744. The dynamics of Staphylococcus aureus carriage and comparisons by age in two studies of an investigational S aureus 4-antigen vaccine (SA4Ag)
Session: Poster Abstract Session: Vaccines: New and Novel
Thursday, October 27, 2016
Room: Poster Hall
Posters
  • Creech_ID Week Poster_Final for upload_19Oct2016.pdf (271.5 kB)
  • Background:

    SA4Ag, a vaccine under development for prevention of invasive S aureus disease, is composed of type 5 and type 8 capsular polysaccharide (CP) conjugates, clumping factor A (ClfA), and manganese transporter C (MntC). S aureus colonization is a risk factor for infection; therefore, the carriage dynamics and prevalence of specific circulating strains were assessed in two prospective SA4Ag studies.

    Methods:

    Nasal, oropharyngeal and perineal swabs were obtained at multiple time points over 12 months in two phase 1/2a studies of healthy adults aged 18 to 64 (n=284) and 65 to 85 years (n=456). The genetic relatedness of S aureus isolates was determined by multilocus sequence typing and spa typing and the diversity of ClfA and MntC variants assessed. A contemporary collection of disease isolates (n=399) from the T.E.S.T surveillance trial was also analyzed for comparison.

    Results:

    Over 12 months, 65% of younger and 48% of older adults were colonized with S aureus at any anatomical site. The distribution of clonal complexes (CCs) was similar between colonizing and disease associated isolates. Older adults were more likely to carry CC15 (23%) and CC30 (21%) isolates compared to younger adults (13% & 12%, respectively). The frequency of CP5 and CP8 isolates was similar between the younger and older age groups (CP5: 58% v. 46%; CP8: 56% vs. 61%, respectively). Analysis of ClfA variants showed high diversity and the prevalence of predominant variants (001, 002, 004, 015) varied between age groups. The 015 variant (associated with CC15) was prevalent in older adults. The most common MntC variant for both age groups was 001 (>90% of subjects).

    There were no apparent differences in S aureus colonization, acquisition, or clearance among SA4Ag and placebo recipients in either age group. Over 20% of all adults were persistent carriers from any anatomical site, typically due to the same strain.

    Conclusion:

    S aureus colonization in healthy adults is common and is characterized by significant strain diversity across age groups. Many adults were colonized with clonal types that are associated with clinical disease, and these clonal types varied by age. SA4Ag vaccination appeared to have no direct effect on the colonization dynamics of S aureus. Data were generated that can contribute to the design of studies to investigate this further.

    C. Buddy Creech, MD, MPH, FPIDS1, James Baber, MBChB, MPH2, C. Hal Jones, PhD3, Naglaa Mohamed, PhD3, Dorota Jamrozy, PhD4, Li Hao, PhD3, Matthew Holden, PhD5, Paulina Carlson, BS3, Julian Parkhill, FMedSCi6, Sharon Peacock, PhD FRCP FRCPath7, Robert W. Frenck Jr., MD, FIDSA8, Joseph M. Severs, MS9, Joseph J. Eiden, MD, PhD10, Kathrin U. Jansen, PhD10, Alejandra Gurtman, MD10 and Annaliesa S. Anderson, PhD10, (1)Vanderbilt Vaccine Research Program and Division of Pediatric Infectious Diseases, Vanderbilt University School of Medicine, Nashville, TN, (2)Vaccine Research, Pfizer Australia Pty Ltd, West Ryde, NSW, Australia, (3)Pfizer Vaccines Research and Development, Pearl River, NY, (4)The Wellcome Trust Sanger Institute, Cambridge, United Kingdom, (5)Sanger Institute, Cambridge, United Kingdom, (6)Wellcome Trust Sanger Institute, Cambridge, United Kingdom, (7)Department of Medicine, University of Cambridge, Cambridge, United Kingdom, (8)Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, (9)Vaccine Research, Pfizer Inc, Pearl River, NY, (10)Pfizer Vaccine Research, Pearl River, NY

    Disclosures:

    C. B. Creech, Pfizer: Collaborator and Investigator , Consulting fee and Research support

    J. Baber, Pfizer: Employee and Shareholder , Salary

    C. H. Jones, Pfizer: Employee and Shareholder , Salary

    N. Mohamed, Pfizer: Employee and Shareholder , Salary

    D. Jamrozy, None

    L. Hao, Pfizer: Employee and Shareholder , Salary

    M. Holden, Pfizer: Consultant , Consulting fee

    P. Carlson, Pfizer: Employee and Shareholder , Salary

    J. Parkhill, None

    S. Peacock, None

    R. W. Frenck Jr., Pfizer: Investigator , Research support

    J. M. Severs, Pfizer: Employee and Shareholder , Salary

    J. J. Eiden, Pfizer, Inc: Employee , Salary

    K. U. Jansen, Pfizer, Inc: Employee and Shareholder , Salary

    A. Gurtman, Pfizer: Employee and Shareholder , Salary

    A. S. Anderson, Pfizer, Inc: Employee , Salary

    Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.