scholarly journals Age-Specific Immunoglobulin G (IgG) and IgA to Pneumococcal Protein Antigens in a Population in Coastal Kenya

2004 ◽  
Vol 72 (6) ◽  
pp. 3331-3335 ◽  
Author(s):  
Catherine Laine ◽  
Tabitha Mwangi ◽  
Claudette M. Thompson ◽  
Jacktone Obiero ◽  
Marc Lipsitch ◽  
...  
Keyword(s):  
Immunoglobulin G ◽  
Protein A ◽  
Age Groups ◽  
Surface Protein ◽  
The Elderly ◽  
Antibody Responses ◽  
Sub Saharan Africa ◽  
Protein Antigens ◽  
Coastal Kenya ◽  
Iga Antibody

ABSTRACT Streptococcus pneumoniae is the primary etiological agent of community-acquired pneumonia and a major cause of meningitis and bacteremia. Three conserved pneumococcal proteins—pneumolysin, pneumococcal surface adhesin A (PsaA), and pneumococcal surface protein A (PspA)—are currently being investigated as vaccine candidates. Such protein-based vaccines, if proven effective, could provide a cheaper alternative to conjugate vaccine formulae. Few data from sub-Saharan Africa exist concerning the development of natural antibody to these antigens, however. To investigate the age-specific development of antiprotein immunoglobulin G (IgG) and IgA antibody responses, the sera of 220 persons 2 weeks to 84 years of age from coastal Kenya were assayed using enzyme-linked immunosorbent assays. IgG and IgA antibody responses to each antigen were observed in all age groups. Serum concentrations of IgG and IgA antibody responses to PspA and PdB (a recombinant toxoid derivative of pneumolysin), but not to PsaA, increased significantly with age (P < 0.001). No decline was observed in the sera of the elderly. Anti-protein IgG concentrations were only weakly correlated (0.30 < r < 0.56; P < 0.0001), as were IgA concentrations (0.24 < r < 0.54; P < 0.0001).

scholarly journals A Novel, Multiple-Antigen Pneumococcal Vaccine Protects against LethalStreptococcus pneumoniaeChallenge

2018 ◽  
Vol 87 (3) ◽  
Author(s):  
Win-Yan Chan ◽  
Claire Entwisle ◽  
Giuseppe Ercoli ◽  
Elise Ramos-Sevillano ◽  
Ann McIlgorm ◽  
...  
Keyword(s):  
Heat Shock ◽  
Protein A ◽  
Surface Protein ◽  
Surface Proteins ◽  
Rabbit Serum ◽  
Protein Antigens ◽  
Content Type ◽  
Multiple Antigen ◽  
Bacterial Lysates ◽  
Chromatography Step

ABSTRACTCurrent vaccination againstStreptococcus pneumoniaeuses vaccines based on capsular polysaccharides from selected serotypes and has led to nonvaccine serotype replacement disease. We have investigated an alternative serotype-independent approach, using multiple-antigen vaccines (MAV) prepared fromS. pneumoniaeTIGR4 lysates enriched for surface proteins by a chromatography step after culture under conditions that induce expression of heat shock proteins (Hsp; thought to be immune adjuvants). Proteomics and immunoblot analyses demonstrated that, compared to standard bacterial lysates, MAV was enriched with Hsps and contained several recognized protective protein antigens, including pneumococcal surface protein A (PspA) and pneumolysin (Ply). Vaccination of rodents with MAV induced robust antibody responses to multiple serotypes, including nonpneumococcal conjugate vaccine serotypes. Homologous and heterologous strains ofS. pneumoniaewere opsonized after incubation in sera from vaccinated rodents. In mouse models, active vaccination with MAV significantly protected against pneumonia, while passive transfer of rabbit serum from MAV-vaccinated rabbits significantly protected against sepsis caused by both homologous and heterologousS. pneumoniaestrains. Direct comparison of MAV preparations made with or without the heat shock step showed no clear differences in protein antigen content and antigenicity, suggesting that the chromatography step rather than Hsp induction improved MAV antigenicity. Overall, these data suggest that the MAV approach may provide serotype-independent protection againstS. pneumoniae.

