Capsular Polysaccharide Conjugate Vaccines against Contagious Bovine Pleuropneumonia: Immune Responses and Protection in Mice

2002 ◽  
Vol 126 (2-3) ◽  
pp. 171-182 ◽  
Author(s):  
E.R. Waite ◽  
J.B. March
Keyword(s):  
Immune Responses ◽  
Capsular Polysaccharide ◽  
Contagious Bovine Pleuropneumonia ◽  
Conjugate Vaccines

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 If Not Now, When? Nonserotype Pneumococcal Protein Vaccines

2021 ◽  
Vol 8 (12) ◽  
Author(s):  
Larry S McDaniel ◽  
Edwin Swiatlo
Keyword(s):  
Streptococcus Pneumoniae ◽  
Immune Responses ◽  
Capsular Polysaccharide ◽  
Recombinant Dna ◽  
Pneumococcal Vaccines ◽  
Recombinant Dna Technology ◽  
Conjugate Vaccines ◽  
Global Spread ◽  
Dna Technology ◽  
Mrna Technology

Abstract The sudden emergence and global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have greatly accelerated the adoption of novel vaccine strategies, which otherwise would have likely languished for years. In this light, vaccines for certain other pathogens could certainly benefit from reconsideration. One such pathogen is Streptococcus pneumoniae (pneumococcus), an encapsulated bacterium that can express >100 antigenically distinct serotypes. Current pneumococcal vaccines are based exclusively on capsular polysaccharide—either purified alone or conjugated to protein. Since the introduction of conjugate vaccines, the valence of pneumococcal vaccines has steadily increased, as has the associated complexity and cost of production. There are many pneumococcal proteins invariantly expressed across all serotypes, which have been shown to induce robust immune responses in animal models. These proteins could be readily produced using recombinant DNA technology or by mRNA technology currently used in SARS-CoV-2 vaccines. A door may be opening to new opportunities in affordable and broadly protective vaccines.

scholarly journals Conjugate-like immunogens produced as protein capsular matrix vaccines

2015 ◽  
Vol 112 (10) ◽  
pp. E1143-E1151 ◽  
Author(s):  
Ann Thanawastien ◽  
Robert T. Cartee ◽  
Thomas J. Griffin ◽  
Kevin P. Killeen ◽  
John J. Mekalanos
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Protective Immunity ◽  
The Elderly ◽  
Covalent Attachment ◽  
Carrier Protein ◽  
Elderly Age ◽  
Conjugate Vaccines ◽  
Age Cohorts ◽  
Polysaccharide Antigens

Capsular polysaccharides are the primary antigenic components involved in protective immunity against encapsulated bacterial pathogens. Although immunization of adolescents and adults with polysaccharide antigens has reduced pathogen disease burden, pure polysaccharide vaccines have proved ineffective at conferring protective immunity to infants and the elderly, age cohorts that are deficient in their adaptive immune responses to such antigens. However, T-cell–independent polysaccharide antigens can be converted into more potent immunogens by chemically coupling to a “carrier protein” antigen. Such “conjugate vaccines” efficiently induce antibody avidity maturation, isotype switching, and immunological memory in immunized neonates. These immune responses have been attributed to T-cell recognition of peptides derived from the coupled carrier protein. The covalent attachment of polysaccharide antigens to the carrier protein is thought to be imperative to the immunological properties of conjugate vaccines. Here we provide evidence that covalent attachment to carrier proteins is not required for conversion of T-independent antigens into T-dependent immunogens. Simple entrapment of polysaccharides or a d-amino acid polymer antigen in a cross-linked protein matrix was shown to be sufficient to produce potent immunogens that possess the key characteristics of conventional conjugate vaccines. The versatility and ease of manufacture of these antigen preparations, termed protein capsular matrix vaccines (PCMVs), will likely provide improvements in the manufacture of vaccines designed to protect against encapsulated microorganisms. This in turn could improve the availability of such vaccines to the developing world, which has shown only a limited capacity to afford the cost of conventional conjugate vaccines.

