Co-immunization with multimeric scaffolds and DNA rapidly induces potent autologous HIV-1 neutralizing antibodies and CD8 + T cells

Juan Pablo Jaworski, Shelly J. Krebs, Maria Trovato, Dina N. Kovarik, Zachary Brower, William F. Sutton, Garrett Waagmeester, Rossella Sartorius, Luciana D'Apice, Antonella Caivano, Nicole A. Doria-Rose, Delphine Malherbe, David C. Montefiori, Susan Barnett, Piergiuseppe de Berardinis, Nancy L. Haigwood

    Research output: Contribution to journalArticle

    24 Scopus citations

    Abstract

    To obtain proof of concept for HIV vaccines, we generated recombinant multimeric particles displaying the HIV-1 Envelope (Env) third hypervariable region (V3) as an N-terminal fusion protein on the E2 subunit of the pyruvate dehydrogenase complex of Geobacillus stearothermophilus. The E2 scaffold self-assembles into a 60-mer core that is 24 nm in diameter, with a molecular weight of 1.5 MDa, similar to a virus like particle with up to 60 copies of a heterologous protein accessible on the surface. Env(V3)-E2 multimers were tested alone and in combination with Env(gp160) DNA in mice and rabbits. Following two or more co-immunizations with Env(V3)-E2 and Env gp160 DNA, all 18 rabbits developed potent autologous neutralizing antibodies specific for V3 in six weeks. These neutralizing antibodies were sustained for 16 weeks without boosting, and comparable responses were obtained when lipopolysaccharide, a contaminant from expression in E. coli, was removed. Co-immunizations of Env(V3)-E2 and DNA expressing gp160 elicited moderate CD8-specific responses and Env-specific antibodies in mice. Co-immunization with DNA and E2 was superior to individual or sequential vaccination with these components in eliciting both neutralizing antibodies in rabbits and CD8 + T cell responses in mice. Co-immunization with DNA and multimeric E2 scaffolds appears to offer a highly effective means of eliciting rapid, specific, and sustained immune responses that may be a useful approach for other vaccine targets.

    Original languageEnglish (US)
    Article numbere31464
    JournalPloS one
    Volume7
    Issue number2
    DOIs
    StatePublished - Feb 16 2012

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)
    • Agricultural and Biological Sciences(all)
    • General

    Fingerprint Dive into the research topics of 'Co-immunization with multimeric scaffolds and DNA rapidly induces potent autologous HIV-1 neutralizing antibodies and CD8 <sup>+</sup> T cells'. Together they form a unique fingerprint.

  • Cite this

    Jaworski, J. P., Krebs, S. J., Trovato, M., Kovarik, D. N., Brower, Z., Sutton, W. F., Waagmeester, G., Sartorius, R., D'Apice, L., Caivano, A., Doria-Rose, N. A., Malherbe, D., Montefiori, D. C., Barnett, S., de Berardinis, P., & Haigwood, N. L. (2012). Co-immunization with multimeric scaffolds and DNA rapidly induces potent autologous HIV-1 neutralizing antibodies and CD8 + T cells. PloS one, 7(2), [e31464]. https://doi.org/10.1371/journal.pone.0031464