title: Efforts to broaden HIV-1-specific immunity by boosting with heterologous peptides or envelope protein and the influence of prior exposure to virus.
abstract: In two previous studies, we have demonstrated the successful protection of human immunodeficiency virus type 1 (HIV-1)-vaccinated rhesus macaques from challenge with SHIV(SF13) with envelop immunogens derived from the closely related HIV-1(SF2) strain. Here we report on two follow-up studies in which we aimed to broaden immunity in order to elicit protection from a more diverse heterologous challenge with SHIV(SF33). In the first study, animals were boosted once with HIV-1(SF33) V2 and V3 peptides that were cross-linked to influenza immune-stimulating complexes (ISCOMs). In the second study, monkeys were boosted twice at 12-week intervals, using a heterologous recombinant gp120 derived from HIV-1(SF33) that was either incorporated into ISCOMs or mixed with the MF59 adjuvant. In both studies, the animals were challenged with 50 monkey infectious doses of SHIV(SF33) 4 weeks after the final boost. All controls became readily infected with the heterologous challenge virus SHIV(SF33). Neither boosting with heterologous SF33 peptides or gp120 afforded protection from infection to SF2-vaccinated animals that had previously resisted SHIV(SF13) challenge. These results demonstrate the importance of developing vaccine strategies that are capable of generating broad immune responses early in the immunization protocol. Furthermore, these findings may illustrate the potential pitfalls of early antigenic sin.
authors.affiliation: Biomedical Primate Research Centre, Department of Virology, Rijswijk, The Netherlands.
authors.forename: E J
authors.initials: EJ
authors.lastname: Verschoor
authors.forename: D
authors.initials: D
authors.lastname: Davis
authors.forename: M
authors.initials: M
authors.lastname: van Gils
authors.forename: G
authors.initials: G
authors.lastname: Koopman
authors.forename: P
authors.initials: P
authors.lastname: Mooij
authors.forename: H
authors.initials: H
authors.lastname: Oostermeijer
authors.forename: P T
authors.initials: PT
authors.lastname: Haaft
authors.forename: B
authors.initials: B
authors.lastname: Verstrepen
authors.forename: B
authors.initials: B
authors.lastname: Rosenwirth
authors.forename: B
authors.initials: B
authors.lastname: Morein
authors.forename: S W
authors.initials: SW
authors.lastname: Barnett
authors.forename: J L
authors.initials: JL
authors.lastname: Heeney
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D000939:Epitopes / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D007114:Immunization / Q000662:veterinary; D008253:Macaca mulatta; D009975:Orthomyxoviridae / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D014613:Vaccines, Attenuated / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology*; D019562:Viral Load
chemical_list: D016915:AIDS Vaccines; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D010446:Peptide Fragments; D014613:Vaccines, Attenuated; D014759:Viral Envelope Proteins