677. An Investigation of Genes Encoding Potential Vaccine Targets Across Genetically Unrelated Pediatric Clinical Streptococcus pneumoniae Isolates in the Post Pneumococcal Conjugate Vaccine Era
Session: Oral Abstract Session: Pneumococcal Vaccine for All Ages
Friday, October 4, 2013: 10:45 AM
Room: The Moscone Center: 200-212
Background: Several virulence genes encoding proteins have been suggested as potential vaccine candidates for protection against either pneumococcal carriage or invasive disease. The distribution of these genes across serotypes and genotypes has not been analyzed, following the introduction of the pneumococcal conjugate vaccines (PCV7 and 13). Our study sought virulence genes commonly found in isolates recovered from children in the post-PCV era. 

Methods: Fifteen pneumococcal genes were selected. Sixty clinical S. pneumoniae isolates from 2001-2012 were selected from our collection; 92% of isolates were obtained post 2007. 49 non-PCV13 and 11 PCV13 serotypes were chosen to maximize the genetic variation among strains and included internationally recognized clones and sequence types (STs) observed among several serotypes. DNA was extracted. Multilocus sequence typing (MLST) was performed. Presence of genes was detected by polymerase chain reaction using primers designed from published sequences.

Results: Forty-nine non-PCV13 isolates included serotypes 7C, 8, 10, 11, 12F, 13, 15A, 15B, 15C, 16, 17, 18A, 21, 22F, 23A, 23B, 24, 31, 33A, 33F, 34, 35B, 38, and 4 nontypeable (NT) strains. Eleven PCV13 isolates included serotypes 3, 6A, 18C, 19A, 19F, and 23F. Six genes were present across all strains including the NT S. pneumoniae, while cbpA, lytA, pspA and rrgC were present in less than 25% of the isolates (Table). Genomic diversity was evident by MLST, by which 47 STs were identified.
Gene target(n=15) PCR-positive (n=60)
pcsB, potD, pppA,sp2108, sp0148, stkP 60 (100%)
nanA, pia, plyA, psaA 56-59 (93-98%)
phtA 36 (60%)
cbpA, lytA 9-13 (15-22%)
pspA, rrgC 4-6 (7-10%)

Conclusion: This study identified 6 genes encoding potential vaccine candidates that were present in both classic and NT S. pneumoniae representing a wide variety of genotypes. Expanded studies on the prevalence of specific genetic components across a larger number of isolates and genotypes will provide knowledge necessary to select candidates that maximize coverage against pneumococcal isolates.

Kristina G. Hulten, PhD1, Edward O. Mason, PhD1, Linda B. Lamberth, BS1, William J. Barson, MD2, Philana L. Lin, MD, MSc3, Jose R. Romero, MD4, John S. Bradley, MD, FIDSA5, Tina Q. Tan, MD6, Laurence B. Givner, MD7, Jill A. Hoffman, MD8, John M. Mclaughlin, PhD, MSPH9, Stephen Kagan, MD, FACP9 and Sheldon L. Kaplan, MD, FIDSA1, (1)Baylor College of Medicine and Texas Children's Hospital, Houston, TX, (2)Nationwide Children's Hospital and The Ohio State University College of Medicine, Columbus, OH, (3)Children's Hospital of Pittsburgh, Pittsburgh, PA, (4)University of Arkansas for Medical Sciences, Little Rock, AR, (5)Rady Children's Hospital - San Diego, San Diego, CA, (6)Northwestern University Feinberg School of Medicine, Chicago, IL, (7)Wake Forest University School of Medicine, Winston-Salem, NC, (8)Children's Hospital, Los Angeles, Los Angeles, CA, (9)Pfizer Specialty Care Medicines Development Group, Collegeville, PA


K. G. Hulten, Pfizer : Collaborator, Research support

E. O. Mason, None

L. B. Lamberth, None

W. J. Barson, None

P. L. Lin, None

J. R. Romero, None

J. S. Bradley, None

T. Q. Tan, None

L. B. Givner, None

J. A. Hoffman, None

J. M. Mclaughlin, Pfizer, Inc.: Employee and Shareholder, Salary

S. Kagan, Pfizer, Inc.: Employee and Shareholder, Salary

S. L. Kaplan, Pfizer: Research Contractor,

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