Immunity to Staphylococcus aureus: Implications for Vaccine Development

2019 ◽  
pp. 766-775
Author(s):  
Richard A. Proctor
Keyword(s):  
Staphylococcus Aureus ◽  
Vaccine Development

scholarly journals CD4 T Cell Antigens from Staphylococcus aureus Newman Strain Identified following Immunization with Heat-Killed Bacteria

2012 ◽  
Vol 19 (4) ◽  
pp. 477-489 ◽  
Author(s):  
Paulraj K. Lawrence ◽  
Bachra Rokbi ◽  
Nadège Arnaud-Barbe ◽  
Eric L. Sutten ◽  
Junzo Norimine ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
T Cell ◽  
Reverse Genetics ◽  
Vaccine Development ◽  
Protein A ◽  
Cd4 T Cell ◽  
Content Type ◽  
Intramammary Infections ◽  
T Cell Antigens ◽  
Ifn Γ

ABSTRACTStaphylococcus aureusis a commensal bacterium associated with the skin and mucosal surfaces of humans and animals that can also cause chronic infection. The emergence of antibiotic-resistant strains such as methicillin-resistantS. aureus(MRSA) and strains causing chronic intramammary infections (IMI) in cows results in severe human and livestock infections. Conventional approaches to vaccine development have yielded only a few noneffective vaccines against MRSA or IMI strains, so there is a need for improved vaccine development. CD4 T lymphocytes are required for promoting gamma interferon (IFN-γ) mediated immunoglobulin isotype switching in B lymphocytes to produce high-affinity IgG antibodies and IFN-γ-mediated phagocyte activation for an effective resolution of bacterial infection. However, the lack of known CD4 T cell antigens fromS. aureushas made it difficult to design effective vaccines. The goal of this study was to identifyS. aureusproteins recognized by immune CD4 T cells. Using a reverse genetics approach, 43 antigens were selected from theS. aureusNewman strain. These included lipoproteins, proteases, transcription regulators, an alkaline shock protein, conserved-domain proteins, hemolysins, fibrinogen-binding protein, staphylokinase, exotoxin, enterotoxin, sortase, and protein A. Screening of expressed proteins for recall T cell responses in outbred, immune calves identified 13 proteins that share over 80% sequence identity among MRSA or IMI strains. These may be useful for inclusion in a broadly protective multiantigen vaccine against MRSA or IMI.

scholarly journals Application of Median Lethal Concentration (LC50) of Pathogenic Microorganisms and Their Antigens in Vaccine Development

2020 ◽  
Author(s):  
Saganuwan Alhaji Saganuwan
Keyword(s):  
Staphylococcus Aureus ◽  
Disease Virus ◽  
Vaccine Development ◽  
Hepatitis A Virus ◽  
Lethal Dose ◽  
Vaccine Dose ◽  
Foot And Mouth Disease ◽  
Bacterial Colony ◽  
Mouth Disease Virus

Abstract Objective: Lack of ideal mathematical models to qualify and quantify both pathogenicity, and virulence is a dreadful setback in development of new antimicrobials and vaccines against resistance pathogenic microorganisms.Hence, the modified arithmetical formula of Reed and Muenchhas been integrated with other formulas and used to determine bacterial colony forming unit/ viral concentration, virulence and immunogenicity from LC50s established in the laboratories. Results: Microorganisms’antigens tested are Staphylococcus aureus, Streptococcuspneumonia, Pseudomonas aeruginosa in mice and rat, Edwardsiellaictaluri, Aeromonashydrophila, Aeromonasveronii in fish, New Castle Disease virus in chicken, Sheep Pox Virus, Foot-and-Mouth Disease Virus and Hepatitis A virus in vitro, respectively. The LC50s for the pathogens using different routes of administrations are 1.93 x 103(sheep poxvirus) and 1.75 x 1010 for Staphylococcus aureus (ATCC29213) in rat respectively. Titre index (TI) equals N log10 LC50 and provides protection against lethal dose in graded fashion which translates to protection index. N is the number of vaccine dose that could neutralize the LC50. Hence, parasite inoculum of 103 to 1011could be used as basis for determination of median lethal dose(LD50), LC50 and median bacterial concentrations (BC50)determination, pathogenic dose for immune stimulation should be sought at concentrations less than LC10.

