Vaccine formulations comprising saponin-containing adjuvants

摘要

The present invention provides for a novel oil-in-water (O/W) emulsion, with increased stability in the presence of bacterial or viral suspensions, especially those concentrated and non-purified (crude extracts) or minimally purified. The emulsion of the present invention can act as vehicle for the delivery of a pharmaceutical composition comprising at least one immunogen and, in particular, an immunogen selected from the group consisting of an inactivated pathogen, an attenuated pathogen, a subunit, a recombinant expression vector, and a plasmid or combinations thereof.

主权项

1. A safe and effective stable immunological injectable oil-in-water (O/W) emulsion, wherein the emulsion is effective for eliciting an immunologic response in a vaccinate, comprising:
(i) an aqueous solution comprising about 60 μg of whole inactivated porcine circovirus 2 (PCV2) virus per dose; (ii) an aqueous solution comprising a saponin in the amount of about 0.7 mg/dose to about 1.3 mg/dose; wherein the saponin consists of an anion-exchange column purified extract of Quillaja saponaria Molina bark enriched for QS-17, QS-18 and QS-21; (iii) an aqueous solution comprising aluminum hydroxide in the amount of about 0.37% w/v to about 0.42% w/v of the emulsion; (iv) paraffin oil present in the amount of about 20% to about 40% of the emulsion; (v) a non-ionic lipophilic surfactant, present in the amount of 0.1% to about 2.5% w/v of the emulsion, and selected from sorbitan fatty acid monoesters, fatty acid esters of mannide, ethoxylated fatty acid esters of mannide, and combinations thereof; (vi) a non-ionic hydrophilic surfactant present in the amount of 0.1% to about 1.5% w/v of the emulsion, and having a high hydrophilic-lipophilic balance (HLB) value between 13 and 40 selected from ethoxylated fatty acid monoesters of sorbitan, ethoxylated fatty acids, and combinations thereof; and (vii) a non-ionic hydrophilic surfactant present in the amount of about 1% to about 8% w/v of the emulsion, and having a low hydrophilic-lipophilic balance (HLB) value between 9 and 13 selected from ethoxylated fatty acid triesters of sorbitan, ethoxylated fatty acid diesters of sorbitan, ethoxylated fatty acid monoesters of sorbitan, ethoxylated fatty acids, ethoxylated castor oil and, combinations thereof; and wherein the final HLB of the emulsion is from about 9 to about 12; and wherein the emulsion remains an O/W emulsion for at least 24 months; and wherein the emulsion does not contain any metabolisable oil.