Recombinant HIV-1 gp120 immunogen with three different V3...

Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives

Reexamination Certificate

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C536S023400, C424S188100

Reexamination Certificate

active

07847085

ABSTRACT:
A novel immunogenic HIV-1 Env, particularly gp120, DNA construct is disclosed in which either the V1/V2 loop and the V4 loop, or all three variable loops, including V3, are replaced with a V3 sequence each of which is from a different viral isolate. Preferably, each replacement V3 loop is a consensus sequence of V3 of a different clade. Such constructs are useful as immunogens as each presents three independent V3 epitopes, so that the immunized subject generates a more broadly reactive neutralizing antibody response than with conventional gp120 or V3 DNA or polypeptide immunogens. Also disclosed are methods of using the DNA construct to immunize a mammal, preferably a human, particularly in a priming regiment in which the DNA immunogen is followed by administration of a V3 fusion protein boosting immunogen.

REFERENCES:
Liang et al., Epitope insertion into variable loops of HIV-1 gp120 as a potential means to improve immunogenicity of viral envelope protein, Vaccine, 1999, 17:2862-2872.
Gomez et al., Efficient CD8+ T cell response to the HIV-env V3 loop epitope from multiple virus isolates by a DNA prime/vaccinia virus boost (rWR and rMVA strains) immunization regime and enhancement by the cytokine IFN-γ, Virus Research, 2004, 105:11-22.
Andre et al., Increased Immune Response Elicited by DNA Vaccination with a Synthetic gp120 Sequence with Optimized Codon Usage, Journal of Virology, 1998, 72(2):1497-1503.
Arnold, GF et al., “Broad Neutralization of Human Immunodeficiency Virus Type 1 (HIV-1) Elicited from Human Rhinoviruses That Display the HIV-1 gp41 ELDKWA Epitope,” J. Virol. 83:5087-5100 (2009) = supplemental Table 1.

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