scholarly journals Heterogeneous Antibody Responses in Tuberculosis

1998 ◽  
Vol 66 (8) ◽  
pp. 3936-3940 ◽  
Author(s):  
Konstantin Lyashchenko ◽  
Roberto Colangeli ◽  
Michel Houde ◽  
Hamdan Al Jahdali ◽  
Dick Menzies ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Antibody Response ◽  
Immunosorbent Assay ◽  
Immunoglobulin G ◽  
Antigen Recognition ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protein Antigens ◽  
Tuberculosis Patients ◽  
Specific Antibodies

ABSTRACT Antibody responses during tuberculosis were analyzed by an enzyme-linked immunosorbent assay with a panel of 10 protein antigens of Mycobacterium tuberculosis. It was shown that serum immunoglobulin G antibodies were produced against a variety of M. tuberculosis antigens and that the vast majority of sera from tuberculosis patients contained antibodies against one or more M. tuberculosis antigens. The number and the species of serologically reactive antigens varied greatly from individual to individual. In a given serum, the level of specific antibodies also varied with the antigen irrespective of the total number of antigens recognized by that particular serum. These findings indicate that person-to-person heterogeneity of antigen recognition, rather than recognition of particular antigens, is a key attribute of the antibody response in tuberculosis.

scholarly journals PspA Family Distribution, unlike Capsular Serotype, Remains Unaltered following Introduction of the Heptavalent Pneumococcal Conjugate Vaccine

2012 ◽  
Vol 19 (6) ◽  
pp. 891-896 ◽  
Author(s):  
Christina M. Croney ◽  
Mamie T. Coats ◽  
Moon H. Nahm ◽  
David E. Briles ◽  
Marilyn J. Crain
Keyword(s):  
Pneumococcal Disease ◽  
Protein A ◽  
Surface Protein ◽  
The United States ◽  
Pediatric Hospital ◽  
Protein Antigens ◽  
Conjugate Vaccines ◽  
Reactive Protein ◽  
Serotype Replacement ◽  
Heptavalent Pneumococcal Conjugate Vaccine

ABSTRACTPneumococcal conjugate vaccines (PCVs) are recommended for the prevention of invasive pneumococcal disease (IPD) in young children. Since the introduction of the heptavalent pneumococcal vaccine (PCV7) in 2000, IPD caused by serotypes in the vaccine has almost been eliminated, and previously uncommon capsular serotypes now cause most cases of pediatric IPD in the United States. One way to protect against these strains would be to add cross-reactive protein antigens to new vaccines. One such protein is pneumococcal surface protein A (PspA). Prior to 2000, PspA families 1 and 2 were expressed by 94% of isolates. Because PCV7 vaccine pressure has resulted in IPD caused by capsular serotypes that were previously uncommon and unstudied for PspA expression, it was possible that many of the new strains expressed different PspA antigens or even lacked PspA. Of 157 pediatric invasive pneumococcal isolates collected at a large pediatric hospital in Alabama between 2002 and 2010, only 60.5% had capsular serotypes included in PCV13, which came into general use in Alabama after our strains were collected. These isolates included 17 serotypes that were not covered by PCV13. Nonetheless, pneumococcal capsular serotype replacement was not associated with changes in PspA expression; 96% of strains in this collection expressed PspA family 1 or 2. Continued surveillance will be critical to vaccine strategies to further reduce IPD.

scholarly journals Growth‐Inhibiting Antibody Responses of Humans Vaccinated with Recombinant Outer Surface Protein A or Infected withBorrelia burgdorferior Both

2000 ◽  
Vol 181 (3) ◽  
pp. 1062-1068 ◽  
Author(s):  
Catherine J. Luke ◽  
Margaret A. Marshall ◽  
John M. Zahradnik ◽  
Michael Bybel ◽  
Barry E. Menefee ◽  
...  
Keyword(s):  
Outer Surface ◽  
Protein A ◽  
Surface Protein ◽  
Antibody Responses ◽  
Outer Surface Protein A ◽  
Outer Surface Protein ◽  
Growth Inhibiting

scholarly journals Host-Adapted Borrelia burgdorferi in Mice Expresses OspA during Inflammation

