title: Induction of antibodies against epitopes inaccessible on the HIV type 1 envelope oligomer by immunization with recombinant monomeric glycoprotein 120.
abstract: An N-glycan (N306) at the base of the V3 loop of HIV-BRU gp120 is shielding a linear neutralization epitope at the tip of the V3 loop on oligomeric Env. In contrast, this epitope is readily antigenic on monomeric gp120. Immunization with recombinant monomeric HIV-BRU gp120 may thus be expected to elicit antibodies preferentially neutralizing mutant variants of HIV-BRU lacking the N306 glycan. Therefore, two guinea pigs were immunized with monomeric wild-type HIV-BRU gp120 possessing the N306 glycan and immune sera were tested for neutralization against target viruses HIV-BRU, -A308, and -A308T321. HIV-A308 and HIV-A308T321 lack the N306 glycan; HIV-A308T321 contains an additional mutation at the tip of V3 rendering it resistant to MAb binding at this epitope. Both immune sera preferentially neutralized the two mutant virus variants lacking the N306 glycan, with a 10- to 20-fold increase in neutralization titer compared with the wild-type HIV-BRU. Thus, immunization with monomeric HIV-BRU gp120 elicited antibodies preferentially neutralizing HIV variants lacking the N306 glycan. In addition to antibodies directed against the tip of V3, other antibodies directed against epitopes shielded by the N306 glycan on the envelope oligomer were elicited by the immunization, as demonstrated by the ability of the immune sera to neutralize HIV-A308T321. One such epitope was overlapping the NEA-9284 epitope located at the amino-terminal flank of the V3 loop. Our results demonstrate that monomeric gp120 contains immunogenic structures inaccessible on the envelope oligomer. The limited ability of recombinant gp120 vaccines to induce neutralizing antibodies against primary isolates may thus not exclusively reflect genetic variation.
authors.affiliation: Laboratory of Infectious Diseases, Department 144, Hvidovre Hospital, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Schønning
authors.forename: A
authors.initials: A
authors.lastname: Bolmstedt
authors.forename: J
authors.initials: J
authors.lastname: Novotny
authors.forename: O S
authors.initials: OS
authors.lastname: Lund
authors.forename: S
authors.initials: S
authors.lastname: Olofsson
authors.forename: J E
authors.initials: JE
authors.lastname: Hansen
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D006168:Guinea Pigs; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007114:Immunization; D009842:Oligopeptides / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D018985:Epitopes, B-Lymphocyte; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D009842:Oligopeptides; D010446:Peptide Fragments; D014614:Vaccines, Synthetic