VanCott TC, Kaminski R, Lewis M, Mascola J, Wassef N, Alving C, Ulrich T, Richardson C, Lowell G, Burnett P, VanHamont J, Hallberg P, Lu Y, Amselem S, Burke D, McNeil J, Birx D; International Conference on AIDS.
Int Conf AIDS. 1996 Jul 7-12; 11: 13 (abstract no. We.A.391).
Henry M Jackson Foundation, Rockville, MD, USA. Fax: 301-762-4177. E-mail: tvancott@hiv.hjf.org.
Objectives: Study the immunogenicity of an oligomeric gp160 (o-gp160) protein administered parenterally to Rhesus Macaques, rabbits and mice and mucosally to mice. Assess the immunogenicity of vaccine formulations with respect to their efficiency in eliciting systemic and mucosal antibodies (IgG, IgA) capable of binding native forms of HIV-1 env and neutralizing both diverse laboratory-adapted (LA) and primary HIV-1 isolates. Methods: Rabbits were immunized intramuscularly (im) at 0,3,6 or 0,3,12 weeks with o-gp160 (70 ug) formulated in Alhydrogel or monophosphoryl lipid A (MPL). Rhesus macaques were immunized im at 0,1,6 months with o-gp160 (100 ug) formulated with Alhydrogel, MPL or polyphosphazene. Mice were immunized intranasally with o-gp160 (3, 10, 50 ug) at 0,3,6 weeks formulated in liposomes (plus or minus MPL), MPL, proteosomes or biodegradable microspheres. Serum, vaginal lavage and fecal pellets were obtained from mice after each immunization and lung and gut lavage were collected at sacrifice (week 8). Sera and lavage were screened for ogp160-specific IgG and IgA binding antibody and HIV-1 neutralizing activity. Results: Sera from immunized rabbits bound preferentially to native forms of monomeric gp120, bound to heterologous strains of gp120 and cell surface expressed HIV-1 envelope glycoprotein (IIIb, MN, RF, CDC451), neutralized diverse LA HIV-1 (IIIB, MN, RF) and had neutralizing activity against some primary isolates. Sera from immunized macaques (after two injections) also bound preferentially to native forms of gp120 and had neutralizing activity against heterologous LA HIV-1 isolates. All adjuvanted intranasally immunized mice developed strong serum IgG and IgA titers after 2 immunizations. Vaginal IgA/IgG responses were detected after 2 immunizations in mice receiving intranasal but not subcutaneous ogp160. Conclusions: Oligomeric gp160 formulated with MPL and administered intramuscularly elicits an antibody response qualitatively similar to that obtained during natural HIV-1 infection and distinct from responses obtained with other monomeric HIV-1 envelope vaccines studied to date with respect to preferential recognition of natively folded HIV-1 env and neutralizing activity against some primary HIV-1 isolates. This immunogen can also be formulated with several adjuvants to elicit serum and vaginal IgG/IgA titers in mice after 1-2 intranasal immunizations.
Publication Types:
Keywords:
- AIDS Vaccines
- Administration, Intranasal
- Animals
- Antigens, Viral
- Female
- Gene Products, env
- HIV Envelope Protein gp120
- HIV-1
- Immunization
- Mice
- Mucous Membrane
- Nasal Mucosa
- Rabbits
- Vaccination
- Vagina
- immunology
Other ID:
UI: 102219045
From Meeting Abstracts