2003 ◽  
Vol 71 (7) ◽  
pp. 4003-4010 ◽  
Author(s):  
Helena Crowley ◽  
Brigitte T. Huber
Keyword(s):  
Borrelia Burgdorferi ◽  
Protein A ◽  
Surface Protein ◽  
Conclusive Evidence ◽  
Antibody Responses ◽  
In Vivo Model ◽  
Mammalian Host ◽  
Outer Surface Protein A ◽  
Reverse Transcription Pcr

ABSTRACT Antibody responses to outer surface protein A (OspA) of Borrelia burgdorferi may occur during periods of arthritis late in the clinical course of untreated Lyme disease. These antibody responses are paradoxical, given the conclusive evidence demonstrating that B. burgdorferi transmitted to the mammalian host expresses little or no OspA. The parallel occurrence of OspA antibodies and arthritic episodes suggests that OspA expression is upregulated during infection with B. burgdorferi. We hypothesized that this was due to the inflammatory environment caused by the immune response to the spirochete. To test our hypothesis, we adapted an in vivo model that mimics the host-pathogen interaction. Dialysis chambers containing B. burgdorferi were implanted into the peritoneal cavities of mice in the presence or absence of zymosan, a yeast cell wall extract that induces inflammation. Spirochetes were harvested 2 days later, and OspA expression was assessed at the protein and transcription level by Western blotting and real-time reverse transcription-PCR, respectively. Flow cytometry was also utilized to evaluate OspA protein expression on individual spirochetes. B. burgdorferi maintained in an inflammatory in vivo environment show an increased OspA expression relative to B. burgdorferi kept under normal in vivo conditions. Furthermore, host-adapted B. burgdorferi with a low OspA phenotype upregulates OspA expression when transferred to an inflammatory in vivo environment. The results obtained by these techniques uniformly identify inflammation as a mediator of in vivo OspA expression in host-adapted B. burgdorferi, providing insights into the behavior of live spirochetes in the mammalian host.

scholarly journals Protective immunity elicited by recombinant bacille Calmette-Guerin (BCG) expressing outer surface protein A (OspA) lipoprotein: a candidate Lyme disease vaccine.

1993 ◽  
Vol 178 (1) ◽  
pp. 197-209 ◽  
Author(s):  
C K Stover ◽  
G P Bansal ◽  
M S Hanson ◽  
J E Burlein ◽  
S R Palaszynski ◽  
...  
Keyword(s):  
Outer Surface ◽  
Protein A ◽  
Surface Protein ◽  
Antibody Responses ◽  
Target Antigen ◽  
Bacille Calmette Guerin ◽  
Protective Antibody ◽  
Outer Surface Protein A ◽  
Outer Surface Protein ◽  
Recombinant Bcg

The current vaccine against tuberculosis, Mycobacterium bovis strain bacille Calmette-Guerin (BCG), offers potential advantages as a live, innately immunogenic vaccine vehicle for the expression and delivery of protective recombinant antigens (Stover, C.K., V.F. de la Cruz, T.R. Fuerst, J.E. Burlein, L.A. Benson, L.T. Bennett, G.P. Bansal, J.F. Young, M.H. Lee, G.F. Hatfull et al. 1991. Nature [Lond]. 351:456; Jacobs, W.R., Jr., S.B. Snapper, L. Lugosi and B.R. Bloom. 1990. Curr. Top. Microbiol. Immunol. 155:153; Jacobs, W.R., M. Tuckman, and B.R. Bloom. 1987. Nature [Lond.]. 327:532); but as an attenuated intracellular bacterium residing in macrophages, BCG would seem to be best suited for eliciting cellular responses and not humoral responses. Since bacterial lipoproteins are often among the most immunogenic of bacterial antigens, we tested whether BCG expression of a target antigen as a membrane-associated lipoprotein could enhance the potential for a recombinant BCG vaccine to elicit high-titered protective antibody responses to target antigens. Immunization of mice with recombinant BCG vaccines expressing the outer surface protein A (OspA) antigen of Borrelia burgdorferi as a membrane-associated lipoprotein resulted in protective antibody responses that were 100-1,000-fold higher than responses elicited by immunization with recombinant BCG expressing OspA cytoplasmically or as a secreted fusion protein. Furthermore, these improved antibody responses were observed in heterogeneous mouse strains that vary in their immune responsiveness to OspA and sensitivity to BCG growth. Thus, expression of protective antigens as chimeric membrane-associated lipoproteins on recombinant BCG may result in the generation of new candidate vaccines against Lyme borreliosis and other human or veterinary diseases where humoral immunity is the protective response.

