In vivo screen of genetically conserved Streptococcus pneumoniae proteins for protective immunogenicity.
We evaluated 52 different E. coli expressed pneumococcal proteins as immunogens in a BALB/c mouse model of S. pneumoniae lung infection. Proteins were selected based on genetic conservation across disease-causing serotypes and bioinformatic prediction of antibody binding to the target antigen. Seven proteins induced protective responses, in terms of reduced lung burdens of the serotype 3 pneumococci. Three of the protective proteins were histidine triad protein family members (PhtB, PhtD and PhtE). Four other proteins, all bearing LPXTG linkage domains, also had activity in this model (PrtA, NanA, PavB and Eng). PrtA, NanA and Eng were also protective in a CBA/N mouse model of lethal pneumococcal infection. Despite data inferring widespread genomic conservation, flow-cytometer based antisera binding studies confirmed variable levels of antigen expression across a panel of pneumococcal serotypes. Finally, BALB/c mice were immunized and intranasally challenged with a viulent serotype 8 strain, to help understand the breadth of protection. Those mouse studies reaffirmed the effectiveness of the histidine triad protein grouping and a single LPXTG protein, PrtA.
Vaccine Immunotherapeutics, Pfizer, 10777 Science Center Drive, La Jolla, CA 92121, USA.
Richard J
RJ
Anderson
Vaccine Immunotherapeutics, Pfizer, 10777 Science Center Drive, La Jolla, CA 92121, USA.
Siradanahalli
S
Guru
Vaccine Immunotherapeutics, Pfizer, 200-340 Terry Fox Drive, Ottawa, Ontario K2K3A2, Canada.
Risini
R
Weeratna
Vaccine Immunotherapeutics, Pfizer, 200-340 Terry Fox Drive, Ottawa, Ontario K2K3A2, Canada.
Shawn
S
Makinen
Vaccine Immunotherapeutics, Pfizer, 10777 Science Center Drive, La Jolla, CA 92121, USA.
Derek J
DJ
Falconer
Vaccine Immunotherapeutics, Pfizer, 10777 Science Center Drive, La Jolla, CA 92121, USA.
Neil C
NC
Sheppard
Vaccine Immunotherapeutics, Pfizer, 10777 Science Center Drive, La Jolla, CA 92121, USA.
Susanne
S
Lang
Vaccine Immunotherapeutics, Pfizer, 10777 Science Center Drive, La Jolla, CA 92121, USA.
Bingsheng
B
Chang
Vaccine Immunotherapeutics, Pfizer, 10777 Science Center Drive, La Jolla, CA 92121, USA.
Anne-Laure
AL
Goenaga
Vaccine Research & Development, Pfizer, 401 North Middletown Road, Pearl River, NY 10965, USA.
Bruce A
BA
Green
Vaccine Immunotherapeutics, Pfizer, 10777 Science Center Drive, La Jolla, CA 92121, USA.
James R
JR
Merson
Vaccine Immunotherapeutics, Pfizer, 10777 Science Center Drive, La Jolla, CA 92121, USA.
Stephen J
SJ
Gracheck
Vaccine Immunotherapeutics, Pfizer, 10777 Science Center Drive, La Jolla, CA 92121, USA. Electronic address: Jim.eyles@pfizer.com.
Jim E
JE
Eyles
D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D003001:Cloning, Molecular; D019295:Computational Biology; D017124:Conserved Sequence; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D015870:Gene Expression; D005820:Genetic Testing; D008168:Lung / Q000382:microbiology; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D011018:Pneumonia, Pneumococcal / Q000382:microbiology / Q000517:prevention & control*; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000276:immunology*; D016019:Survival Analysis
D000942:Antigens, Bacterial; D001426:Bacterial Proteins
Antibody; Antigen; Immunity; Pneumococcal; Pneumococcus; Vaccine