Abstract

Twenty samples of commercial vaccines intended for administration to humans were assayed for the presence of bacterial endotoxins by using the Limulus amebocyte lysate test. Sixteen of the vaccines contained more than 0.1 ng of endotoxin per ml (which corresponds to 103 bacterial cell wall equivalents per ml in the undiluted vaccines). These results suggest that at some stage of preparation, the vaccines have contained varying amounts of gram-negative bacteria and may indicate the presence of other bacterial products as well. It might be useful to list the level of endotoxins, phage, and other contaminants on each vaccine lot to facilitate studies on any side effects of these contaminants. Selection of vaccine lots with the least endotoxin might reduce some of the adverse effects of vaccinations.

Selected References

• Barry DW, Mayner RE, Hochstein HD, Dunlap RC, Rastogi SC, Hannah JE, Blackburn RJ, Sullivan JL, Gerety RJ. Comparative trial of influenza vaccines. II. Adverse reactions in children and adults. Am J Epidemiol. 1976 Jul;104(1):47–59. [PubMed] [Google Scholar]
• Chu FC, Johnson JB, Orr HC, Probst PG, Petricciani JC. Bacterial virus contamination of fetal bovine sera. In Vitro. 1973 Jul-Aug;9(1):31–34. [PubMed] [Google Scholar]
• Cooper JF, Levin J, Wagner HN., Jr Quantitative comparison of in vitro and in vivo methods for the detection of endotoxin. J Lab Clin Med. 1971 Jul;78(1):138–148. [PubMed] [Google Scholar]
• Daoust DR, Orlowski SJ, McMahon G, Weber CK, Shaw WC, Fisher TC, Bennett CR, Gray A. Limulus amebocyte lysate test as a method for detection of endotoxins and endotoxin-like materials. Bull Parenter Drug Assoc. 1976 Jan-Feb;30(1):13–20. [PubMed] [Google Scholar]
• Elin RJ, Sandberg AL, Rosentreich DL. Comparison of the pyrogenicity, Limulus activity mitogenicity and complement reactivity of several bacterial endotoxins and related compounds. J Immunol. 1976 Oct;117(4):1238–1242. [PubMed] [Google Scholar]
• Elin RJ, Wolff SM. Nonspecificity of the limulus amebocyte lysate test: positive reactions with polynucleotides and proteins. J Infect Dis. 1973 Sep;128(3):349–352. [PubMed] [Google Scholar]
• Geier MR, Attallah AF, Merril CR. Characterization of Escherichia coli bacterial viruses in commercial sera,. In Vitro. 1975 Jan-Feb;11(1):55–58. [PubMed] [Google Scholar]
• HJORT PF, RAPAPORT SI. THE SHWARTZMAN REACTION: PATHOGENETIC MECHANISMS AND CLINICAL MANIFESTATIONS. Annu Rev Med. 1965;16:135–168. [PubMed] [Google Scholar]
• Jorgensen JH, Carvajal HF, Chipps BE, Smith RF. Rapid detection of gram-negative bacteriuria by use of the Limulus endotoxin assay. Appl Microbiol. 1973 Jul;26(1):38–42. [PMC free article] [PubMed] [Google Scholar]
• Jorgensen JH, Lee JC, Pahren HR. Rapid detection of bacterial endotoxins in drinking water and renovated wastewater. Appl Environ Microbiol. 1976 Sep;32(3):347–351. [PMC free article] [PubMed] [Google Scholar]
• Kreeftenberg JG, Loggen HG, van Ramshorst JD, Beuvery EC. The limulus amebocyte lysate test micromethod and application in the control of sera and vaccines. Dev Biol Stand. 1977;34:15–20. [PubMed] [Google Scholar]
• Kuronen T, Peltola H, Nors T, Haque N, Mäkelä PH. Adverse reactions and endotoxin content of polysaccharide vaccines. Dev Biol Stand. 1977;34:117–125. [PubMed] [Google Scholar]
