AIDS RESEARCH AND HUMAN RETROVIRUSES Volume 8, Number 8, 1992 Mary Ann Liebert, Inc., Publishers

Immunization of Primates with Native, Recombinant HIV-SF2 gpl20 Generates Broadly Effective Neutralizing Antibodies Directed to Conformational Epitopes

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K.S. STEIMER and N.L. HAIGWOOD

gpl20 WE(rgpl20SF2)genetically produced fully glycosylated, engineered HAVE shown that

recombinant HIV-SF2

as a

native

mammalian cells, binds polypeptide in neutralizing antibodies from human HIV antibody-positive sera directed to linear

as

well

as

conformational determinants in

gpl20. Antibodies directed to linear determinants in rgpl20SF2, including those directed to the well-characterized principal neutralizing determinant (PND), effectively neutralized only isolates that were closely related sequentially to H1V-SF2. In contrast, antibodies directed to conformation-dependent epitopes in rgpl20SF2 neutralized a broad spectrum of virus isolates. These gpl20-specific conformation-dependent neutralizing antibodies, but not antibodies directed to linear determinants in rgpl20SF2, blocked the binding of gpl20 to CD4. In parallel with our studies of the neutralizing activity of human HIV-positive sera, we have carried out immunogenicity studies with rgpl20SF2 in primates. With several adjuvant formulations, a broadening of the neutralizing response to isolates HIV-MN and HIV-BRU was observed following three to five immunizations. A further broadening to African and Caribbean isolates

Chiron

occurred upon administration of additional doses of antigen. Broadening to isolates with homology in the central six amino acids (GPGRAF) of the PND was the result of very effective presentation of this region by rgpl20SF2. In high titer baboon sera, V3 peptides blocked some, but not all, neutralizing activity against non-African isolates. Consistent with our studies of human gpl20-specific antibodies, broadening of the response of rgpl20SF2-immunized primates to isolates unrelated to the PND was shown to be the result of induction of antibodies directed to conformation-dependent epitopes in gpl20. We are currently testing linear- and conformation-dependent neutralizing antibodies purified from rgpl20SF2-immunized baboons for their ability to block the binding of gp 120 to CD4.

Corporation. 4560 Horton Street, Emeryville, CA. 1391

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to:

K.S. Steimer

Chiron Corporation 4560 Horton Street Emeryville, CA

Immunization of primates with native, recombinant HIV-SF2 gp120 generates broadly effective neutralizing antibodies directed to conformational epitopes.

AIDS RESEARCH AND HUMAN RETROVIRUSES Volume 8, Number 8, 1992 Mary Ann Liebert, Inc., Publishers Immunization of Primates with Native, Recombinant HI...
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