A fusion protein containing the adenovirus type 2 fiber trimerizing and knob domains linked to HIV-1 gp120 exhibits increased nasal immunogenicity in rabbits (VAC8P.1046)

We previously reported that the inclusion of the trimerizing and knob domains from adenovirus type 2 fiber (Ad2F) in protein immunogens enhanced their mucosal binding and immunogenicity when delivered nasally. This study was performed to determine if Ad2F would enhance the nasal immunogenicity of HIV-1 gp120 from the Clade C Env C.1086. A fusion protein with Ad2F at the C-terminus of HIV-1 gp120 was used as gp120-Ad2F. NZW rabbits were nasally immunized with 100, 200 or 300 µg of gp120 or equimolar doses of gp120-Ad2F fusion proteins adjuvanted with the cationic mast cell activating peptide mastoparan 7 on days 0 and boosted on days 28 - 34. Intramuscular immunization with 100 µg gp120 adjuvanted with an MF59-like adjuvant served as the positive control. Serum anti-HIV-1 gp120 IgG titers were measured 2 weeks after the final boost. While only the 200 and 300 µg doses of gp120 delivered intranasally induced serum anti-gp120 IgG similar to those induced by IM immunization, all doses of gp120-Ad2F fusion proteins induced serum anti-gp120 IgG titers similar to those induced by IM immunization. While the 100 µg dose of gp120 delivered nasally induced serum anti-gp120 IgG titers significantly lower than that induced by 300 µg of gp120 delivered nasally, all doses of gp120-Ad2F induced similar anti-gp120 IgG titers. Our results demonstrate that the addition of Ad2F to HIV-1 gp120 enhances its nasal immunogenicity, lessening the amount of gp120 required for vaccination.