been demonstrated for several protein antigens. We investigated the immunogenicity of pneumococcal polysaccharide conjugate vaccines (PNC) of serotypes 1 and 3 in mice after intranasal (i.n.) immunization by using as an adjuvant the nontoxic LT mutant LT-K63 or LT-R72, which has minimal residual toxicity. Pneumococcal serotype-specific antibodies were measured in serum (IgM, IgG, and IgA) and saliva (IgA), and vaccine-induced protection was evaluated by i.n. challenge with virulent pneumococci of the homologous serotype. When administered with LT mutants, i.n. immunization with both conjugates induced systemic and mucosal immune responses, and serum IgG antibody levels were significantly higher than after subcutaneous immunization. All mice immunized i.n. with PNC-1 and LT mutants were protected against bacteremia and cleared the pneumococci from the lung 24 h after i.n. challenge; pneumococcal density correlated significantly with serum IgG antibody levels. Similarly, the survival of mice immunized i.n. with PNC-3 and LT mutants was significantly prolonged. These results demonstrate that i.n. vaccination with PNC and potent adjuvants can protect mice against invasive and lethal pneumococcal infections, indicating that mucosal vaccination with PNC may be an alternative vaccination strategy for humans.

scholarly journals N19 Polyepitope as a Carrier for Enhanced Immunogenicity and Protective Efficacy of Meningococcal Conjugate Vaccines

2004 ◽  
Vol 72 (8) ◽  
pp. 4884-4887 ◽  
Author(s):  
Karin Baraldo ◽  
Elena Mori ◽  
Antonella Bartoloni ◽  
Roberto Petracca ◽  
Aldo Giannozzi ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Capsular Polysaccharide ◽  
Protective Efficacy ◽  
Cd4 T Cell ◽  
T Cell Epitopes ◽  
Conjugate Vaccines ◽  
Carrier Effect ◽  
Bactericidal Antibody ◽  
Antibody Titers

ABSTRACT N19, a string of human universal CD4 T-cell epitopes from various pathogen-derived antigens, was shown to exert a stronger carrier effect than CRM197 for the induction of anti-group C Neisseria meningitidis capsular polysaccharide (MenC), after immunization of mice with various dosages of N19-MenC or CRM-MenC conjugate vaccines. After two immunizations, the N19-based construct induced anti-MenC antibody and protective bactericidal antibody titers higher than those induced by three doses of the CRM-MenC conjugate and required lower amounts of conjugate. N19-based conjugates are superior to CRM-based conjugates to induce protective immune responses to MenC conjugates.

scholarly journals Immunization of Female Mice with Glycoconjugates Protects Their Offspring against Encapsulated Bacteria

2004 ◽  
Vol 72 (1) ◽  
pp. 187-195 ◽  
Author(s):  
Margret Y. Richter ◽  
Håvard Jakobsen ◽  
Alda Birgisdottir ◽  
Jean-François Haeuw ◽  
Ultan F. Power ◽  
...  
Keyword(s):  
Adult Female ◽  
Murine Model ◽  
Pneumococcal Infections ◽  
Specific Antibodies ◽  
Female Mice ◽  
Immunization Strategies ◽  
Pneumococcal Bacteremia ◽  
Encapsulated Bacteria ◽  
Antibody Levels ◽  
Effective Transmission

ABSTRACT 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.

scholarly journals INVESTIGATION OF IMMUNOGENICITY AND SAFETY OF 23-VALENT POLYSACCHARIDE PNEUMOCOCCAL VACCINE IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

2018 ◽  
Vol 56 (4) ◽  
pp. 433-438 ◽  
Author(s):  
G. M. Tarasova ◽  
B. S. Belov ◽  
D. V. Bukhanova ◽  
M. V. Cherkasova ◽  
S. K. Solovyev ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Pneumococcal Vaccine ◽  
Capsular Polysaccharide ◽  
Vaccine Response ◽  
Systemic Lupus ◽  
Good Tolerability ◽  
Antibody Levels ◽  
Polysaccharide Pneumococcal Vaccine