scholarly journals Immunologic Hyporesponsiveness to Serogroup C but Not Serogroup A following Repeated Meningococcal A/C Polysaccharide Vaccination in Saudi Arabia

2004 ◽  
Vol 11 (1) ◽  
pp. 83-88 ◽  
Author(s):  
Hani Jokhdar ◽  
Ray Borrow ◽  
Abdulrazaq Sultan ◽  
Mousaed Adi ◽  
Christine Riley ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Immune Responses ◽  
Geometric Mean ◽  
Outcome Study ◽  
Conjugate Vaccines ◽  
Bactericidal Antibody ◽  
Long Time ◽  
Repeated Doses ◽  
Clinical Outcome Study

ABSTRACT In Saudi Arabia, vaccination with the meningococcal A/C polysaccharide (MACP) vaccine is advised every 3 years. A clinical outcome study was performed to test the effect of repeat vaccination with the MACP vaccine on the immune responses among Saudi nationals who live in the Makkah and Jeddah areas. Subjects (n = 230) aged 10 to 29 years were selected: 113 subjects with two or more prior vaccinations with the MACP vaccine, 79 subjects with one prior vaccination with the MACP vaccine, and 38 subjects naïve to vaccination with the MACP vaccine. All subjects received the MACP vaccine in 2002, and serum bactericidal antibody (SBA) titers were measured before and 1 month after vaccination with the MACP vaccine. For serogroup C, geometric mean SBA titers 1 month following vaccination with the MACP vaccine were 708.6 (95% confidence interval [CI], 217.5 to 2,308.9) for those naïve to prior vaccination with the MACP vaccine, and they were significantly higher (P < 0.0001) than 25.0 (95% CI, 12.4 to 50.2) for those who had received one prior vaccination with the MACP vaccine and 32.4 (95% CI, 18.7 to 56.4) for those who had received two or more doses of the MACP vaccine. For serogroup A, the geometric mean SBA titer 1 month after receipt of the MACP vaccine was 1,649.3 (95% CI, 835.2 to 3,256.9) for those naïve to prior vaccination, and the titers were lower (P = 0.67) than 2,185.7 (95% CI, 1,489.4 to 3,207.7) for those who had received one prior dose of the MACP vaccine and significantly lower (P = 0.042) than 3,540.8 (95% CI, 2,705.2 to 4,634.5) for those who had received two or more doses of the MACP vaccine. For serogroup C, the proportions of nonresponders (SBA titers, <8) were 19% for the naïve cohort, 52% for the cohort with one prior vaccination, and 49% for the cohort with two or more prior vaccinations. Following repeated doses of the MACP vaccine, hyporesponsiveness to serogroup C is evident, with high percentages of MACP vaccinees having SBA titers below the putative protective SBA titer. Serogroup A responses following vaccination with the MACP vaccine were boosted. Introduction of the serogroup C conjugate vaccine would provide long-term protection against serogroup C disease; however, quadrivalent conjugate vaccines are required to provide long-time protection against disease caused by serogroups A, W135, and Y.

scholarly journals Establishment of a New Human Pneumococcal Standard Reference Serum, 007sp

2011 ◽  
Vol 18 (10) ◽  
pp. 1728-1736 ◽  
Author(s):  
D. Goldblatt ◽  
B. D. Plikaytis ◽  
M. Akkoyunlu ◽  
J. Antonello ◽  
L. Ashton ◽  
...  
Keyword(s):  
Immune Responses ◽  
Polysaccharide Vaccine ◽  
Reference Standard ◽  
Pneumococcal Serotypes ◽  
Conjugate Vaccines ◽  
Serum Pool ◽  
B Virus ◽  
Reference Preparation ◽  
Reference Serum ◽  
Standard Serum

