Search

Your search keyword '"N. A. Doria-Rose"' showing total 2 results
Start Over Author "N. A. Doria-Rose" Search Limiters Full Text
2 results on '"N. A. Doria-Rose"'

1. Multigene DNA Priming-Boosting Vaccines Protect Macaques from Acute CD4+-T-Cell Depletion after Simian-Human Immunodeficiency Virus SHIV89.6P Mucosal Challenge

Author

LaRene Kuller, Nancy L. Haigwood, Shiu Lok Hu, Thera M. Mulvania, P. D. Greenberg, N. A. Doria-Rose, C. C. Pierce, Donovan J. Anderson, Patricia Polacino, C. Ohlen, and M. T. Hensel

Subjects
CD4-Positive T-Lymphocytes, Cellular immunity, viruses, Immunology, Immunization, Secondary, Simian Acquired Immunodeficiency Syndrome, Priming (immunology), HIV Infections, Vaccinia virus, Biology, Antibodies, Viral, medicine.disease_cause, complex mixtures, Microbiology, Virus, HIV Envelope Protein gp160, Gene gun, law.invention, Viral Proteins, chemistry.chemical_compound, law, Virology, Vaccines and Antiviral Agents, Vaccines, DNA, medicine, Animals, Humans, AIDS Vaccines, Immunity, Cellular, Boosting (doping), Cd4 t cell, Errata, SAIDS Vaccines, Simian human immunodeficiency virus, Biolistics, Simian immunodeficiency virus, chemistry, Insect Science, HIV-1, Recombinant DNA, Immunization, Simian Immunodeficiency Virus, Macaca nemestrina, Vaccinia, DNA
Abstract

We evaluated four priming-boosting vaccine regimens for the highly pathogenic simian human immunodeficiency virus SHIV89.6P inMacaca nemestrina. Each regimen included gene gun delivery of a DNA vaccine expressing all SHIV89.6 genes plus Env gp160 of SHIV89.6P. Additional components were two recombinant vaccinia viruses, expressing SHIV89.6 Gag-Pol or Env gp160, and inactivated SHIV89.6 virus. We compared (i) DNA priming/DNA boosting, (ii) DNA priming/inactivated virus boosting, (iii) DNA priming/vaccinia virus boosting, and (iv) vaccinia virus priming/DNA boosting versus sham vaccines in groups of 6 macaques. Prechallenge antibody responses to Env and Gag were strongest in the groups that received vaccinia virus priming or boosting. Cellular immunity to SHIV89.6 peptides was measured by enzyme-linked immunospot assay; strong responses to Gag and Env were found in 9 of 12 vaccinia virus vaccinees and 1 of 6 DNA-primed/inactivated-virus-boosted animals. Vaccinated macaques were challenged intrarectally with 50 50% animal infectious doses of SHIV89.6P 3 weeks after the last immunization. All animals became infected. Five of six DNA-vaccinated and 5 of 6 DNA-primed/particle-boosted animals, as well as all 6 controls, experienced severe CD4+-T-cell loss in the first 3 weeks after infection. In contrast, DNA priming/vaccinia virus boosting and vaccinia virus priming/DNA boosting vaccines both protected animals from disease: 11 of 12 macaques had no loss of CD4+T cells or moderate declines. Virus loads in plasma at the set point were significantly lower in vaccinia virus-primed/DNA-boosted animals versus controls (P= 0.03). We conclude that multigene vaccines delivered by a combination of vaccinia virus and gene gun-delivered DNA were effective against SHIV89.6P viral challenge inM. nemestrina.

Published
2003

2. Rational design of a trispecific antibody targeting the HIV-1 Env with elevated anti-viral activity.

Author

Steinhardt JJ, Guenaga J, Turner HL, McKee K, Louder MK, O'Dell S, Chiang CI, Lei L, Galkin A, Andrianov AK, A Doria-Rose N, Bailer RT, Ward AB, Mascola JR, and Li Y

Subjects
Antibodies, Neutralizing chemistry, Antibodies, Neutralizing immunology, Antibodies, Neutralizing pharmacology, Antibodies, Neutralizing therapeutic use, Antiviral Agents chemistry, Antiviral Agents immunology, Antiviral Agents therapeutic use, Drug Combinations, Epitopes genetics, Epitopes immunology, HIV Antibodies chemistry, HIV Antibodies immunology, HIV Antibodies therapeutic use, HIV-1 genetics, HIV-1 immunology, Humans, Microscopy, Electron, Mutation, Protein Subunits immunology, Single-Chain Antibodies chemistry, Single-Chain Antibodies immunology, Single-Chain Antibodies pharmacology, Single-Chain Antibodies therapeutic use, env Gene Products, Human Immunodeficiency Virus genetics, env Gene Products, Human Immunodeficiency Virus immunology, Antiviral Agents pharmacology, Drug Design, HIV Antibodies pharmacology, HIV Infections drug therapy, HIV-1 drug effects, env Gene Products, Human Immunodeficiency Virus antagonists & inhibitors
Abstract

HIV-1 broadly neutralizing antibodies (bNAbs) are being explored as passively administered therapeutic and preventative agents. However, the extensively diversified HIV-1 envelope glycoproteins (Env) rapidly acquire mutations to evade individual bNAbs in monotherapy regimens. The use of a "single" agent to simultaneously target distinct Env epitopes is desirable to overcome viral diversity. Here, we report the use of tandem single-chain variable fragment (ScFv) domains of two bNAbs, specific for the CD4-binding site and V3 glycan patch, to form anti-HIV-1 bispecific ScFvs (Bi-ScFvs). The optimal Bi-ScFv crosslinks adjacent protomers within one HIV-1 Env spike and has greater neutralization breadth than its parental bNAbs. Furthermore, the combination of this Bi-ScFv with a third bNAb recognizing the Env membrane proximal external region (MPER) results in a trispecific bNAb, which has nearly pan-isolate neutralization breadth and high potency. Thus, multispecific antibodies combining functional moieties of bNAbs could achieve outstanding neutralization capacity with augmented avidity.

Published
2018
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results