Objective: to investigate the safety and immunogenicity of 23-valent polysaccharide pneumococcal vaccine (PPV-23) in patients with systemic lupus erythematosus (SLE). Subjects and methods. The investigation enrolled 30 patients with a reliable diagnosis of SLE; of them there were 27 women and 3 men at the age of 19 to 62 years. The disease duration ranged from 9 months to 20 years. At the time of inclusion in the investigation, the disease activity was high in 2 patients, moderate in 3, and low in 20; five patients were in remission. During a year before vaccination, pneumonia was detected in 5 (16.7%) of the 30 patients; there were a total of 18 episodes of various respiratory and ENT infections. The patients were examined at baseline and at 1, 3 and 12 months after vaccination. Standard clinical and laboratory studies and a detailed blood immunological analysis were carried out at visits. The levels of IgG antibodies to capsular polysaccharide pneumococcus were determined during each visit. Twenty-nine patients received glucocorticoids (GCs) at a dose of 5–30 mg/day; 24 – hydroxychloroquine; 14 – cytostatics (CS); 10 – biological agents (BAs) (5 – rituximab, 5 – belimumab). A single dose of 0.5 ml of PPV-23 (Pneumo 23, Aventis) was subcutaneously injected into the upper outer arm. Vaccination was done during the ongoing therapy with GC/CS and belimumab, as well as at least 1 month before the first (next) administration and/or 4.5–5 months after the last rituximab infusion. Results and discussion. 60% of patients were observed to have mild and moderate standard local vaccine reactions; 1 (3.3%) patient had a local hyperergic reaction eliminated within 7 days of the local application of antihistamines and GCs. During the follow-up, there was no SLE exacerbation significantly associated with the vaccination performed. No new autoimmune phenomena were found in any of the cases. A year after vaccination, a significant (2-fold or more) increase in anti-pneumococcal antibody levels remained in 19 (63.3%) patients (respondents); 36.7% of patients were nonrespondents. Among the patients who received a BA, the non-responders were significantly more than among those who did not take the drug (7 (70%) and 4 (20%), respectively) (p = 0.01). When treated with rituximab and belimumab, the number of non-respondents was comparable (4 and 3, respectively). The immunogenicity of PPV-23 was independent of the degree of SLE activity: the vaccine response was absent in 1 out of the 5 patients with high (n = 2) and medium (n = 3) SLE activities, as well as in 10 out of the 25 patients with low disease activity and remission. There was no development of considerable adverse reactions after vaccination in patients with high and medium SLE activity. The overall clinical efficiency of vaccination was 93.3%. Conclusion. Thus, PPV-23 shows a good tolerability and a sufficient immunogenicity in patients with SLE. There is a need for further investigations conducted in large samples of patients during long-term follow-ups in order to more fully evaluate the clinical efficacy, tolerability, and immunogenicity of PPV-23.

scholarly journals SEROTYPING OF STREPTOCOCCUS PNEUMONIAE STRAINS, ISOLATED FROM CHILDREN IN URAL REGION WITH THE USE OF MULTIPLEX PCR

2012 ◽  
Vol 17 (5) ◽  
pp. 26-30
Author(s):  
E. V. Samatova ◽  
A. E. Druy ◽  
G. A. Tsaur ◽  
L. G. Boronina
Keyword(s):  
Streptococcus Pneumoniae ◽  
Multiplex Pcr ◽  
Inflammatory Diseases ◽  
Ural Region ◽  
Coincidence Rate ◽  
Pneumococcal Infections ◽  
Conjugate Vaccines

This article presents results of the multiplex PCR investigation of the serotypes distribution of S. pneumoniae strains circulating in Ekaterinburg and the Sverdlovsk region. This study was performed in children with invasive, noninvasive pneumococcal infections and carriers. 118 strains of pneumococci typed out of 129 ones (91.5%) referred to the 15 serotypes: 6A, 6B (20,8%); 23F (13,9%); 19F (11,5%); 8, 9V, 9A, 11F, 11A, 11B, 11C, 11D, 12F, 15A, 33F (11,5%); 3 (10%) 2, 15F, 17F, 22F, 23B (3,9%); 18B, 18C (3.9%), 19A (3,2%); 7F, 19B, 19C, 23A (3,2%); 5,10A (1.6%), 20 (1.6%), 14 (1, 6%); 9L, 9N, 15B, 15C (1,6%); 18F (1,6%); 18A (1.6%). Coincidence rate of serotypes S. pneumoniae, isolated from children with chronic infectious and inflammatory diseases of the lung with serotypes included into the content of the conjugate vaccines is: 7-valent - 69.3%, 10-valent - 98.2%, 11 - and 13-valent - 100%.

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