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1.
Gene Ther ; 21(7): 645-52, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24830436

RESUMO

The use of DNA to deliver vaccine antigens offers many advantages, including ease of manufacture and cost. However, most DNA vaccines are plasmids and must be grown in bacterial culture, necessitating elements that are either unnecessary for effective gene delivery (for example, bacterial origins of replication) or undesirable (for example, antibiotic resistance genes). Removing these elements may improve the safety profile of DNA for the delivery of vaccines. Here, we describe a novel, double-stranded, linear DNA construct produced by an enzymatic process that solely encodes an antigen expression cassette, comprising antigen, promoter, polyA tail and telomeric ends. We compared these constructs (called 'Doggybones' because of their shape) with conventional plasmid DNA. Using luciferase-expressing constructs, we demonstrated that expression levels were equivalent between Doggybones and plasmids both in vitro and in vivo. When mice were immunized with DNA constructs expressing the HIV envelope protein gp140, equivalent humoral and cellular responses were induced. Immunizations with either construct type expressing hemagluttinin were protective against H1N1 influenza challenge. This is the first example of an effective DNA vaccine, which can be produced on a large scale by enzymatic processes.


Assuntos
DNA/genética , Vetores Genéticos/administração & dosagem , Hemaglutininas Virais/imunologia , Infecções por Orthomyxoviridae/imunologia , Plasmídeos/genética , Vacinas de DNA/genética , Produtos do Gene env do Vírus da Imunodeficiência Humana/imunologia , Animais , Células CHO , Cricetulus , DNA/imunologia , Cães , Feminino , Vetores Genéticos/imunologia , Hemaglutininas Virais/genética , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H1N1/fisiologia , Células Madin Darby de Rim Canino , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/virologia , Plasmídeos/imunologia , Poli A/genética , Regiões Promotoras Genéticas , Telômero/genética , Vacinação , Vacinas de DNA/imunologia , Produtos do Gene env do Vírus da Imunodeficiência Humana/genética
2.
Mucosal Immunol ; 11(1): 249-256, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28537249

RESUMO

Tissue resident memory T (Trm) cells act as sentinels and early responders to infection. Respiratory syncytial virus (RSV)-specific Trm cells have been detected in the lungs after human RSV infection, but whether they have a protective role is unknown. To dissect the protective function of Trm cells, BALB/c mice were infected with RSV; infected mice developed antigen-specific CD8+ Trm cells (CD103+/CD69+) in the lungs and airways. Intranasally transferring cells from the airways of previously infected animals to naïve animals reduced weight loss on infection in the recipient mice. Transfer of airway CD8 cells led to reduced disease and viral load and increased interferon-γ in the airways of recipient mice, while CD4 transfer reduced tumor necrosis factor-α in the airways. Because DNA vaccines induce a systemic T-cell response, we compared vaccination with infection for the effect of memory CD8 cells generated in different compartments. Intramuscular DNA immunization induced RSV-specific CD8 T cells, but they were immunopathogenic and not protective. Notably, there was a marked difference in the induction of Trm cells; infection but not immunization induced antigen-specific Trm cells in a range of tissues. These findings demonstrate a protective role for airway CD8 against RSV and support the need for vaccines to induce antigen-specific airway cells.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Pulmão/imunologia , Infecções por Vírus Respiratório Sincicial/imunologia , Vírus Sinciciais Respiratórios/fisiologia , Sistema Respiratório/imunologia , Vacinas Virais/imunologia , Transferência Adotiva , Animais , Células Cultivadas , Feminino , Humanos , Memória Imunológica , Interferon gama/metabolismo , Pulmão/virologia , Camundongos , Camundongos Endogâmicos BALB C , Sistema Respiratório/virologia , Fator de Necrose Tumoral alfa/metabolismo , Vacinação , Vacinas de DNA , Carga Viral
3.
Mucosal Immunol ; 11(1): 290, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28853440

RESUMO

This corrects the article DOI: 10.1038/mi.2017.46.

5.
J Hyg (Lond) ; 70(1): 113-9, 1972 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-4501832

RESUMO

After the appearance of sporadic cases of enteritis due to Salmonella panama, baked ham from one supplier was implicated as the source of infection. No pathogenic organisms were isolated from the working surfaces of the factory involved or from samples of a day's bacon output, but S. panama was isolated from the factory sewers. Stool examinations of the 500 employees showed one man in the baked ham section to be excreting S. panama. He was removed from work and no further infections were reported from the district. The organism could no longer be found in the sewers.Some weeks later, further infections were reported in the London and Southend areas, which could be traced to ham from the original source. Sewer swabs at the factory were again positive. A further examination of all the employees revealed three cases and 82 symptomless excretors. Eight of 192 family contacts were also found to be excretors. Trimethoprim-sulphamethoxazole appeared to have no effect on the carrier state.Examination of the hams in cold store showed some to be infected with S. panama, and a number of these had been consumed in the canteen.Subsequent examination of pigs at slaughter and pig food prepared locally failed to isolate S. panama. The source of infection at the factory is unknown.


Assuntos
Enterite/etiologia , Carne , Intoxicação Alimentar por Salmonella , Ração Animal , Animais , Portador Sadio/tratamento farmacológico , Fezes/microbiologia , Microbiologia de Alimentos , Conservação de Alimentos , Humanos , Masculino , Salmonella/efeitos dos fármacos , Esgotos , Sulfametoxazol/uso terapêutico , Suínos , Trimetoprima/uso terapêutico
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