scholarly journals Determination of Median Lethal Concentrations (Lc50) of Pathogenic Antigens and Their Applications in Vaccine Development

2020 ◽  
Author(s):  
Saganuwan Alhaji Saganuwan
Keyword(s):  
Staphylococcus Aureus ◽  
Disease Virus ◽  
Vaccine Development ◽  
Hepatitis A Virus ◽  
Lethal Dose ◽  
Vaccine Dose ◽  
Foot And Mouth Disease ◽  
Mouth Disease Virus

Abstract Objective: Lack of ideal mathematical models to qualify and quantify both pathogenicity, and virulence is a dreadful setback in development of new antimicrobials and vaccines against resistance pathogenic microorganisms. Hence, the modified arithmetical formula of Reed and Muench has been integrated with other formulas and used for determination of antigen concentration and parasites inoculums that would kill 50% of test animals (LC50).Results: Microorganisms’ antigens tested are Staphylococcus aureus, Streptococcus pneumonia, Pseudomonas aeruginosa in mice and rat, Edwardsiella ictaluri, Aeromonas hydrophila, Aeromonas veronii in fish, New Castle Disease virus in chicken, Sheep Pox Virus, Foot-and-Mouth Disease Virus and Hepatitis A virus in vitro, respectively. The LC50s for the pathogens using different routes of administrations are 1.93 x 103 (sheep poxvirus) and 1.75 x 1010 for Staphylococcus aureus (ATCC29213) in rat respectively. N is the number of vaccine dose that could neutralize the LC50.Titre index (TI) equals N log10 LC50 and provides protection against lethal dose in graded fashion which translates to protection index. Hence, parasite inoculum of 103 to 1011 could be used as basis for median lethal dose (LD50), LC50 and median bacterial concentrations (BC50) determination, pathogenic dose for immune stimulation should be sought at concentrations less than LC10.

Identification of secreted and cellular antigens of Staphylococcus aureus causing dairy sheep mastitis and their potential for vaccine development

2020 ◽  
Vol 230 ◽  
pp. 110149
Author(s):  
Carla Maria Longheu ◽  
Elisa Azara ◽  
Gavino Marogna ◽  
Maria Filippa Addis ◽  
Sebastiana Tola
Keyword(s):  
Staphylococcus Aureus ◽  
Vaccine Development ◽  
Dairy Sheep

scholarly journals Staphylococcus aureus—A Known Opponent against Host Defense Mechanisms and Vaccine Development—Do We Still Have a Chance to Win?

2022 ◽  
Vol 23 (2) ◽  
pp. 948
Author(s):  
Urszula Wójcik-Bojek ◽  
Barbara Różalska ◽  
Beata Sadowska
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Therapy ◽  
Virulence Factors ◽  
Host Defense ◽  
Defense Mechanisms ◽  
Vaccine Development ◽  
Global Trends ◽  
Molecular Microbiology ◽  
Modern Technologies ◽  
New Vaccines

The main purpose of this review is to present justification for the urgent need to implement specific prophylaxis of invasive Staphylococcus aureus infections. We emphasize the difficulties in achieving this goal due to numerous S. aureus virulence factors important for the process of infection and the remarkable ability of these bacteria to avoid host defense mechanisms. We precede these considerations with a brief overview of the global necessitiy to intensify the use of vaccines against other pathogens as well, particularly in light of an impasse in antibiotic therapy. Finally, we point out global trends in research into modern technologies used in the field of molecular microbiology to develop new vaccines. We focus on the vaccines designed to fight the infections caused by S. aureus, which are often resistant to the majority of available therapeutic options.

scholarly journals Application of Median Lethal Concentration (LC50) of Pathogenic Microorganisms and Their Antigens in Vaccine Development

2020 ◽  
Author(s):  
Saganuwan Alhaji Saganuwan
Keyword(s):  
Staphylococcus Aureus ◽  
Disease Virus ◽  
Vaccine Development ◽  
Hepatitis A Virus ◽  
Lethal Dose ◽  
Vaccine Dose ◽  
Pathogenic Microorganisms ◽  
Bacterial Colony ◽  
Mouth Disease Virus

