Immunisation against plague by transcutaneous and intradermal application of subunit antigens.
We have investigated immunological responses in BALB/c mice following transcutaneous (TC) delivery of fraction 1 (F1) and V subunits from Yersinia pestis in conjunction with an enterotoxin-derived adjuvant (cholera toxin, CT). It was found that two or more TC applications of F1 and V subunits (admixed with cholera toxin) served to elicit significant levels of anti-F1 and V antibodies in the serum of immunised mice. IL-6 secretion from cultured splenocytes derived from immunised mice indicated that a single TC application of F1 and V subunits (admixed with cholera toxin) conferred a cell-mediated response. As compared with intranasal or direct intradermal injection of F1 and V, the numbers of F1/V-specific antibody-forming cells in the spleens of animals immunised by TC application of F1 and V (admixed with CT) was relatively low. It was noted that TC application of F1 and V admixed with CT was very effective for priming responses that were boosted by intranasal or intradermal routes. Similarly, it was found that TC application of F1 and V admixed with CT could be used to efficiently boost pre-existing responses engendered by intradermal injection or intranasal instillation of F1 and V. In order to assess if TC application of F1 and V admixed with CT could protect experimental animals from plague, immunised mice were injected with a virulent strain of Y. pestis. It was found that two TC applications of F1 and V admixed with CT conferred only limited protection against 10(2) MLDs. However, three TC applications of F1 and V admixed with CT conferred solid protection against 10(2) MLDs. Hence we have shown, for the first time, that TC application of F1 and V admixed with CT can protect animals against challenge with a virulent strain of plague causing bacteria. These data suggest that transcutaneous immunisation may be a simple and non-invasive method for immunising individuals against plague.
Biomedical Sciences, Dstl, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK. jeeyles@dstl.gov.uk
J E
JE
Eyles
S J
SJ
Elvin
A
A
Westwood
C S
CS
Lebutt
H O
HO
Alpar
S
S
Somavarapu
E D
ED
Williamson
D000276:Adjuvants, Immunologic; D000279:Administration, Cutaneous; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis / Q000096:biosynthesis; D000918:Antibody Specificity; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000627:therapeutic use*; D002469:Cell Separation; D002772:Cholera Toxin / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007114:Immunization / Q000379:methods; D007271:Injections, Intradermal; D007371:Interferon-gamma / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010930:Plague / Q000276:immunology* / Q000517:prevention & control*; D010931:Plague Vaccine / Q000008:administration & dosage / Q000627:therapeutic use*; D013154:Spleen / Q000166:cytology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000627:therapeutic use
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D015848:Interleukin-5; D015850:Interleukin-6; D010931:Plague Vaccine; D014614:Vaccines, Synthetic; D007371:Interferon-gamma; D002772:Cholera Toxin