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DNA and protein co-immunization improves the magnitude and longevity of humoral immune responses in macaques

Jalah, Rashmi ; Kulkarni, Viraj ; Patel, Vainav ; Rosati, Margherita ; Alicea, Candido ; Bear, Jenifer ; Yu, Lei ; Guan, Yongjun ; Shen, Xiaoying ; Tomaras, Georgia D ; LaBranche, Celia ; Montefiori, David C ; Prattipati, Rajasekhar ; Pinter, Abraham ; Bess, Jr, Julian ; Lifson, Jeffrey D ; Reed, Steven G ; Sardesai, Niranjan Y ; Venzon, David J ; Valentin, Antonio ; Pavlakis, George N ; Felber, Barbara K Ansari, Aftab A.

PloS one, 2014-03, Vol.9 (3), p.e91550-e91550 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
DNA and protein co-immunization improves the magnitude and longevity of humoral immune responses in macaques
Autor: Jalah, Rashmi ; Kulkarni, Viraj ; Patel, Vainav ; Rosati, Margherita ; Alicea, Candido ; Bear, Jenifer ; Yu, Lei ; Guan, Yongjun ; Shen, Xiaoying ; Tomaras, Georgia D ; LaBranche, Celia ; Montefiori, David C ; Prattipati, Rajasekhar ; Pinter, Abraham ; Bess, Jr, Julian ; Lifson, Jeffrey D ; Reed, Steven G ; Sardesai, Niranjan Y ; Venzon, David J ; Valentin, Antonio ; Pavlakis, George N ; Felber, Barbara K
Ansari, Aftab A.
Assuntos: Acquired immune deficiency syndrome ; Adjuvants, Immunologic ; AIDS ; AIDS vaccines ; Animals ; Antibodies ; Antibodies, Neutralizing - immunology ; Antibodies, Viral - immunology ; Biology ; Deoxyribonucleic acid ; DNA ; DNA vaccines ; DNA, Viral - genetics ; Drug delivery systems ; Electroporation ; Female ; Gene Products, env - immunology ; HIV ; Homology ; Human immunodeficiency virus ; Immune response ; Immune response (humoral) ; Immunity, Cellular ; Immunity, Humoral ; Immunization ; Immunoglobulin G ; Immunoglobulin G - immunology ; Lactoferrin ; Lactoferrins ; Longevity ; Macaca mulatta ; Male ; Medical research ; Mucosal immunity ; Muscles ; Rectum ; SAIDS Vaccines - immunology ; Saliva ; Secretions ; Simian Immunodeficiency Virus ; Vaccination ; Vaccines ; Vaccines, DNA - immunology
É parte de: PloS one, 2014-03, Vol.9 (3), p.e91550-e91550
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Conceived and designed the experiments: AV GNP BKF. Performed the experiments: RJ VK VP MR CA JB LY YG XS GDT CL DCM. Analyzed the data: RJ MR YG XS GDT CL DCM DJV AV GNP BKF. Contributed reagents/materials/analysis tools: RP AP JBJr JDL SGR NYS GNP BKF. Wrote the paper: AV GNP BKF.
Competing Interests: I have read the journal's policy and have the following conflicts, GNP and BKF are inventors on US Government-owned patents and patent applications related to DNA vaccines and gene expression optimization that have been licensed to several companies. There are no further patents, products in development or marketed products to declare. NYS is a full time employee of Inovio Pharmaceuticals and as such receive compensation in the form of salary and stock options. SR is a founder and shareholder in Immune Design Corp. which has certain rights to the adjuvant used in this study under license agreement with IDRI. This does not alter our adherence to all PLoS Ones policies on sharing data and materials.
Descrição: We tested the concept of combining DNA with protein to improve anti-HIV Env systemic and mucosal humoral immune responses. Rhesus macaques were vaccinated with DNA, DNA&protein co-immunization or DNA prime followed by protein boost, and the magnitude and mucosal dissemination of the antibody responses were monitored in both plasma and mucosal secretions. We achieved induction of robust humoral responses by optimized DNA vaccination delivered by in vivo electroporation. These responses were greatly increased upon administration of a protein boost. Importantly, a co-immunization regimen of DNA&protein injected in the same muscle at the same time induced the highest systemic binding and neutralizing antibodies to homologous or heterologous Env as well as the highest Env-specific IgG in saliva. Inclusion of protein in the vaccine resulted in more immunized animals with Env-specific IgG in rectal fluids. Inclusion of DNA in the vaccine significantly increased the longevity of systemic humoral immune responses, whereas protein immunization, either as the only vaccine component or as boost after DNA prime, was followed by a great decline of humoral immune responses overtime. We conclude that DNA&protein co-delivery in a simple vaccine regimen combines the strength of each vaccine component, resulting in improved magnitude, extended longevity and increased mucosal dissemination of the induced antibodies in immunized rhesus macaques.
Editor: United States: Public Library of Science
Idioma: Inglês

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DNA and protein co-immunization improves the magnitude and longevity of humoral immune responses in macaques

United States: Public Library of Science

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