scholarly journals Impaired Immunogenicity of Meningococcal Neisserial Surface Protein A in Human Complement Factor H Transgenic Mice

2015 ◽  
Vol 84 (2) ◽  
pp. 452-458 ◽  
Author(s):  
Eduardo Lujan ◽  
Rolando Pajon ◽  
Dan M. Granoff
Keyword(s):  
Transgenic Mice ◽  
Outer Membrane ◽  
Protein A ◽  
Surface Protein ◽  
Factor H ◽  
Antibody Responses ◽  
Complement Factor ◽  
Wild Type ◽  
Protective Antibody ◽  
Bactericidal Antibody

Neisserial surface protein A (NspA) is a highly conserved outer membrane protein previously investigated as a meningococcal vaccine candidate. Despite eliciting serum bactericidal activity in mice, a recombinant NspA vaccine failed to elicit serum bactericidal antibodies in a phase 1 clinical trial in humans. The discordant results may be explained by the recent discovery that NspA is a human-specific ligand of the complement inhibitor factor H (FH). Therefore, in humans but not mice, NspA would be expected to form a complex with FH, which could impair human anti-NspA protective antibody responses. To investigate this question, we immunized human FH transgenic BALB/c mice with three doses of recombinant NspA expressed inEscherichia colimicrovesicles, with each dose being separated by 3 weeks. Three of 12 (25%) transgenic mice and 13 of 14 wild-type mice responded with bactericidal titers of ≥1:10 in postimmunization sera (P= 0.0008, Fisher's exact test). In contrast, human FH transgenic and wild-type mice immunized with a control meningococcal native outer membrane vesicle vaccine had similar serum bactericidal antibody responses directed at PorA, which is not known to bind human FH, and a mutant factor H binding protein (FHbp) antigen with a >50-fold lower level of FH binding than wild-type FHbp antigen binding.Thus, human FH can impair anti-NspA serum bactericidal antibody responses, which may explain the poor immunogenicity of the NspA vaccine previously tested in humans. A mutant NspA vaccine engineered to have decreased binding to human FH may increase protective antibody responses in humans.

scholarly journals Immune Responses to Specific Antigens of Streptococcus pneumoniae and Moraxella catarrhalis in the Respiratory Tract

2000 ◽  
Vol 68 (3) ◽  
pp. 1569-1573 ◽  
Author(s):  
Takao Samukawa ◽  
Noboru Yamanaka ◽  
Susan Hollingshead ◽  
Karin Klingman ◽  
Howard Faden
Keyword(s):  
Streptococcus Pneumoniae ◽  
Immune Responses ◽  
Antibody Response ◽  
Moraxella Catarrhalis ◽  
Protein A ◽  
Serum Antibody ◽  
Age Groups ◽  
Respiratory Pathogens ◽  
Igg Antibodies ◽  
Iga Antibody

ABSTRACT Streptococcus pneumoniae and Moraxella catarrhalis are two common respiratory pathogens, colonizing as many as 54 and 72% of children, respectively, by 1 year of age. The immune responses to surface protein A of S. pneumoniae(PspA) and the high-molecular-weight outer membrane protein of M. catarrhalis (UspA) in the sera of various age groups in the general population and in the nasopharynges of 30 children monitored from birth through 1 year of age were evaluated. Immunoglobulin G (IgG) was the dominant serum antibody to PspA and UspA. Whereas the serum antibody response to PspA peaked in childhood, the antibody response to UspA peaked in adulthood. In the first 2 years of life, comparable amounts of IgM and IgG antibodies to both proteins were observed. In older persons, IgG antibodies to both antigens predominated over IgM antibodies. The levels of IgA antibody to these antigens in serum remained low during the first 2 years of life. The levels of IgM antibody to the two antigens in serum exceeded the levels of IgA antibody to the same two antigens throughout life. Although IgA was the dominant antibody to PspA and UspA in airway secretions, it was detected in a minority of the children (3 of 15 for PspA and 0 of 15 for UspA). Even the majority of the children previously colonized with these pathogens lacked antibody to them in their secretions.

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