Persistence of Immune Responses Through 36 Months in Healthy Adults After Vaccination With a Novel Staphylococcus aureus 4-Antigen Vaccine (SA4Ag).

Autor: Creech CB; Vanderbilt University School of Medicine and the Monroe Carell Jr. Children's Hospital, Nashville, Tennessee, USA., Frenck RW; Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA., Fiquet A; Pfizer Vaccines Research & Development, Hurley, Berkshire, UK., Feldman R; QPS-MRA, Miami Research Associates LLC, Miami, Florida, USA., Kankam MK; Vince and Associates Clinical Research, Overland Park, Kansas, USA., Pathirana S; Pfizer Vaccines Research & Development, Pearl River, New York, USA., Baber J; Pfizer Vaccines Research & Development, Sydney, New South Wales, Australia., Radley D; Pfizer Vaccines Research & Development, Pearl River, New York, USA., Cooper D; Pfizer Vaccines Research & Development, Pearl River, New York, USA., Eiden J; Pfizer Vaccines Research & Development, Pearl River, New York, USA., Gruber WC; Pfizer Vaccines Research & Development, Pearl River, New York, USA., Jansen KU; Pfizer Vaccines Research & Development, Pearl River, New York, USA., Anderson AS; Pfizer Vaccines Research & Development, Pearl River, New York, USA., Gurtman A; Pfizer Vaccines Research & Development, Pearl River, New York, USA.
Jazyk: angličtina
Zdroj: Open forum infectious diseases [Open Forum Infect Dis] 2019 Dec 24; Vol. 7 (1), pp. ofz532. Date of Electronic Publication: 2019 Dec 24 (Print Publication: 2020).
DOI: 10.1093/ofid/ofz532
Abstrakt: Background: Staphylococcus aureus causes serious health care- and community-associated disease, requiring improved preventive measures such as vaccines. The investigational S. aureus 4-antigen vaccine (SA4Ag), comprising capsular polysaccharide serotypes 5 and 8 (CP5 and CP8) conjugated to CRM 197 , recombinant mutant clumping factor A (r m ClfA), and recombinant manganese transporter protein C (rP305A or rMntC), was well tolerated, inducing robust functional immune responses to all 4 antigens through 12 months postvaccination. This is a serological extension study through 36 months postvaccination.
Methods: In 2 previous studies, healthy adults received SA4Ag, SA3Ag (without rMntC), or placebo; serology was also assessed at ~24 and ~36 months postvaccination. Functional immune responses (antibody responses that facilitate killing of S. aureus or neutralize S. aureus virulence mechanisms) were assessed with opsonophagocytic activity killing assays (CP5 or CP8) and a fibrinogen-binding inhibition assay (ClfA). A competitive Luminex immunoassay assessed ClfA and rMntC responses. Adverse events within 48 hours of blood draw were recorded.
Results: Four hundred forty subjects (18-64 years old, 255; 65-85 years old, 185) were enrolled. At 24 and 36 months postvaccination, subjects receiving SA4Ag had substantially higher geometric mean titers (GMTs) for CP5, CP8, and ClfA vs baseline; geometric mean fold rises (GMFRs) from baseline to month 36 were 2.7-8.1. For rMntC, 36-month GMTs declined from peak levels but remained above baseline for all SA4Ag groups; GMFRs from baseline to month 36 were 1.8 and 1.5 in the younger and older cohorts, respectively.
Conclusions: Persistent functional immune responses to S. aureus antigens were observed through 36 months in healthy adults.
Clinicaltrialsgov: NCT01643941 and NCT01364571.
(© The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
Databáze: MEDLINE
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