Meningococcal surrogates of protection?serum bactericidal antibody activity

Vaccine ◽  
2005 ◽  
Vol 23 (17-18) ◽  
pp. 2222-2227 ◽  
Author(s):  
R BORROW ◽  
P BALMER ◽  
E MILLER
Keyword(s):  
Antibody Activity ◽  
Bactericidal Antibody

scholarly journals A recombinant commensal bacteria elicits heterologous antigen-specific immune responses during pharyngeal carriage

2021 ◽  
Vol 13 (601) ◽  
pp. eabe8573
Author(s):  
Jay R. Laver ◽  
Diane Gbesemete ◽  
Adam P. Dale ◽  
Zoe C. Pounce ◽  
Carl N. Webb ◽  
...  
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
Pathogenic Bacteria ◽  
Plasma Cells ◽  
Memory B Cells ◽  
Vaccine Antigen ◽  
Antibody Activity ◽  
Heterologous Antigen ◽  
Bactericidal Antibody ◽  
Specific Igg

The human nasopharynx contains a stable microbial ecosystem of commensal and potentially pathogenic bacteria, which can elicit protective primary and secondary immune responses. Experimental intranasal infection of human adults with the commensal Neisseria lactamica produced safe, sustained pharyngeal colonization. This has potential utility as a vehicle for sustained release of antigen to the human mucosa, but commensals in general are thought to be immunologically tolerated. Here, we show that engineered N. lactamica, chromosomally transformed to express a heterologous vaccine antigen, safely induces systemic, antigen-specific immune responses during carriage in humans. When the N. lactamica expressing the meningococcal antigen Neisseria Adhesin A (NadA) was inoculated intranasally into human volunteers, all colonized participants carried the bacteria asymptomatically for at least 28 days, with most (86%) still carrying the bacteria at 90 days. Compared to an otherwise isogenic but phenotypically wild-type strain, colonization with NadA-expressing N. lactamica generated NadA-specific immunoglobulin G (IgG)– and IgA-secreting plasma cells within 14 days of colonization and NadA-specific IgG memory B cells within 28 days of colonization. NadA-specific IgG memory B cells were detected in peripheral blood of colonized participants for at least 90 days. Over the same period, there was seroconversion against NadA and generation of serum bactericidal antibody activity against a NadA-expressing meningococcus. The controlled infection was safe, and there was no transmission to adult bedroom sharers during the 90-day period. Genetically modified N. lactamica could therefore be used to generate beneficial immune responses to heterologous antigens during sustained pharyngeal carriage.

scholarly journals Cloning and Expression of the Moraxella catarrhalis Lactoferrin Receptor Genes

1998 ◽  
Vol 66 (8) ◽  
pp. 3656-3665 ◽  
Author(s):  
Run-Pan Du ◽  
Qijun Wang ◽  
Yan-Ping Yang ◽  
Anthony B. Schryvers ◽  
Pele Chong ◽  
...  
Keyword(s):  
Moraxella Catarrhalis ◽  
Vaccine Candidate ◽  
Bacterial Species ◽  
Protein A ◽  
Cloning And Expression ◽  
Gene Arrangement ◽  
Antibody Activity ◽  
Reading Frame ◽  
Lactoferrin Receptor ◽  
Bactericidal Antibody

ABSTRACT The lactoferrin receptor genes from two strains of Moraxella catarrhalis have been cloned and sequenced. The lfrgenes are arranged as lbpB followed by lbpA, a gene arrangement found in lactoferrin and transferrin receptor operons from several bacterial species. In addition, a third open reading frame, orf3, is located one nucleotide downstream oflbpA. The deduced lactoferrin binding protein A (LbpA) sequences from the two strains were found to be 99% identical, the LbpB sequences were 92% identical, and the ORF3 proteins were 98% identical. The lbpB gene was PCR amplified and sequenced from a third strain of M. catarrhalis, and the encoded protein was found to be 77% identical and 84% similar to the other LbpB proteins. Recombinant LbpA and LbpB proteins were expressed fromEscherichia coli, and antisera raised to the purified proteins were used to assess antigenic conservation in a panel ofM. catarrhalis strains. The recombinant proteins were tested for the ability to bind human lactoferrin following gel electrophoresis and electroblotting, and rLbpB, but not rLbpA, was found to bind lactoferrin. Bactericidal antibody activity was measured, and while the anti-rLbpA antiserum was not bactericidal, the anti-rLbpB antisera were found to be weakly bactericidal. Thus, LbpB may have potential as a vaccine candidate.

