NDLI: Co-Immunization with Multimeric Scaffolds and DNA Rapidly Induces Potent Autologous HIV-1 Neutralizing Antibodies and CD8+ T Cells

Content Provider	PubMed Central
Author	Jaworski, Juan Pablo Krebs, Shelly J. Trovato, Maria Kovarik, Dina N. Brower, Zachary Sutton, William F. Garrett, Waagmeester Sartorius, Rossella D'apice, Luciana Caivano, Antonella Doria-rose, Nicole A. Malherbe, Delphine Montefiori, David C. Barnett, Susan De Berardinis, Piergiuseppe Haigwood, Nancy L.
Editor	Nixon, Douglas F.
Copyright Year	2012
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.
Related Links	http://dx.doi.org/10.1371/journal.pone.0031464
Starting Page	31464
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	2
Volume Number	7
Language	English
Publisher	Public Library of Science
Publisher Date	2012-02-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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Correction: Multimeric Scaffolds Displaying the HIV-1 Envelope MPER Induce MPER-Specific Antibodies and Cross-Neutralizing Antibodies when Co-Immunized with gp160 DNA

Multimeric Scaffolds Displaying the HIV-1 Envelope MPER Induce MPER-Specific Antibodies and Cross-Neutralizing Antibodies when Co-Immunized with gp160 DNA

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Co-Immunization with Multimeric Scaffolds and DNA Rapidly Induces Potent Autologous HIV-1 Neutralizing Antibodies and CD8+ T Cells

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