ABSTRACTLot 89SF has been the reference standard serum pool used in pneumococcal enzyme-linked immunosorbent assays (ELISAs) since 1990. In 2005, it was estimated that there remained between 2 and 5 years' supply of lot 89SF. Since lot 89SF was the reference standard used in the evaluation of the seven-valent pneumococcal conjugate vaccine Prevnar (PCV7), the link to clinical efficacy would be severed if stocks became completely depleted. Furthermore, demonstration of immune responses comparable to those elicited by PCV7 is a licensure approach used for new pneumococcal conjugate vaccines, so a replacement reference standard was required. A total of 278 volunteers were immunized with the 23-valent unconjugated polysaccharide vaccine Pneumovax II, and a unit of blood was obtained twice within 120 days following immunization. Plasma was prepared, pooled, and confirmed to be free from hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV. The pooled serum was poured at 6 ml per vial into 15,333 vials and lyophilized. Immunological bridging of 007sp to 89SF was used to establish equivalent reference values for 13 pneumococcal capsular serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) by five independent laboratories. Antibody concentrations in 007sp were established relative to the lot 89SF reference preparation using the WHO reference ELISA. Subsequently, 12 existing WHO calibration sera had concentrations reassigned for 13 pneumococcal serotypes using new serum 007sp as the reference, and these were compared to concentrations relative to the original reference serum. Agreement was excellent for the 12 WHO calibration sera. The 007sp preparation has replaced 89SF as the pneumococcal reference standard. Sufficient quantity of this new preparation is available such that, with judicious use, it should be available for at least 25 years.

scholarly journals Immunogenicity of a Heptavalent Conjugate Pneumococcal Vaccine Administered Concurrently with a Combination Diphtheria, Tetanus, Five-Component Acellular Pertussis, Inactivated Polio, and Haemophilus influenzae Type b Vaccine and a Meningococcal Group C Conjugate Vaccine at 2, 3, and 4 Months of Age

2009 ◽  
Vol 17 (3) ◽  
pp. 311-316 ◽  
Author(s):  
S. J. Moss ◽  
A. C. Fenton ◽  
J. Toomey ◽  
A. Grainger ◽  
R. Borrow ◽  
...  
Keyword(s):  
Immune Responses ◽  
Haemophilus Influenzae ◽  
Conjugate Vaccine ◽  
Capsular Polysaccharide ◽  
Geometric Mean ◽  
Haemophilus Influenzae Type ◽  
Type B ◽  
Term Infants ◽  
Meningococcal Group ◽  
Pneumococcal Serotype

ABSTRACT The immunogenicities of conjugate pneumococcal vaccines have been demonstrated when they are administered at 2, 3, and 4 months of age. There is a paucity of data on the immunogenicity of this vaccine when it is administered concurrently with other vaccines in the primary immunization schedule of the United Kingdom. We immunized 55 term infants at 2, 3, and 4 months of age with the seven-valent pneumococcal conjugate vaccine (PCV7), the meningococcal group C conjugate (MCC) vaccine, and the diphtheria, tetanus, five-component acellular pertussis, inactivated polio, and Haemophilus influenzae type b (DTaP5/IPV/Hib-TT) vaccine. The immune responses to the H. influenzae type b (Hib), MCC, and tetanus vaccines were measured at 2, 5, and 12 months of age; and the immune responses to PCV7 were measured at 2 and 5 months and then either at 12 months or following a 4th dose of PCV7. There were increases in the geometric mean concentrations (GMCs) of all antigens postimmunization. Greater than or equal to 90% of the infants achieved putatively protective levels postimmunization for all vaccine antigens except pneumococcal serotype 6B and Hib. The GMCs of the PCV7 serotypes increased following a 4th dose, although one infant had not reached putative levels of protection against serotype 6B. In conclusion, when infants were vaccinated according to the schedule described above, they had lower postprimary immunization responses to Hib, meningococcus group C capsular polysaccharide, and pneumococcal serotype 6B than the responses demonstrated by use of the other schedules. Despite this finding, there was a good response following a 4th dose of PCV7.

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