SVIBOR - Project code: 1-07-126

MINISTRY OF SCIENCE AND TECHNOLOGY

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Project code: 1-07-126


IMMUNE RESPONSE AGAINST VIRAL ANTIGEN IN IMMUNE COMPLEX


Main researcher: POKRIĆ, BISERKA (37830)



Assistants
Type of research: basic
Duration from: 01/01/91. to 12/31/96.

Papers on project (total): 5
Institution name: Institut "Ruđer Bošković", Zagreb (98)
Department/Institute: Center for marine research - Zagreb
Address: Bijenička 54
City: 10000 - Zagreb, Croatia
Communication
Phone: 385 (0)1 425-459
Fax: 385 (0)1 425-497
E-mail: pokric@olimp.irb.hr

Summary: BACKGROUND AND PURPOSE: Vaccination is still the best way for prevention of viral diseases. Undesirable side-effects, accompanying vaccines prepared from whole viruses, are avoided by the use of the antigenic viral subunits. Viral subunits are mainly poor immunogens. Antigen bound in an immune complex (IC) with specific antibodies elicts an enhanced immune response rather than antigen alone. RESULTS: The methods and techniques for identification and analysis od viruses and viral antigenic subunits and specific virus-neutralizing antibodies are developed and applied. The conditions for the preparation of the viral antigens of intact natural composition and conformation, were determined. The conditions for the IC preparation at equivalence were found. It was proved that antigen (HSA) bound at equivalence to the specific antibodies in IC, elicited enhanced humoral and cellular immune responses rather than free antigen. A better understanding of the mechanism of immune responses against an antigen in IC, contributes to a more rational design of subunit vaccines based on ICs. An IC, composed of antigenic subunits of Newcastle disease virus (NDV) and specific polyclonal chicken antibodies, was prepared. The NDV is used as a model for the preparation of vaccines based on ICs, since it belongs to a wide-spread family of enveloped viruses causing numerous human and animal diseases. Laboratory and field experiments, using chickens as experimental animals, proved that a very low quantities of the viral material in the IC generated protective level of the specific antibodies and the protection against infection. The efficiency of numerous viral vaccines, especially those used for the poultry protection and composed of the viral particles as well as viral subunits, was simultaneously determined. CONCLUSIONS: Pure viral subunits of molecularly defined composition can be easily prepared by binding to the specific antibodies in ICs. The IC vaccines represent a progress towards safe and ecologically convenient vaccine and provide a modern orientation to the use of combined vaccines. Our results and literature data agree that viral antigens coupled to specific antibodies are efficiently presented to the immunological system thus eliciting an enhanced immune response.

Keywords: chicken immune response, immune complex, murine immune response, Newcastle disease virus, protective immunity, subunit vaccines, viral antigenic subunits, viral vaccines

Research goals: The aims of this work are: (i) the studies of humoral and cellular immune responses against antigens and viral antigenic subunits bound in the IC and the role of the IC in the defense against "non-self", (ii) comparison of humoral and cellular immune responses as well as efficiency of immune protection against viruses generated by viral subunits bound in IC, free subunits and whole viral particles, (iii) comparison of humoral and cellular immune responses and efficiency of immune protection against viral infection generated by viral antigenic subunits coupled to specific antibodies in IC and viral antigenic subunits inoculated in appropriate adjuvants. These studies, together with our results showing the enhanced immune responses triggered by antigen in IC, may lead to the development of a new generation of vaccines. Vaccination is the only efficient way of preventing of viral diseases. The best immune protection is generated by vaccines containing inactivated or attenuated viruses. However, their application could be accompanied with undesirable side-effects. So far, attenuated vaccines are environmentally inconvenient. For these reasons, the vaccines containing antigenic viral subunits instead of viral particles were introduced. The poor immunogenicity of subunit vaccines is the barrier of widespread use of them. Our studies confirm that viral subunits coupled to the specific antibodies in an insoluble IC, without addition of adjuvants or immune stimulators, elicit the appropriate immune responses and anti-viral protection. The IC is environmentally safe and does not generate undesirable side-effects. Simultaneously with the poultry vaccines, other animal (rabies) or human anti-viral vaccines based on ICs, may be developed. In this case, new technology in vaccine production can be designed and introduced.

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Last update: 10/05/95
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