scholarly journals Transient IgA-lambda paraproteinemia during treatment of acute myelomonoblastic leukemia

Blood ◽  
1980 ◽  
Vol 55 (1) ◽  
pp. 21-25 ◽  
Author(s):  
B Van Camp ◽  
P Reynaerts ◽  
JP Naets ◽  
J Radl
Keyword(s):  
Bone Marrow ◽  
Cell Proliferation ◽  
Clonal Expansion ◽  
Cellular Level ◽  
Light Chains ◽  
Antibody Activity ◽  
Intensive Chemotherapy ◽  
Bone Marrow Aplasia ◽  
Large Panel ◽  
Common Antigens

Abstract Monoclonal plasma cell proliferation with secretion of IgA-lambda and free lambda light chains during a phase of bone marrow aplasia following intensive chemotherapy was observed in a patient suffering from acute myelomonoblastic leukemia. The clonal expansion and regression was investigated at the cellular level by immunofluorescence using an antiserum against the idiotype of the paraportein. Although a large panel of common antigens was used for testing, no antibody activity of the paraprotein could be demonstrated.

Sequential studies of melanoma leukocyte-dependent antibody activity in melanoma patients

1978 ◽  
Vol 14 (6) ◽  
pp. 629-637 ◽  
Author(s):  
P. Hersey ◽  
A.E. Edwards ◽  
E. Murray ◽  
W.H. McCarthy ◽  
G.W. Milton
Keyword(s):  
Antibody Activity ◽  
Melanoma Patients ◽  
Sequential Studies

scholarly journals The identification of novel immunogenic antigens as potential Shigella vaccine components

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Ruklanthi de Alwis ◽  
Li Liang ◽  
Omid Taghavian ◽  
Emma Werner ◽  
Hao Chung The ◽  
...  
Keyword(s):  
Core Genome ◽  
Genomic Analysis ◽  
Carrier Proteins ◽  
Vaccine Candidates ◽  
Vaccine Antigens ◽  
Bactericidal Antibody ◽  
In Vivo Testing ◽  
Species Specific ◽  
Selection Of

Abstract Background Shigella is a major diarrheal pathogen for which there is presently no vaccine. Whole genome sequencing provides the ability to predict and derive novel antigens for use as vaccines. Here, we aimed to identify novel immunogenic Shigella antigens that could serve as Shigella vaccine candidates, either alone, or when conjugated to Shigella O-antigen. Methods Using a reverse vaccinology approach, where genomic analysis informed the Shigella immunome via an antigen microarray, we aimed to identify novel immunogenic Shigella antigens. A core genome analysis of Shigella species, pathogenic and non-pathogenic Escherichia coli, led to the selection of 234 predicted immunogenic Shigella antigens. These antigens were expressed and probed with acute and convalescent serum from microbiologically confirmed Shigella infections. Results Several Shigella antigens displayed IgG and IgA seroconversion, with no difference in sero-reactivity across by sex or age. IgG sero-reactivity to key Shigella antigens was observed at birth, indicating transplacental antibody transfer. Six antigens (FepA, EmrK, FhuA, MdtA, NlpB, and CjrA) were identified in in vivo testing as capable of producing binding IgG and complement-mediated bactericidal antibody. Conclusions These findings provide six novel immunogenic Shigella proteins that could serve as candidate vaccine antigens, species-specific carrier proteins, or targeted adjuvants.

scholarly journals 10. Kinetics of Post-Vaccination Seroprotection to S. Pneumonia for the Immune-Compromised and Vaccine-Naïve Populations

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S27-S28
Author(s):  
Jeffrey Gruenglas ◽  
James Mond ◽  
Micaela Scobie ◽  
Cynthia Tolman ◽  
Joseph Martinez
Keyword(s):  
Capsular Polysaccharide ◽  
The Elderly ◽  
Community Acquired Pneumonia ◽  
Prior History ◽  
Antibody Activity ◽  
Vaccine Response ◽  
Serum Samples ◽  
Opsonic Activity ◽  
And Control

