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

PloS One
Juan Pablo JaworskiNancy L Haigwood

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 antibodi...Continue Reading

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Citations

Jan 1, 2014·Vaccines·Barbara K FelberGeorge N Pavlakis
Jun 8, 2014·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Diego A Vargas-InchausteguiMarjorie Robert-Guroff
Aug 9, 2013·Current Opinion in HIV and AIDS·Ivelin S GeorgievPeter D Kwong
Jul 4, 2012·International Journal of Molecular Sciences·Marco SchiavoneGiuseppe Scala
Feb 12, 2012·World Journal of Virology·Maria TrovatoPiergiuseppe De Berardinis
Jul 26, 2018·Genes·Dennis DiazAnwar Sunna
Dec 19, 2017·Expert Review of Vaccines·Michael Barry
Nov 10, 2020·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Nina ButkovichSzu-Wen Wang
May 20, 2021·Acta Biomaterialia·Conor L O'NeillJai S Rudra

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Methods Mentioned

BETA
antigen display
gel filtration
size exclusion chromatography
ELISA
flow cytometry
PCR
Assay
Infrared Imaging
FCS
FACS

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