Staphylococcus aureus types 5 and 8 capsular polysaccharide-protein conjugate vaccines - 26/08/11

Doi : 10.1016/j.ahj.2004.01.012

John B Robbins, MD ^a,^⁎ , Rachel Schneerson, MD ^a, Gary Horwith, MD ^b, Robert Naso, PhD ^b, Ali Fattom, PhD ^b

^a National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Md, USA

^b Nabi Biopharmaceuticals, Rockville, Md, USA

^* Reprint requests: John B. Robbins, National Institute of Child Health and Human Development, Bldg 6, Room 424, Bethesda, Md, 20892, USA.

Abstract

Background

Staphylococcus aureus, the first or second most common pathogen isolated from patients, is capsulated; there are at least 12 capsular types, and types 5 and 8 comprise approximately 85% of blood. Types 5 and 8, composed of a trisaccharide repeat unit including a mannose uronic acid and 2 fucoses, are non-immunogenic. As protein conjugates, they induce opsonophagoctyic antibodies that confer type-specific active and passive protection in mice.

Methods

A phase II study of patients with end-stage renal disease showed that these conjugates induced approximately one third of the immunoglobulin G antibody of healthy individuals. Increasing the dose to 100 μg of polysaccharide induced levels similar to that in healthy individuals injected with 25 μg.

Results

In a double-blinded randomized and controlled study of patients undergoing renal dialysis, the conjugates induced statistically significant protection against bacteremia for as long as 10 months after immunization. The estimated protective level was 80 μg Ab/mL. At re-injection approximately 2 years later, 83 of 83 recipients responded with protective levels.

Conclusions

Conjugate vaccine-induced antibodies to the types 5 and 8 capsular polysaccharide antibodies of S aureus prevent bacteremia caused by this pathogen. The extent and duration of conjugate-induced immunity can be extended by re-immunization approximately 1 year later. Studies of patients undergoing cardiovascular surgery who would be immunized with the staphylococcus conjugates when they are immunologically intact are planned.

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