Intravaginal immunization in sheep using a bioadhesive microsphere antigen delivery system.
An enzymatically cleaved glycoprotein fragment (amino acids 28-328: 40 kDa) from influenza virus haemagglutinin (TOPS) was used to assess an intravaginal antigen delivery system, comprising lysophosphatidylcholine (LPC) and degradable starch microspheres (DSM). Three groups of three sheep received intravaginal immunization with TOPS as follows: group 2, TOPS in solution; group 3, TOPS and DSM/LPC as a powder formulation and group 4, TOPS and LPC in solution. A fourth group, group 1, received intramuscular immunization with TOPS adsorbed to aluminium hydroxide gel (Alugel). Intravaginal immunizations were repeated on two consecutive days. Two weeks later, booster doses of the same formulations were administered on two consecutive days to each group. Group 1 sheep were boosted with a single injection, 2 weeks after the single primary immunization. The serum and vaginal wash IgA and IgG antibody responses were compared among the four groups of sheep at days 15, 30 and 45 after the booster immunizations. At day 45, the serum IgG and the vaginal wash IgA antibody responses induced by TOPS and DSM/LPC (group 3), were significantly greater than the responses induced by intravaginal immunization with TOPS (group 2). However, the highest levels of antibodies in serum and vaginal wash samples were induced by intramuscular immunization with TOPS and Alugel (group 1). Intravaginal immunization with TOPS and LPC (group 4) did not result in the induction of enhanced levels of antibodies in serum or vaginal wash samples.
O'Hagan
D T
DT
Department of Pharmaceutical Sciences, University of Nottingham, University Park, UK.
Rafferty
D
D
Wharton
S
S
Illum
L
L
D000282:Administration, Intravaginal; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000097:blood; D016503:Drug Delivery Systems; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000008:administration & dosage / Q000276:immunology*; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000097:blood; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D008244:Lysophosphatidylcholines; D008863:Microspheres; D012756:Sheep; D014611:Vaccination; D014621:Vagina / Q000276:immunology*
D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008244:Lysophosphatidylcholines