Mechanism of protection against influenza A virus by DNA vaccine encoding the hemagglutinin gene
| Autor: | E. Operschall, Karin Mölling, Jovan Pavlovic, M. Nawrath |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Pore Forming Cytotoxic Proteins
Hemagglutinin (influenza) Hemagglutinin Glycoproteins Influenza Virus medicine.disease_cause Antigenic drift DNA vaccination chemistry.chemical_compound Mice Orthomyxoviridae Infections Virology Influenza A virus medicine Vaccines DNA Animals Gene Mice Knockout Membrane Glycoproteins biology Perforin Granulocyte-Macrophage Colony-Stimulating Factor Interleukin-12 Mice Inbred C57BL Infectious Diseases chemistry Immunization Immunoglobulin M Influenza Vaccines biology.protein Neuraminidase DNA Plasmids |
| Zdroj: | Intervirology. 43(4-6) |
| ISSN: | 0300-5526 |
| Popis: | Influenza A virus with its two major antigenic surface proteins hemagglutinin (HA) and neuraminidase (NA) is a widely used model to study DNA immunizations in mice and other animals. Natural protection against influenza A virus infection is mediated by antibodies, which mostly are not protective against antigenic shift or drift variants of the original virus. Therefore, it would be a major task to induce a protective cellular immune re- sponse to more conserved proteins or epitopes. Injection of plasmid encoding a viral antigen is known to induce cellular as well as humoral immunity. In this study we investigate the mechanism of protection after intramuscular vaccination of C57Bl/6 mice with a DNA vaccine encoding HA of influenza A/PR/8/34. After a single injection, only a small percentage of mice survive the lethal challenge with homologous virus. The amount of protection can be doubled by applying a booster injection. Furthermore, by coinjection of plasmids encoding cytokines GM-CSF and IL-12, respectively, nearly all of the mice are protected. Mice with specific defects in the cellular immune response [perforin knockout (P–/–) mice] and in the humoral immune response [IgD/IgM knockout (µMT) mice], respectively, have been immunized with HA DNA with or without cytokine DNA. Protection could only be induced in P–/– mice, whereas µMT mice succumbed to the infection. Moreover, when µMT mice were infected with only 0.75 ×50% lethal dose they died all the same, whereby mice that had been depleted of CD8+ T cells before infection showed an even greater progression of illness. Altogether these results demonstrate that antibodies mediate protection after immunization with plasmid coding for HA of influenza A virus, and that booster immunizations and coinjection of plasmids encoding GM-CSF or IL-12 can improve this protection. |
| Databáze: | OpenAIRE |
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