Safety and immunogenicity, after nasal application of HIV-1 DNA gagp37 plasmid vaccine in young mice.
BACKGROUND
There is a need for safe and potent adjuvants capable of delivering vaccine candidates over the mucosal barrier, with good capacity to stimulate both mucosal and systemic cell-mediated and humoral immunity. An adjuvant aimed for intranasal delivery should preferably deliver the antigen and minimize the transfer into the close proximity of the central nervous system, thus avoiding damage on the olfactory tissues. Advantages with a mucosal delivery route would be to provide mucosal and systemic immunity, requiring lower vaccine doses then when given parentally. The aim of this study was to study if the N3 adjuvant intranasally administered with HIV DNA plasmids would be transferred into the olfactory tissues and cause local inflammation and tissue damage.


RESULTS
The N3 adjuvant alone and when combined with HIV-1 DNA gag plasmid and delivered intranasally did not cause detectable damage to the nasal epithelium or the olfactory epithelium or bulb over a period of 3 days after delivery. The intranasal administration of HIV-1 gagp37 DNA induced both a humoral and a cell-mediated immunity against the gag antigen. Significantly higher HIV-1-specific humoral, but not cell-mediated immune responses were seen in DNA/N3-immunized mice in comparison with HIV-1 DNA/saline-immunized animals.


CONCLUSIONS
A safe and convenient intranasal mode of HIV-1 DNA plasmid and adjuvant delivery was shown not to interfere with the tissues in close proximity to the central nervous system. The N3 adjuvant combined with HIV-1 plasmids enhances the HIV-1-specific immunogenicity and merits to be clinically tested.
Hinkula
Jorma
J
Department of Molecular Virology, Linkoping University, Sweden. Jorma.Hinkula@imk.liu.se
Hagbom
Marie
M
Wahren
Britta
B
Schroder
Ulf
U
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000588:Amines / Q000008:administration & dosage; D000818:Animals; D005260:Female; D005989:Glycerides / Q000008:administration & dosage; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009297:Nasal Mucosa / Q000473:pathology; D009830:Olfactory Bulb / Q000473:pathology; D010957:Plasmids / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000588:Amines; D005989:Glycerides; D019444:Vaccines, DNA; D054301:gag Gene Products, Human Immunodeficiency Virus; C005953:monoolein; C008703:oleylamine