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.
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.
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.
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. B. Creech,
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