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A DNA immunization model study with constructs expressing the tick-borne encephalitis virus envelope protein E in

J H Aberle¹, S W Aberle, S L Allison

¹Institute of Virology, University of Vienna, Austria.

Journal of Immunology (Baltimore, Md. : 1950)

|December 10, 1999

Summary

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DNA immunization with a secreted subviral particle construct elicited a superior immune response and protection against tick-borne encephalitis virus. The antigen

Area of Science:

Immunology
Virology
Molecular Biology

Background:

Understanding how antigen (Ag) structure and secretion impact immune responses is crucial for vaccine development.
Tick-borne encephalitis virus (TBEV) envelope glycoprotein E is a key target for neutralizing antibodies.

Purpose of the Study:

To investigate the influence of physical structure and secretion of expressed TBEV glycoprotein E on the immune response.
To compare different plasmid constructs encoding various forms of glycoprotein E for DNA immunization.

Main Methods:

Generated plasmid constructs encoding secreted subviral particles, soluble homodimers, and nonsecreted forms of TBEV glycoprotein E.
Immunized mice via intramuscular (i.m.) injection and Gene Gun delivery.
Assessed functional immune responses by measuring neutralizing and hemagglutination-inhibiting antibody activities, IgG subclasses, and cytokine induction (IFN-gamma, Il-4, Il-5).

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Main Results:

The plasmid encoding a secreted subviral particle demonstrated superior antibody response and protection against lethal TBEV challenge.
Antigen properties significantly influenced the type of T helper (Th) cell response, in addition to the mode of application.
The particulate antigen construct partially mitigated the Th2-biasing effect of Gene Gun delivery, promoting a balanced Th1/Th2 response.

Conclusions:

The physical structure and presentation of an antigen, particularly in a particulate form, significantly enhance DNA vaccine efficacy.
Optimizing antigen design can modulate the T helper cell balance, leading to more effective immune responses.
Secreted subviral particles represent a promising platform for developing subunit vaccines against flaviviruses like TBEV.