Sequential immunization with a subtype B HIV-1 envelope quasispecies partially mimics the in Vivo development of neutralizing antibodies

Delphine C. Malherbe, Nicole A. Doria-Rose, Lynda Misher, Travis Beckett, Wendy Blay Puryear, Jason T. Schuman, Zane Kraft, Jean O'Malley, Motomi Mori, Indresh Srivastava, Susan Barnett, Leonidas Stamatatos, Nancy L. Haigwood

    Research output: Contribution to journalArticlepeer-review

    72 Scopus citations

    Abstract

    A major goal of human immunodeficiency virus type 1 (HIV-1) vaccine efforts is the design of Envelope (Env)-based immunogens effective at eliciting heterologous or broad neutralizing antibodies (NAbs). We hypothesized that programming the B-cell response could be achieved by sequentially exposing the host to a collection of env variants representing the viral quasispecies members isolated from an individual that developed broad NAbs over time. This ordered vaccine approach (sequential) was compared to exposure to a cocktail of env clones (mixture) and to a single env variant (clonal). The three strategies induced comparable levels of the autologous and heterologous neutralization of tier 1 pseudoviruses. Sequential and mixture exposure to quasispecies led to epitope targeting similar to that observed in the simian-human immunodeficiency virus (SHIV)-infected animal from which the env variants were cloned, while clonal and sequential exposure led to greater antibody maturation than the mixture. Therefore, the sequential vaccine approach best replicated the features of the NAb response observed in that animal. This study is the first to explore the use of a collection of HIV-1 env quasispecies variants as immunogens and to present evidence that it is possible to educate the B-cell response by sequential exposure to native HIV-1 quasispecies env variants derived from an individual with a broadened NAb response.

    Original languageEnglish (US)
    Pages (from-to)5262-5274
    Number of pages13
    JournalJournal of virology
    Volume85
    Issue number11
    DOIs
    StatePublished - Jun 2011

    ASJC Scopus subject areas

    • Microbiology
    • Immunology
    • Insect Science
    • Virology

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