Fusion protein construct and method for inducing...

Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – 25 or more amino acid residues in defined sequence

Reexamination Certificate

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C530S350000, C530S826000, C424S185100, C424S188100, C424S192100, C424S202100, C424S204100

Reexamination Certificate

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10655667

ABSTRACT:
The present invention provides a fusion protein construct (gp41HA) consisting of the ectodomain of the HIV-1IIIBenvelope glycoprotein gp41 fused to a fragment of the influenza virus HA2 hemagglutinin protein. Immunization in-vivo via an intraperitoneal prime followed by intranasal or intragastric boosts with gp41HA induces high concentrations of serum IgG antibodies and fecal IgA antibodies that reacted with gp41 in HIV-1IIIBviral lysate and are cross-reactive with gp41 in HIV-1MNlysate. Followup analyses by indirect immunofluorescence showed that both serum IgG and fecal IgA recognized human peripheral blood mononuclear cells infected with either syncytium-inducing (SI) or non-syncytium-inducing (NSI) North American HIV-1 field isolates, but not uninfected cells.

REFERENCES:
Abaza et al, “Effects of amino acid substitutions outside an antigenic site on protein binding to monoclonal antibodies of predetermined specificity obtained by peptide immunization”, Journal of Protein Chemistry, vol. 11, No. 5 (1992), pp. 433-444.
Cruse et al. Illustrated Dictionary of Immunology (Boca Raton, FL, CRC Press, Inc., 1995), p. 309. QR180.4.C78.
Paul, Fundamental Immunology, (Philadelphia & New York, Lippincott-Raven Publishers, 1993), pp. 250 and 1311-1312. QR181.F84.
Cohen et al. “Pronounced acute immunosuppression in vivo mediated by HIV Tat challenge”, Proceedings of the National Academy of Sciences of the United States of America, vol. 96, Issue 19(Sep. 14, 1999), pp. 10842-10847.
Weissenhorn et al. “Assembly of a rod-shaped chimera of a trimeric GCN4 zipper and the HIV-1 gp41 ectodomain expressed inEscherichia coli” Proceedings of the National Academy of Sciences. USA vol. 94, (Jun. 1997) pp. 6065-6069.
Harbury et al., SCIENCE * vol. 262 * Nov. 26, 1993; p. 1401-1407.

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