Vaginal immunization of rats with a synthetic peptide from human immunodeficiency virus envelope glycoprotein.
Local secretory immunity in the vagina may confer a degree of protection against heterosexual transmission of human immunodeficiency virus (HIV). Since the vagina has been shown to respond to local immunization, we have undertaken intravaginal immunization of rats with a 20-mer peptide (amino acid residues 102 to 121) of the HIV-1 envelope glycoprotein (gp120). The peptide was administered in combination with an 'absorption enhancer', lysophosphatidyl glycerol (LPG), which has previously been shown to promote the absorption of intravaginally administered peptides, while exerting only mild effects on epithelial membrane integrity. Intravaginal immunization with LPG and the peptide induced serum and vaginal wash IgA and IgG antibody responses which were enhanced in comparison to those after immunization with the peptide alone. Serum antibodies induced by both subcutaneous and intravaginal immunization were able to recognize recombinant HIV-1 gp120. However, the rat antiserum displayed no neutralizing activity against the virus. These results demonstrate that LPG is an effective immunological adjuvant for intravaginally administered peptide antigens. An alternative absorption enhancer, bestatin (BES), was not effective as an immunological adjuvant when administered intravaginally and blocked the adjuvant activity of LPG when BES and LPG were used in combination.
O'Hagan
D T
DT
Department of Pharmaceutical Sciences, University of Nottingham, University Park, U.K.
Rafferty
D
D
McKeating
J A
JA
Illum
L
L
D016915:AIDS Vaccines / Q000276:immunology*; D000276:Adjuvants, Immunologic; D000818:Animals; D005260:Female; D015483:HIV Antibodies / Q000096:biosynthesis*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D007930:Leucine / Q000031:analogs & derivatives; D008246:Lysophospholipids; D010446:Peptide Fragments / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D014614:Vaccines, Synthetic / Q000276:immunology; D014621:Vagina / Q000276:immunology*
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D008246:Lysophospholipids; D010446:Peptide Fragments; D014614:Vaccines, Synthetic; C026223:lysophosphatidylglycerol; D007930:Leucine; C012211:ubenimex