• Levin J, Bang FB. Clottable protein in Limulus; its localization and kinetics of its coagulation by endotoxin. Thromb Diath Haemorrh. 1968 Mar 31;19(1):186–197. [PubMed] [Google Scholar]
• Levin J, Poore TE, Zauber NP, Oser RS. Detection of endotoxin in the blood of patients with sepsis due to gran-negative bacteria. N Engl J Med. 1970 Dec 10;283(24):1313–1316. [PubMed] [Google Scholar]
• Merril CR, Friedman TB, Attallah AF, Geier MR, Krell K, Yarkin R. Isolation of bacteriophages from commercial sera. In Vitro. 1972 Sep-Oct;8(2):91–93. [PubMed] [Google Scholar]
• Moody EE, Trousdale MD, Jorgensen JH, Shelokov A. Bacteriophages and endotoxin in licensed live-virus vaccines. J Infect Dis. 1975 May;131(5):588–591. [PubMed] [Google Scholar]
• Murata H, Kobayashi M, Iio M, Yamada H, Chilba K. Sensitivity of the Limulus test and inhibitory factors in the radiopharmaceuticals. J Nucl Med. 1976 Dec;17(12):1088–1092. [PubMed] [Google Scholar]
• Nandan R, Brown DR. An improved in vitro pyrogen test: to detect picograms of endotoxin contamination in intravenous fluids using limulus amoebocyte lysate. J Lab Clin Med. 1977 Apr;89(4):910–918. [PubMed] [Google Scholar]
• Orr HC, Sibinovic KH, Probst PG, Hochstein HD, Littlejohn DC. Bacteriological activity in unfiltered calf sera collected for tissue culture use. In Vitro. 1975 Jul-Aug;11(4):230–233. [PubMed] [Google Scholar]
• Petricciani JC, Chu FC, Johnson JB, Meyer HM., Jr Bacteriophages in live virus vaccines. Proc Soc Exp Biol Med. 1973 Dec;144(3):789–792. [PubMed] [Google Scholar]
• Reichelderfer PS, Manischewitz JF, Wells MA, Hochstein HD, Ennis FA. Reduction of endotoxin levels in influenza virus vaccines by barium sulfate adsorption-elution. Appl Microbiol. 1975 Aug;30(2):333–334. [PMC free article] [PubMed] [Google Scholar]
• Reinhold RB, Fine J. A technique for quantitative measurement of endotoxin in human plasma. Proc Soc Exp Biol Med. 1971 May;137(1):334–340. [PubMed] [Google Scholar]
• Rojas-Corona RR, Skarnes R, Tamakuma S, Fine J. The Limulus coagulation test for endotoxin. A comparison with other assay methods. Proc Soc Exp Biol Med. 1969 Nov;132(2):599–601. [PubMed] [Google Scholar]
• Siegel SE, Nachum R, Leimbrock S, Karon M. Detection of bacterial endotoxin in antitumor agents. Cancer Treat Rep. 1976 Jan;60(1):9–15. [PubMed] [Google Scholar]
• Yin ET. Endotoxin, thrombin, and the Limulus amebocyte lysate test. J Lab Clin Med. 1975 Sep;86(3):430–434. [PubMed] [Google Scholar]
• Tomasulo PA, Levin J, Murphy PA, Winkelstein JA. Biological activities of tritiated endotoxins: correlation of the Limulus lysate assay with rabbit pyrogen and complement-activation assays for endotoxin. J Lab Clin Med. 1977 Feb;89(2):308–315. [PubMed] [Google Scholar]
• van Noordwijk J, de Jong Y. Comparison of the Limulus test for endotoxin with the rabbit test for pyrogens of European Pharmacopoeia. J Biol Stand. 1976 Apr;4(2):131–139. [PubMed] [Google Scholar]
• Wachtel RE, Tsuji K. Comparison of limulus amebocyte lysates and correlation with the United States Pharmacopeial pyrogen test. Appl Environ Microbiol. 1977 Jun;33(6):1265–1269. [PMC free article] [PubMed] [Google Scholar]
• Wildfeuer A, Heymer B, Schleifer KH, Haferkamp O. Investigations on the specificity of the Limulus test for the detection of endotoxin. Appl Microbiol. 1974 Nov;28(5):867–871. [PMC free article] [PubMed] [Google Scholar]
• ZWEIFACH BW, JANOFF A. BACTERIAL ENDOTOXEMIA. Annu Rev Med. 1965;16:201–220. [PubMed] [Google Scholar]