Abstract Background S. pneumonia infection presents a significant challenge, accounting for 20–38% of hospital-acquired pneumonia, and the leading cause of community-acquired pneumonia despite availability of effective vaccines. Incidence is highest in children under 2 years, the immunocompromised, and elderly. CDC has reported the emergence of antibiotic resistance in ~30% of cases, adding to risk of morbidity and mortality. Fewer than half of the elderly are vaccinated and vulnerable to infection on admission. Passive immunotherapy as an adjunct to vaccines may improve outcomes in such populations. The objective of this study was to evaluate whether seroprotective response induced with a pneumococcal conjugate vaccine could rapidly yield protective opsonic levels of antibody within anticipated duration of hospitalization. Methods Healthy donors (n=30) were immunized with Prevnar. Blood was drawn on days 0, 3, 7, 10, 14, 21, and 28. Samples were pooled and tested for presence of functional opsonic antibodies recognizing capsular polysaccharides. Clearance mechanism of S. pneumonia was based on antibody recognition to pneumococcal capsular polysaccharide and opsonic titers used as an in vitro surrogate to evaluate the efficacy of vaccine. Results There was little to no opsonic activity against most serotypes on day 0, except for low antibody activity with serotypes 1, 3, 4, and 5. Titers increased, with protective levels achieved by day 10 for most serotypes (except 14 and 18C), peaking at day 14 or after across serotypes (Figures 1 and 2). Average titers rose from log2 titer 2 on day 0 to log2 titer 8 on days 21 and 28. Titers against most serotypes reached log2 10 (titer 1024) or higher. Patients remained susceptible to nosocomial infection for at least 10 days post admission until protective titers are reached. OPK titers (log2 scale) for serum samples on day 0 (pre), day 3, 7, 10, 14, 21, 28, and control for S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V. N=2. OPK titers (log2 scale) for serum samples on day 0 (pre), day 3, 7, 10, 14, 21, 28, and control for S. pneumoniae serotypes 14, 18C, 19A, 19F, and 23F. N=2. Conclusion Patients with no prior history of vaccination (or inability to mount response) with Prevnar or pneumovax remain vulnerable to S. pneumonia infection even if vaccinated on entry, due to delayed kinetics in reaching protective titers. These patients may require prophylactic intervention of hyperimmune Ig with high opsonic titers to S. pneumonia, providing protection until vaccine response elicits protective antibodies. Disclosures All Authors: No reported disclosures

scholarly journals Design of a companion bioinformatic tool to detect the emergence and geographical distribution of SARS-CoV-2 Spike protein genetic variants

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Alice Massacci ◽  
Eleonora Sperandio ◽  
Lorenzo D’Ambrosio ◽  
Mariano Maffei ◽  
Fabio Palombo ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Consensus Sequence ◽  
Cell Epitope ◽  
Vaccine Design ◽  
Binding Domain ◽  
Spike Protein ◽  
Antibody Activity ◽  
Binding Motif ◽  
Receptor Binding Domain ◽  
The Impact

Abstract Background Tracking the genetic variability of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) is a crucial challenge. Mainly to identify target sequences in order to generate robust vaccines and neutralizing monoclonal antibodies, but also to track viral genetic temporal and geographic evolution and to mine for variants associated with reduced or increased disease severity. Several online tools and bioinformatic phylogenetic analyses have been released, but the main interest lies in the Spike protein, which is the pivotal element of current vaccine design, and in the Receptor Binding Domain, that accounts for most of the neutralizing the antibody activity. Methods Here, we present an open-source bioinformatic protocol, and a web portal focused on SARS-CoV-2 single mutations and minimal consensus sequence building as a companion vaccine design tool. Furthermore, we provide immunogenomic analyses to understand the impact of the most frequent RBD variations. Results Results on the whole GISAID sequence dataset at the time of the writing (October 2020) reveals an emerging mutation, S477N, located on the central part of the Spike protein Receptor Binding Domain, the Receptor Binding Motif. Immunogenomic analyses revealed some variation in mutated epitope MHC compatibility, T-cell recognition, and B-cell epitope probability for most frequent human HLAs. Conclusions This work provides a framework able to track down SARS-CoV-2 genomic variability.

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