Abstract Objective: Lack of ideal mathematical models to qualify and quantify both pathogenicity, and virulence is a dreadful setback in development of new antimicrobials and vaccines against resistance pathogenic microorganisms. Hence, the modified arithmetical formula of Reed and Muench has been integrated with other formulas and used to determine bacterial colony forming unit/ viral concentration, virulence and immunogenicity. Results: Microorganisms’antigens tested are Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa in mice and rat, Edwardsiella ictaluri, Aeromonas hydrophila, Aeromonas veronii in fish, New Castle Disease virus in chicken, Sheep Pox Virus, Foot-and-Mouth Disease Virus and Hepatitis A virus in vitro, respectively. The LC50s for the pathogens using different routes of administrations are 1.93 x 103(sheep poxvirus) and 1.75 x 1010 for Staphylococcus aureus (ATCC29213) in rat respectively. Titer index (TI) equals N log10 LC50 and provides protection against lethal dose in graded fashion which translates to protection index. N is the number of vaccine dose that could neutralize the LC50. Hence, parasite inoculum of 103 to 1011may be used as basis for determination of LC50 and median bacterial concentrations (BC50).Pathogenic dose for immune stimulation should be sought at concentration about LC10.

scholarly journals Staphylococcus aureus Alpha-Toxin Is Conserved among Diverse Hospital Respiratory Isolates Collected from a Global Surveillance Study and Is Neutralized by Monoclonal Antibody MEDI4893

2016 ◽  
Vol 60 (9) ◽  
pp. 5312-5321 ◽  
Author(s):  
David E. Tabor ◽  
Li Yu ◽  
Hoyin Mok ◽  
Christine Tkaczyk ◽  
Bret R. Sellman ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Monoclonal Antibody ◽  
Vaccine Development ◽  
Geographic Location ◽  
The United States ◽  
Geographic Region ◽  
Alpha Toxin ◽  
Content Type ◽  
Gene Sequence Analysis ◽  
The Subject

ABSTRACTStaphylococcus aureusinfections lead to an array of illnesses ranging from mild skin infections to serious diseases, such endocarditis, osteomyelitis, and pneumonia. Alpha-toxin (Hla) is a pore-forming toxin, encoded by thehlagene, that is thought to play a key role inS. aureuspathogenesis. A monoclonal antibody targeting Hla, MEDI4893, is in clinical development for the prevention ofS. aureusventilator-associated pneumonia (VAP). The presence of thehlagene and Hla protein in 994 respiratory isolates collected from patients in 34 countries in Asia, Europe, the United States, Latin America, the Middle East, Africa, and Australia was determined. Hla levels were correlated with the geographic location, age of the subject, and length of stay in the hospital.hlagene sequence analysis was performed, and mutations were mapped to the Hla crystal structure.S. aureussupernatants containing Hla variants were tested for susceptibility or resistance to MEDI4893. Thehlagene was present and Hla was expressed in 99.0% and 83.2% of the isolates, respectively, regardless of geographic region, hospital locale, or age of the subject. More methicillin-susceptible than methicillin-resistant isolates expressed Hla (86.9% versus 78.8%;P= 0.0007), andS. aureusisolates from pediatric patients expressed the largest amounts of Hla. Fifty-seven different Hla subtypes were identified, and 91% of the isolates encoded an Hla subtype that was neutralized by MED4893. This study demonstrates that Hla is conserved in diverseS. aureusisolates from around the world and is an attractive target for prophylactic monoclonal antibody (MAb) or vaccine development.

scholarly journals Exploring Staphylococcus aureus pathways to disease for vaccine development

2011 ◽  
Vol 34 (2) ◽  
pp. 317-333 ◽  
Author(s):  
Andrea DeDent ◽  
Hwan Keun Kim ◽  
Dominique Missiakas ◽  
Olaf Schneewind
Keyword(s):  
Staphylococcus Aureus ◽  
Vaccine Development
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